Table 3 Prevalence of Antibiotic Resistance Among Common Gram-Negative Bacteria 434 Dhawan Percent resistant to tested antibiotics Microorganism Ampicillin Gentamicin Trimethoprim- -clavulanic sulfamethoxazole Ciprofloxacin Ampicillin acid Cefazolin Cefotaxime Ceftazidime Imipenem Escherichia coli 40 5 3–17 — 0–3 0–1 0–6 2–27 0–5 Enterobacter NA 0–17 4–22 0–13 NA NA 20–42 20–42 0–2 cloacae NA 4–59 Pseudomonas inducible inducible NA 0–39 aeruginosa NA NA NA 5–27 4–28 NA 7–36 Serratia — 0–15 NA NA 0–35 ESBL 0-18 0–19 0–19 0–22 marcescens Klebsiella — 3–25 — 0–19 0 6–48 0–11 pneumoniae Abbreviations: NA, Not applicable; ESBL, Extended spectrum -lactamases. Source: Ref. 25.
Gram-Negative Bacteria 435 Table 4 Global Antimicrobial Resistance Survey of Attendees at 1998 ICAAC Meetings* Percent healthcare providers who had seen Ն 5 patients with infection Continent ESBL-producing Difficult to treat gram-negative Acinetobacter spp bacilli Asia 83% 100% Africa 71% 71% Europe 50% 16% North America 54% 46% South America 91% 100% * Attendees at the 1998 Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) Antimicrobial Resistance Symposium who had seen more than five infections caused by antibiotic-resistant gram- negative bacteria in the preceding year. Source: Ref. 82. (ICUs) in the United States (35). Teaching hospitals have been shown to have a higher prevalence of resistant organisms (10). Among these ICU patients, ESBL- producing K. pneumoniae are isolated primarily from those with urinary tract in- fections (UTIs) (50%), whereas 15% are recovered from those with bloodstream infections (36,37). Rates of ceftazidime resistance of 34% and 21% for Enter- obacter spp and P. aeruginosa, respectively, have been recently reported in U.S. ICUs (35). Organisms producing AmpC frequently are associated with infections in the ICU, representing 8% of ICU-related pneumonia isolates, 11% of UTI isolates, and 4% central line-associated bacteremia isolates. As a group, AmpC-producing organisms may represent more than 30% of isolates in ICU patients with pneu- monia in some institutions (38). As many ICU patients are elderly, and some pa- tients may eventually be transferred to an LTCF, those resistant pathogens can be expected to become an important infection control issue in this setting. C. Risk Factors Several studies have evaluated the risk factors for colonization and infection with antibiotic-resistant pathogens in nursing home residents. These risk factors in- clude poor functional status, prior antibiotic use, presence of wounds (such as pressure ulcers), and presence of foreign bodies (such as urinary catheters) (24).
436 Dhawan Table 5 Factors Associated with Increased Antimicrobial Resistance in Gram-Negative Bacteria 1. Antibiotic use 2. Prolonged hospitalization 3. Stay in intensive care unit 4. Severely ill patient status 5. Immunocompromised status 6. Use of intravenous catheters 7. Ineffective infection control 8. Interhospital transfer of patients colonized with antibiotic- resistant organisms Risk factors for acquisition of ESBLs are generally similar to those reported for other hospital-acquired organisms (Table 5). Exposure to antibiotics in general, and to ceftazidime and aztreonam in particular, has been associated with increased prevalence (32,39). Emergence of ESBL has also been associated with use of other third-generation cephalosporins (32,40–42) and exposure to trimethoprim- sulfamethoxazole (TMP-SMX) (32). Other risk factors include mechanical venti- lation, emergency abdominal surgery, the presence of percutaneous devices, longer hospital stay, and increased patient morbidity (33,41,42). II. CLINICAL INFECTIONS Gram-negative bacilli are common causes of a variety of infections in hospitals and LTCFs. Therefore, the development of resistance in these organisms is wor- risome. Extended-spectrum -lactamase-producing organisms have been impli- cated in a broad range of clinical syndromes. Escherichia coli is the most common gram-negative pathogen associated with nosocomial infections, isolated from 12% of such infections. It is the leading cause of UTIs in nursing home popula- tions (43) and among residents with nosocomial urinary tract infections, repre- senting 24% of pathogens isolated (44). Klebsiella pneumoniae is also common, representing 5% of nosocomial infection site isolates, and 8% of hospital-acquired UTI and pneumonia isolates (44). Pseudomonas aeruginosa has been associated with 9% of all hospital-acquired infection site isolates and is the most common cause of nosocomial gram-negative pneumonia, representing 17% of isolates. En- terobacter spp represents 6% of all hospital-acquired isolates and 11% cases of pneumonia isolates (44). Stenotrophomonas maltophilia (formerly Xanthomonas maltophilia) is a gram-negative bacillus that has been associated with bacteremia, respiratory tract infections, skin and soft-tissue infections, and endocarditis (45). Acinetobacter, a gram-negative coccobacillus, has emerged as an important noso-
Gram-Negative Bacteria 437 cominal pathogen. The most common site of isolation is the respiratory tract. Hos- pital outbreaks are often related to contaminated respiratory equipment (46,47). Acinetobacter also has been associated with other types of nosocomial infection, including bloodstream, soft tissue, urinary tract infections, abdominal infections, meningitis, and endocarditis. Patients with impaired host defenses or central ve- nous lines and patients in the ICU are particularly susceptible (46,48). Burkholde- ria cepacia (formerly Pseudomonas cepacia) is an uncommon cause of infections. This organism has been reported in isolated patients with pneumonia, bacteremia, and invasive otitis. It is an important opportunistic agent of pneumonia in patients with cystic fibrosis (49) and can cause life-threatening infections in patients with chronic granulomatous disease (50). III. DIAGNOSTIC APPROACH The laboratory diagnosis of ESBL-producing gram-negative bacilli requires spe- cial methods. Simple screening for ceftazidime or aztreonam resistance is not ad- equate and misses approximately 15% to 20% of ESBL-producing organisms (31). Some ESBL-containing bacteria might display in vitro susceptibility to these antibiotics, their minimum inhibitory concentrations (MIC) often are at the bor- derline of susceptibility, and the inoculum effect may lead to treatment failure in the presence of high in vivo bacterial concentrations. Resistance to cefpodoxime has been studied as a screening method. Using sensitivity breakpoints of 2g/mL or higher by MIC or less than 22 mm by disk diffusion (for a 30-ug cefpodoxime disk) has a sensitivity of 98% or more for ESBL detection (20,51). Extended-spectrum -lactamases are susceptible in vitro to -lactamase inhibitors such as clavulanic acid. The most effective way to detect ESBLs is to test for synergy between ceftazidime or cefotaxime and clavulanic acid and is recommended by the National Committee for Clinical Laboratory Standards for confirmation of ESBLs. Disks containing cefotaxime and ceftazidime alone and disks containing the combination of clavulanic acid with these antibiotics are placed on Mueller-Hinton agar. A 5 mm or greater increase in size of the zone diameter for either cefotaxime or ceftazidime tested in combination with clavu- lanic acid versus the zone for either antibiotic tested alone indicates the presence of an ESBL (10,52). An effective screening strategy might be a cefpodoxime screen followed by the confirmatory double-disk diffusion test for isolates screening positive. The Vitek ESBL test is a reliable single-test alternative. It is an automated broth microdilution test using cefotaxime and ceftazidime alone and in combina- tion with clavulanic acid. The test has been shown to be both sensitive (Ն99.5%) and specific (100%) for the detection of ESBLs (53,54). The E-test method, which involves testing third-generation cephalosporins with and without a -lactamase
438 Dhawan inhibitor, is another method. However, the test is relatively expensive and the re- liability of the commercially available version of this test is questionable (10,55). IV. THERAPEUTIC INTERVENTIONS The rapidly evolving antimicrobial resistance in gram-negative bacilli poses a sig- nificant therapeutic challenge, and multiresistance is of particular concern. The el- derly patients infected with multiresistant organisms are at higher risk for death. Patients with ESBL-producing K. pneumoniae or E. coli bacteremia are signifi- cantly more likely to survive if they receive appropriate therapy within 3 days of the onset of infection (39). Appropriate therapy of infections caused by antibiotic- resistant gram-negative bacilli is, therefore, critical to patient survival. Currently available treatment options for the common antibiotic-resistant gram-negative bacteria are summarized in Table 6. The ESBL-producing K. pneumoniae and E. coli strains are often resistant to quinolones and aminoglycosides, leaving few therapeutic alternatives. In one study, ceftazidime-resistant isolates were resistant to gentamicin and ciprofloxacin in 67% and 45% of cases, respectively, compared with rates of 3.6% and 2.0% for ceftazidime-susceptible organisms (56). For sus- ceptible isolates, however, aminoglycosides and quinolones remain effective treatment options. Carbapenems are highly effective in the treatment of bacteria- containing ESBLs, with susceptibility rates ranging from 93% to 100% (56–58). Gram-negative bacilli producing AmpC may initially test as “susceptible” to third-generation cephalosporins, but resistance can emerge during treatment with these antibiotics. It is important for the clinician to realize that even when these or- ganisms display in vitro susceptibility to the third-generation cephalosporins, treat- ment failures often occur in vivo (10,59). In one study, 20% of bloodstream iso- Table 6 Treatment Options for Antibiotic-Resistant Gram-Negative Bacilli Organism Potential treatment options ESBL-producing Klebsiella, Imipenem or meropenem, cefepime, quinolones (for Escherichia coli susceptible strains) Enterobacter spp Imipenem or meropenem, cefepime, quinolones Pseudomonas aeruginosa Imipenem or meropenem, cefepime Stenotrophomonas Trimethoprim/sulfamethoxazole, ticarcillin-clavulanic maltophilia acid, quinolones Acinetobacter spp Imipenem Burkholderia cepacia Trimethoprim/sulfamethoxazole Abbreviation: ESBL, Extended-spectrum beta-lactamase.
Gram-Negative Bacteria 439 lates of E. cloacae developed resistance to third-generation cephalosporins upon exposure to these agents (60). In contrast to other cephalosporins, cefepime, a new aminothiazolylacetamido, has a wider spectrum and a greater potency against the ESBL-producing organisms. Cefepime penetrates the gram-negative cell more rapidly, targets multiple essential penicillin-binding proteins, and escapes the ef- fects of many -lactamases because of the enzymes’ low affinity for the drug (61). Cefepime is a much weaker inducer of AmpC production. The latter characteristic is most apparent in studies of Bush group 1 -lactamases. Derepression of this class of -lactamases has lesser effect on the in vitro activity of cefepime as compared with other cephalosporins. In one study, 80% of Pseudomonas isolates and more than 99% of other AmpC-producing Enterobacteriaceae tested sensitive to ce- fepime (57). The carbapenems represent another treatment option. Eight-four per- cent of Pseudomonas isolates and more than 99% of Enterobacter and Citrobac- ter isolates remain sensitive (57). Cephamycins are a treatment option, but plasmid-mediated AmpC -lactamase production and porin channel mutations may limit their clinical utility (10). Quinolones and aminoglycosides are often ef- fective, although resistance is emerging (62,63). Ceftibuten, an oral oxyimino- lactam that binds less tightly to ESBLs than other cephalosporins, has demon- strated reasonable in vitro activity, but clinical experience with this antibiotic is limited (64). -Lactam/-lactam inhibitor antibiotics have good in vitro activity against some ESBL-expressing organisms (65) and have been shown to protect against ESBL acquisition (66). However, bacterial mutation may lead to increased susceptibility to these agents. AmpC is not susceptible to -lactamase inhibitors. Because of the high prevalence of antibiotic resistance, and because of the poten- tial for emergence of resistance during therapy, Pseudomonas infections are usu- ally treated with two active agents. The management of infections caused by S. maltophilia is problematic, be- cause many strains manifest resistance to multiple antibiotics. Trimethoprim-sul- famethaxazole is the treatment of choice for infections due to S. maltophilia. Ticarcillin-clavulanate is the only -lactam/-lactam inhibitor combination an- tibiotic that is reliably effective in the treatment of S. maltophilia. It has been sug- gested as the treatment of choice for patients who are unable to tolerate TMP- SMX (45). Resistance to both of these agents is, however, increasing (67,68). Aminoglycosides generally are not active against S. maltophilia, possibly because of aminoglycoside-mediating enzymes and alterations in cell surface (45). Resis- tance rates to imipenem approach 100% (46). Cefepime has greater in vitro activ- ity against S. maltophilia than does ceftazidime, with susceptibility rates of blood- stream isolates reported to be 88.7% and 35.3%, respectively, in one U.S. study (47). Some of the newer quinolones, notably clinafloxacin, sparfloxacin, and trovafloxacin, have better in vitro activity than ciprofloxacin (68–70). In one study, 94% of isolates were susceptible to clinafloxacin (69). Minocycline has good in vitro activity (68), but its use in clinical settings is limited. Antibiotic com-
440 Dhawan binations, such as TMP-SMX and either ticarcillin/clavulanate or a third-genera- tion cephalosporin or minocycline might be more appropriate in the treatment of serious S. maltophilia infections (68,71). Acinetobacter infections are most reliably treated with carbapenems, al- though resistance to these agents is emerging (48,57). Quinolones may be effec- tive treatment options for some strains. One study noted that only 17% of clinical A. baumannii isolates were susceptible to this antibiotic class (48). Aminoglyco- side resistance is common in A. baumannii, occurring in approximately 85% of isolates (48). -Lactam/-lactamase antibiotics have good in vitro activity against A. lwoffi (Ͻ10% are resistant) but are less effective against A. baumannii, with 30% of strains being resistant. Ceftazidime and cefepime are active against A. lwoffi, but have lesser activity against A. baumannii; resistance rates approach 12% and 30%, respectively, in the two isolates (48,58). Intrinsic resistance of B. cepacia to several antibiotics complicates treat- ment of infections caused by this organism. Trimethoprim-sulfamethoxazole has historically been the drug of choice. Ceftazidime, meropenem, and ciprofloxacin are also active for most of the strains. V. INFECTION CONTROL MEASURES Nursing home residents may be an important reservoir of multiple antibiotic-re- sistant organisms, including ESBL-producing gram-negative bacteria. There has been little evaluation of methods to limit the spread of infections in the nursing home population. Most of the recommendations are extrapolated from programs considered effective in acute care facilities. The role of ESBL-producing organ- isms in hospital and nursing home outbreaks, as well as the ability of their plas- mid DNA to be transferred to other bacterial species, makes effective control a growing challenge. Nursing home outbreaks can occur through either clonal spread of a specific plasmid-carrying strain or transfer of a particular plasmid to a variety of bacterial strains or even different bacterial genera (33,72,73). Use of broad-spectrum antibiotics and poor infection control practices facilitate the spread of this plasmid-mediated resistance. Efficient monitoring of antimicrobial resistance can produce timely and im- portant data and information. One of the reasons cited for the spread of the organ- ism in the largest outbreak of ESBL-producing K. pneumoniae, which occurred at a Brooklyn, New York hospital, was missed initial detection. Implementation of effective screening methods for the detection of ESBLs is a key factor in the con- trol of hospital outbreaks and is necessary for accurate surveillance. Resistant or- ganisms can be passed from patient to patient by the hands of healthcare providers (74). A recent outbreak of Enterobacter aerogenes in a geriatric acute unit was at- tributed to the failure to institute contact isolation (75). Patients infected or colo-
Gram-Negative Bacteria 441 nized with antibiotic-resistant bacteria, including ESBL-producing gram-negative bacteria, should be isolated and barrier precautions instituted to prevent the spread of these organisms in the LTCFs. Transient limitation of resident movement and interaction within the facility and specific therapy for antibiotic-resistant bacterial infections are important control measures. Appropriate planning for identifying, transferring, discharging, and readmitting residents with antibiotic-resistant gram- negative bacilli to LTCFs constitute important control measures. Restriction of cephalosporin use has been associated with control of hospi- tal outbreaks (32,76,77). Class restriction of all cephalosporins at a New York hos- pital was associated with significant reduction in the prevalence of ceftazidime-re- sistant K. pneumoniae (77). Unfortunately, there was a significant increase in imipenem-resistant P. aeruginosa during the study period, presumably related to increased use of imipenem. Discontinuation of ceftazidime use at a hospital in Mas- sachusetts resulted in a significant decrease in the prevalence of ESBL-producing K. pneumoniae. Education of healthcare providers, application of clinical practice guidelines, and audit and feedback activities have all been shown to have a salu- tary effect in altering antibiotic prescribing. Nursing homes should monitor and control antibiotic use and regularly survey antibiotic resistance patterns among pathogens. Pharmacists can play a major role through clinician education and fo- cused clinical services. With the cooperation of healthcare teams, the effectiveness of available antibiotics may be sustained and the threat of resistance minimized. VI. PREVENTION To control the emergence of resistant pathogens, CDC and infection control guide- lines must be adhered to. Prevention of resistance emergence and the spread of an- tibiotic-resistant gram-negative bacilli requires prudent use of antimicrobials and strict adherence to infection control measures. There is intense antimicrobial use in LTCFs, and studies have repeatedly documented that much of this use is inap- propriate (43). Attempts to improve antimicrobial use in LTCFs are complicated by characteristics of the resident population, limited availability of diagnostic tests, and the virtual absence of relevant clinical trials. Optimal use of antimicrobials is essential in the face of escalating antibiotic resistance and requires cooperation from all sectors of the healthcare system (see Chapter 11). Clinicians must alter their antibiotic prescribing habits for the treatment of infectious diseases, and pa- tients must change their perception of the need for antibiotics. Important strategies for the prevention of antimicrobial resistance with regard to antibiotic use include monitoring of antibiotic use, improving antimicrobial prescribing by educational and administrative means, optimizing perioperative prophylaxis, optimizing the choice and duration of empirical therapies, and developing guidelines for the opti- mal use of antibiotics for common indications.
442 Dhawan Cycling of currently available antibiotics to reduce resistance is an attrac- tive concept, because it periodically removes from the institutional environment certain classes or specific agents that could induce or select for resistance (78). For cycling strategies to be successful, their implementation must have a demonstra- ble impact on the prevalence of resistance determinants already dispersed throughout the patient environment. Rotational usage practices are likely to be most appropriate for drugs active against gram-negative bacilli because of the wide choices available for rotation. Antibiotic use provides an obvious stimulus for the emergence of resistance, but it is by no means the only important factor. Antibiotic recycling must be evaluated in the context of concomitant attempts to improve antimicrobial use and must take into account other factors influencing re- sistance (79). Large scale, nation-wide cooperative studies may provide data on this important issue. There has been a growing appreciation of the role played by the use of an- tibiotics in agriculture, aquaculture, and veterinary settings in the emergence of an- timicrobial resistance. For example, fluoroquinolone use in aquaculture has been associated with the emergence of a variety of gram-negative bacilli, including E. coli, Aeromonas salmonicida, and other organisms (80). Subtherapeutic concen- trations of tetracyclines have been shown to increase the frequency of the transfer of resistance plasmids in the guts of animals (81). Global control of antimicrobial resistance must also address the non-human use of antimicrobial agents. REFERENCES 1. Holmberg SD, Solomon SL, Blake PA. Health and economic impacts of antimicro- bial resistance. Rev Infect Dis 1987; 9:1065–1078. 2. Bush K, Jacoby GA, Medeiros AA. A functional classification scheme for beta-lac- tamases and its correlation with molecular structure. Antimicrob Agents Chemother 1995; 39:1211–1233. 3. Livermore DM. Beta-lactamases in laboratory and clinical resistance. Clin Microbiol Rev 1995; 8:557–584. 4. Blahova J, Hupkova-Lesicka M, Kralikova K, Krcmery V, Kubonova K, Torsova V, Bartonikova N, Schafer V. Further studies of transferable antibiotic resistance in strains of Pseudomonas aeruginosa from four clinical settings in three countries. J Chemother 1998; 10:215–220. 5. Coudron PE, Moland ES, Sanders CC. Occurrence and detection of extended-spec- trum beta-lactamases in members of the family Enterobacteriaceae at a veterans medical center: Seek and you may find. J Clin Microbiol 1997; 35:2593–2597. 6. Nordmann P, Guibert M. Extended-spectrum beta-lactamases in Pseudomonas aeruginosa. J Antimicrob Chemother 1998; 42:128–131. 7. Pitout JD, Thomson KS, Hanson ND, Ehrhardt AF, Coudron P, Sanders CC. Plasmid- mediated resistance to expanded-spectrum cephalosporins among Enterobacter aero- genes strains. Antimicrob Agents Chemother 1998; 42:596–600.
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25 Candida and Other Fungi Carol A. Kauffman University of Michigan, and Veterans Affairs Ann Arbor Healthcare System, Ann Arbor, Michigan Sara A. Hedderwick Royal Victoria Hospital, Belfast, Northern Ireland I. EPIDEMIOLOGY AND CLINICAL RELEVANCE The prominent fungal infections encountered in residents who reside in long-term care (LTCFs) facilities are local infections of skin and mucous membranes. Inva- sive fungal infections are uncommon. This is likely due to the fact that although older adults in LTCFs are chronically ill and have many underlying illnesses, most are not immunosuppressed in the classic sense. Most infections in the LTCF are caused by dermatophytes, which only su- perficially infect the skin and hair structures, and Candida species, which nor- mally colonize the gastrointestinal and genitourinary tracts of humans. Filamen- tous fungi, such as Aspergillus, are almost always acquired from the environment and cause disease in those who are immunosuppressed. The endemic mycoses, such as histoplasmosis and blastomycosis, also are acquired from the environ- ment. Because several of the endemic mycoses are known to reactivate years af- ter initial infection, these infections may rarely occur in residents of an LTCF. However, discussions of the disparate disease manifestations and treatment of the various endemic mycoses are beyond the scope of this chapter. The reader is in- stead referred to standard infectious diseases textbooks or review articles for fur- ther details regarding these infections in older adults (1,2). Systemic fungal infections are uncommon in the LTCF, but increasingly, patients are transferred to such facilities for continuation of intravenous antimi- crobial agents, including antifungal agents, initiated in the hospital. Thus, knowl- 449
450 Kauffman and Hedderwick edge of modes of administration, side effects, and drug-drug interactions of sys- temic antifungal agents will be important for the care of some residents. Because these infections are uncommon in the LTCF, the diagnosis and initiation of ther- apy for a systemic fungal infection should be undertaken only after consultation with an infectious diseases physician. A. Dermatophytes Dermatophytes normally infect the keratinized layers of the skin and the hair shafts, rarely causing invasive disease. They are responsible for tinea corporis (ringworm), tinea pedis (athlete’s foot), tinea cruris (“jock itch”), tinea capitis, and onychomycosis. The exact prevalence of dermatophyte infections in older adults is difficult to ascertain. Most authors agree that the prevalence of onychomycosis caused by dermatophytes significantly increases with age (3,4). One study noted that 30% of patients age 60 and older had onychomycosis (4). Alternatively, scalp infection is predominantly a childhood disease and rarely seen in the elderly. Al- though uncommon, outbreaks of tinea corporis have been described in residents of LTCFs (5–8). The genera of dermatophytes that cause disease in humans are Trichophy- ton, Microsporum, and Epidermophyton. Different species of dermatophytes vary in their host specificity. Many cause disease only in humans and are transmitted directly by person-to-person contact or by fomites, such as hairbrushes. Other species have specific associations with animals and can be transmitted from pets (9) (Table 1). Table 1 Epidemiology of Fungal Infections in Long-Term Care Facilities Fungal organism Pertinent epidemiologic characteristics Dermatophytes Usually single cases, men more than women, chronic, relapsing infections; rarely, outbreaks occur with spread among patients Candida and healthcare workers; potential for outbreaks of certain species (e.g., Microsporum canis) from pets brought into the Cryptococcus facility Aspergillus Zygomycoses Infection almost always from patient’s own endogenous flora, although potential for transmission exists; Candida glabrata more common in urinary tract and in older persons; infection more likely in those with indwelling intravenous and urinary catheters Acquired from outside environment; may present later as chronic meningitis or dementia in long-term care resident Acquired from outside environment; rare in LTCFs Acquired from outside environment; rare in LTCFs
Candida and Other Fungi 451 B. Yeast Infections 1. Tinea Versicolor Malassezia furfur, also known as Pityrosporum orbiculare, is the cause of tinea versicolor, a superficial fungal infection of the head, neck, and chest (10). This or- ganism is frequently part of the normal flora found on the skin of humans. Tinea versicolor occurs most often in young adults; however, it frequently recurs and is not uncommon in older adults residing in LTCFs. 2. Candida The most common systemic fungal infections in older residents are those due to Candida spp. In acute care hospitals, Candida spp. are the fourth leading cause of nosocomial bloodstream infections and are responsible for 10% of hospital-ac- quired bloodstream infections (11). However, serious Candida infections, such as candidemia, appear not to be a major problem in LTCFs; local Candida infections are much more common in the LTCF (12–15). Candida species are yeasts that are part of the normal flora that colonize the human gastrointestinal and genitourinary tracts. C. albicans is the most common colonizing species and is the cause of most infections. Candida glabrata (for- merly Torulopsis glabrata) is an important cause of urinary tract infection and candidemia in older adults (16,17). In some hospitals, the proportion of fungemias due to C. glabrata is strikingly higher in those age 60 and older (17). Candida glabrata is also disproportionately increased in the oropharynx of octogenarians compared with those who are ages 60 to 80, and is a cause of denture stomatitis (18) (Table 1). Candida parapsilosis and C. tropicalis, although found less frequently, also cause serious infection. Candida parapsilosis is strongly associated with infection of intravascular catheters (19,20), and C. tropicalis is prominent in patients with malignancies (16,20). The widespread use of antifungal agents, among other fac- tors, has contributed to the emergence of more resistant species of Candida, such as C. krusei and C. lusitaniae (20,21). However, these species appear to be more problematic in the acute care setting than in the LTCF. Risk factors and patterns of yeast colonization among residents of LTCFs have been assessed in very few studies (12,13). One study noted that 84% of res- idents of a veterans’ LTCF were colonized with yeasts on at least one occasion; overall, 42% had intermittent colonization, and 16% were persistently colonized (12). Risk factors independently associated with colonization included neurogenic bladder, lower extremity amputation, and low serum albumin concentration. Dia- betes mellitus, often considered a risk factor for Candida infections, was not as- sociated with high rates of colonization with Candida species. However, it should be noted that that study did not assess candiduria, which has been strongly asso- ciated with diabetes mellitus (22,23).
452 Kauffman and Hedderwick Most Candida infections are acquired as the result of overgrowth and sub- sequent invasion by Candida species that are indigenous to the host’s gastroin- testinal tract. For these normally commensal yeasts to become pathogenic, inter- ruption of the normal host defenses must occur. For many residents, infection begins with disruption of the gastrointestinal mucosal barrier and culminates in tissue invasion and hematogenous dissemination. Neutrophils and monocytes pro- vide the major defense against Candida species that breach the mucosal barriers. Thus, residents with severe and prolonged neutropenia are at risk for candidemia and disseminated candidiasis. This type of resident is infrequently cared for in a LTCF. Somewhat ironically, cell-mediated immunity is important in the control of growth of Candida on mucosal surfaces; thus, acquired immunodeficiency syn- drome (AIDS) patients with low CD4 cell counts suffer from recurrent oral, esophageal, and vaginal candidiasis but have no increased risk of candidemia. Some forms of mucocutaneous candidiasis in older adults are associated with di- minished cell-mediated immunity; most, however, are the result of local physio- logical changes associated with aging, such as xerostomia. 3. Cryptococcosis Infection with Cryptococcus neoformans is uncommon in the LTCF. The infec- tion is almost always acquired from the outside environment and not in the hospi- tal or nursing home. This heavily encapsulated yeast is inhaled, causing pul- monary infection, which is usually asymptomatic. Because of the organism’s neurotropism, the most common clinical manifestations of cryptococcosis are those that occur after spread to the central nervous system. Only rarely is the source and time of exposure to C. neoformans established. Development of cryp- tococcal meningitis in a resident in an LTCF is most likely the result of reactiva- tion of infection acquired years earlier. Cryptococcosis is noted most often in older adults who have been treated with corticosteroids, have received an organ transplant, or who have diabetes mel- litus, renal failure, liver dysfunction, or chronic obstructive pulmonary disease. However, approximately 20% to 30% of patients, most of whom are older, have no underlying risk factors (24). C. Invasive Filamentous Fungal Infections Aspergillus and the zygomycetes, Mucor and Rhizopus, the filamentous fungi most often implicated in human disease, are ubiquitous in the environment and grow especially well in decaying organic material. Only rarely do these fungi in- fect residents in the LTCF (Table 1). Almost always, invasive infections with these fungi occur in immunosuppressed patients, especially those who are taking
Candida and Other Fungi 453 corticosteroids and are neutropenic. However, more indolent forms of infection with Aspergillus do occur in older adults who are not immunosuppressed or have only mild immunosuppression (25,26). The zygomycetes have a propensity to cause infection in patients with diabetes mellitus complicated by ketoacidosis and in those with iron overload states that require treatment with the iron chelator, de- feroxamine (27,28). Overall, however, infections with filamentous fungi are very uncommon in the LTCF. II. CLINICAL MANIFESTATIONS A. Dermatophyte Infections 1. Tinea Corporis (Ringworm) The dermatophytes characteristically produce annular lesions that have prominent edges and contain pustules, central clearing, and scaling. Pigmented skin can be- come hyperpigmented. There may be single or multiple lesions that tend to occur on the trunk or legs. Pruritus may be present, but is often mild. The rash should be differentiated from contact dermatitis, eczema, and psoriasis. 2. Tinea Cruris This manifestation is seen almost exclusively in men. Infection usually starts with scaling and irritation in the groin and then extends to involve the anterior thighs. The rash may be unilateral or bilateral and is erythematous and pustular. Tinea cruris is commonly associated with tinea pedis, which may act as a reservoir after apparent cure. The rash must be differentiated from that of intertrigenous can- didiasis, erythrasma caused by Corynebacterium, and psoriasis, which can occa- sionally present as a rash in the groin. The absence of satellite lesions beyond the edge of the rash points toward a dermatophyte infection, rather than candidiasis, and erythrasma and psoriasis are not pustular. 3. Tinea Capitis Dermatophyte infections of the scalp vary depending on the infecting species. The main clinical appearances are scaling of the scalp skin with varying levels of ery- thema, pustules, and alopecia. Infections with species transmitted from animals often produce marked pustules. Tinea capitis is rarely seen in elderly residents. 4. Tinea Pedis This is another dermatophyte infection that is far more common in men than women. It is very common in institutions in which common bathing facilities are used. The infection usually starts in the web spaces of the lateral toes with char-
454 Kauffman and Hedderwick acteristic peeling, fissures, maceration, and pruritus. Superinfection of web space tinea pedis by bacterial pathogens may cause a sudden worsening of symptoms. The soles and lateral borders of the feet are also involved, showing erythema and scaling. Residents who have recurrent lower extremity cellulitis should be exam- ined carefully for signs of tinea pedis, as this is a frequent point of ingress of strep- tococci and staphylococci into the dermis (29). 5. Onychomycosis Fungal infection of the nail is predominantly caused by dermatophytes. Almost al- ways, persons with onychomycosis caused by dermatophytes also have chronic tinea pedis. Several clinical types of onychomycosis have been described (30,31). The most common is distal and lateral subungual onychomycosis in which the nail bed is invaded from the distal and lateral borders. The nail becomes thickened and can take on a white, yellow, or brown hue. The distal part of the nail can com- pletely crumble. In contrast to Candida nail infections, fingernails are much less commonly affected than toenails. B. Yeast Infections 1. Tinea Versicolor This benign skin infection usually presents as flat round patches of hypo or hy- perpigmented skin on the neck, chest, or upper arms. Mild pruritus may be pre- sent, and a fine scaling can be seen. The lesions should be differentiated from those associated with vitiligo, in which no scaling is present. 2. Candida Infections (Table 2) a. Oropharyngeal Candidiasis. Oropharyngeal candidiasis (thrush) is associated with a number of different local and mechanical factors (32). These factors include the use of broad-spectrum antibiotics, inhaled corticosteroids, and radiation therapy to the head and neck areas. Additionally, xerostomia, related to a variety of systemic diseases and different medications, is associated with increased colonization and infection with Candida (33,34). Age alone is not sufficient for the development of oropharyngeal candidiasis. If thrush is present in an older adult who has no obvious risk factors, the possibility of underlying immunosuppression resulting from cancer or AIDS should be explored. White plaques appear on the buccal, palatal, and oropharyngeal mucosa; these usually are not painful and can be scraped off with a tongue depressor, re- vealing erythematous mucosa. With or without oropharyngeal lesions, patients may have painful cracks at the corners of the mouth (perleche or angular cheilitis) (14,32).
Candida and Other Fungi 455 Table 2 Major Clinical Manifestations of Infection with Candida Manifestation Major characteristics Oropharyngeal White plaques on buccal mucosa, palate, tongue; under upper (thrush) dentures appears as diffuse erythema Cutaneous Erythematous, pustular, pruritic rash in warm moist areas; (intertrigo) satellite lesions beyond primary border common Onychomycosis Thickened, opaque nails with onycholysis Vulvovaginitis Erythema, white exudate, and discharge; vulvar pruritus Urinary tract Lower tract infection - dysuria, increased frequency Upper tract infection - fever, flank pain, nausea, vomiting infection Fungus ball may form and obstruct collecting system Fever, chills, hypotension, tachycardia,“toxic” appearance Candidemia Pustular skin lesions, retinal lesions, vitritis Depends on organ involved - includes osteoarticular infections, Invasive candidiasis endocarditis, meningitis, hepato-splenic candidiasis Denture stomatitis (chronic atrophic candidosis) is a variant of oral candidi- asis that has been noted in as many as 65% of residents who wear dentures and oc- curs particularly in those with full upper dentures (35). Lower dentures are rarely linked to the development of candidiasis. Residents who have poor oral hygiene and who do not remove their dentures at night are more likely to develop this form of oropharyngeal candidiasis. Plaques are rarely observed under the dentures; more often, diffuse erythema is seen on the hard palate when upper dentures are removed. Residents may be asymptomatic, but often complain of pain and irrita- tion associated with their dentures. b. Candida Infections of the Skin and Nails. Candida infection of the skin (in- tertrigo) occurs mostly under pendulous breasts or pannus and in the perineum. The erythematous, pruritic, frequently pustular lesions have a distinct border; smaller satellite lesions provide a clue to the diagnosis of candidiasis. However, scratching may distort the typical lesions and make the diagnosis more difficult. The main dif- ferential diagnosis is tinea cruris or tinea corporis resulting from dermatophytes. Most cases of onychomycosis are caused by dermatophytes; however, Can- dida also can infect the nails, especially those of the hand. The nails become thick- ened, opaque, and wrinkled, the condition may be painful, and onycholysis is fre- quent (36). Older adults with diabetes mellitus can have serious consequences from onychomycosis. The thickened nails are difficult to trim, predisposing these residents to trauma and subsequent bacterial infections, such as paronychia and cellulitis. Candida can also cause paronychia; this occurs most often in those whose occupation involves frequent immersion of their hands in water and is an unlikely infection among residents in a LTCF.
456 Kauffman and Hedderwick c. Vulvovaginitis. Candida vulvovaginitis is not increased in older women. After menopause, Candida vulvovaginitis actually becomes less common. This decrease is likely related, at least in part, to the estrogen dependence of Candida vaginal epithelial colonization (37). Estrogen replacement therapy to prevent menopausal vasomotor symptoms, osteoporosis, and heart disease increases vagi- nal Candida colonization but has not been associated with an increase in vulvo- vaginitis in older women. Among older women with Candida vulvovaginitis, risk factors include diabetes mellitus, corticosteroid therapy, and broad-spectrum an- tibiotic therapy (38). Episodes of vaginitis may recur with intermittent antibiotic therapy. Candida vulvovaginitis is manifested as vulvar pruritus, vaginal discomfort, and discharge; classically, the discharge is described as curdlike, but it can also be thin and watery. External burning is experienced with urination. The labia are of- ten erythematous and swollen; the vaginal walls show erythema, and white plaques and discharge usually are evident. d. Candida Urinary Tract Infections. Candiduria is a frequent finding in resi- dents of LTCFs. Factors predisposing to candiduria include diabetes mellitus, the use of broad-spectrum antibiotics, the presence of an indwelling urinary catheter, and genitourinary tract abnormalities (22,23,39,40). Most residents with candiduria are asymptomatic and probably do not have infection, but merely colonization. Residents with lower urinary tract infection can have symptoms similar to those seen with bacterial cystitis: suprapubic discomfort, dysuria, and frequency. Those who have upper urinary tract infection may present with fever, flank pain, nausea, and vomiting, these symptoms are indistinguishable from acute bacterial pyelonephritis. Uncommonly, a fungus ball composed of fun- gal hyphae may form and obstruct the collecting system at any level. e. Systemic Candida Infections. Risk factors for infection in older adults include broad-spectrum antibiotics, indwelling urinary and central vascular catheters, hy- peralimentation, renal failure, and surgical procedures involving the gastrointesti- nal (GI) tract (41,42). In the LTCF, a group of residents at high risk for candidemia are those who are receiving hemodialysis. Immunosuppressive drugs, increasingly used for residents with dermatologic and rheumatologic conditions, also can con- tribute to the risk for development of systemic candidiasis when they cause neu- tropenia. The attributable mortality from candidemia approaches 38% (42) and ap- pears to be higher in the elderly population (43). Candidemia is the most obvious manifestation of serious infection with Candida species, but patients may have septic shock or organ invasion without positive blood cultures. The patient with candidemia often appears “toxic,” and the clinical presentation cannot be distin- guished reliably from that caused by bacteremia. Clinical clues to the diagnosis of candidemia include the appearance of skin and retinal lesions. The skin lesions are
Candida and Other Fungi 457 papular to pustular, have a small zone of surrounding erythema, and are not painful or pruritic. The retinal lesions appear as white exudates that can extend into the vitreous and obscure the retina. The presence of yeast in the urine is as- sociated with both hematogenous spread and ascending urinary tract infection, and thus is not a helpful sign in the diagnosis of candidemia, especially in a pa- tient with an indwelling urethral catheter. Once bloodstream invasion has oc- curred, the development of microabscesses in many organs is common. The eyes, kidneys, liver, spleen, brain, and bones are the most commonly involved sites. 3. Cryptococcosis An appreciation of the clinical findings of cryptococcal meningitis is important, as this is a treatable cause of mental status changes in older adults. Cryptococco- sis typically presents as subacute meningitis, but in older persons, mental status changes without fever, headache, or focal neurological findings may be the only manifestation (44,45). Isolated pulmonary cryptococcosis occurs more often in older adults than their younger counterparts (24,46). A recent retrospective review of 316 patients who did not have concomitant human immunodeficiency virus (HIV) infection noted that mortality rates for patients with either meningitis or pulmonary cryptococcosis were higher for those older than age 60 (24). C. Invasive Filamentous Fungal Infections 1. Sino-Orbital Aspergillosis Older adults who develop sino-orbital aspergillosis usually are not overtly im- munosuppressed, although some have had prior corticosteroid therapy. Orbital pain and loss of vision are the most common presenting symptoms; proptosis, ophthalmoplegia, and decreased visual acuity are noted on examination. The in- fection often arises in adjacent sinuses and then extends behind the orbit entrap- ping the optic nerve; further extension into cerebral vessels and brain may occur. 2. Chronic Necrotizing Pulmonary Aspergillosis This form of aspergillosis occurs mostly in middle-aged and elderly men who have underlying chronic obstructive pulmonary disease (25). These individuals generally are not immunosuppressed, other than occasional corticosteroid ther- apy. Symptoms are those of a progressive pneumonia that is unresponsive to an- tibacterial agents and that progresses to include cavitation and pleural involve- ment. Cough productive of purulent sputum with occasional hemoptysis, pleuritic chest pain, and increasing dyspnea, as well as fever, night sweats, anorexia, weight loss, and fatigue are common. The differential diagnosis includes other fungal pneumonias, such as histoplasmosis and blastomycosis, atypical mycobac-
458 Kauffman and Hedderwick terial infections, nocardiosis, actinomycosis and, less commonly, chronic bacte- rial pneumonias. 3. Zygomycosis (Mucormycosis) This life-threatening infection is seen rarely in the LTCF. In this setting, residents likely to develop zygomycosis are diabetics who have poor glycemic control and are prone to ketoacidosis and residents who have myelodysplastic syndromes, are transfusion-dependent, and require treatment with an iron chelator. The zy- gomycetes have a propensity to invade through blood vessels, causing infarction and necrosis (47). Residents present with rapidly progressive painful necrotic le- sions of the palate, nares, sinuses, or orbit. If this diagnosis is suspected, the resi- dents must be transferred immediately to an acute care hospital for diagnosis and treatment. III. DIAGNOSTIC APPROACH A. Localized Mucocutaneous Infections 1. Skin Infections The diagnosis of most dermatophyte and cutaneous yeast infections is made by clinical appearance. However, if no improvement is noted within 1 to 2 weeks of initiating local therapy or if the lesions are extensive enough to warrant systemic therapy, microscopic examination of scrapings from the lesion should be per- formed. This will ensure that noninfectious causes of rash are not treated inap- propriately and that the appropriate antifungal agent is used for treatment. Scrap- ings should be taken from the edge of the lesion with a scalpel blade, collected on a piece of dark paper, and transferred to a slide, on which is added a drop of potas- sium hydroxide (9). Microscopic examination reveals hyphae in cases of der- matophyte infection and yeast when Candida or Malessezia is the cause of the in- fection. If there is a suspicion of an outbreak of dermatophyte infections or of a possible animal source of the infection, then skin scrapings should be sent for cul- ture (in a paper packet, not in a culture transport tube as used for bacterial infec- tions), or consultation should be sought with a dermatologist, who can provide ad- vice and collect the appropriate samples. 2. Nail Infections For individuals with onychomycosis, full-thickness nail clippings taken as close to the nail bed as possible may show fungal elements when viewed under direct microscopy after potassium hydroxide digestion. However, for up to 50% of clin- ically diagnosed cases of onychomycoses, fungi will not be seen (48). Culture of
Candida and Other Fungi 459 the nail is especially useful for cases of onychomycosis, because treatment courses are long and not without side effects and drug-drug interactions (49). 3. Mucous Membrane Infections Oropharyngeal and vaginal candidiasis are diagnosed primarily by clinical ap- pearance. Scrapings of the exudates that are then stained with Gram’s stain or vi- sualized as a wet preparation reveal budding yeasts and, often, pseudohyphae. Cul- ture is usually not necessary unless there is a poor response to therapy or multiple recurrent episodes. In that situation, fungal culture will show whether an unusual drug-resistant species is the cause of the infection and will guide further therapy. B. Candida Urinary Tract Infections A major dilemma arises in determining whether yeasts in a urine sample represent contamination, colonization, or infection (39,40,50) (Table 3). Contamination Table 3 Approach to the Patient with Candiduria in the Long-Term Care Facility 1. Repeat culture to be sure not a contaminant. 2. If repeat culture is (ϩ) and patient is asymptomatic: –assess predisposing factors (diabetes mellitus, antibiotics, indwelling catheters, genitourinary tract abnormalities) and correct if possible –if remains asymptomatic, observe, do not treat 3. If repeat culture is (ϩ) and patient has mild symptoms suggesting lower urinary tract infection: –culture urine for bacteria and treat if found; check whether symptoms resolve –assess predisposing factors as listed above and correct if possible –bacterial infection not present, predisposing factors removed, observe clinical response and repeat urine culture to see if funguria has cleared –if remains symptomatic and funguria remains, treat with fluconazole 14 days 4. If repeat culture is (ϩ) and patient appears ill: –image the genitourinary tract to be sure no obstruction present (ultrasound, CT scan) –if obstruction present, urology consult for options to relieve obstruction –obtain blood cultures to be sure not fungemic –correct predisposing factors when possible –treat with fluconazole 14 days 5. Follow urine cultures at end of therapy, if clinical condition worsens at any time during treatment, and several weeks after therapy has ended to be certain funguria has cleared. Abbreviation: CT, Computed tomography.
460 Kauffman and Hedderwick may be detected by repeating the collection and culture of the urine. In older women, catheterization of the urethra may be needed to obtain an uncontaminated urine specimen. The difference between colonization and infection is less clearly defined. This problem has arisen, in part, because candiduria is usually an asymptomatic condition. Currently, no test on urine can differentiate Candida colonization from infection (23). The presence of a urinary catheter in most residents with candiduria limits the usefulness of pyuria. Yeast quantitation has not proved helpful in sepa- rating infection from colonization. The presence of pseudohyphae, although once thought to indicate urinary tract infection, also has not proved useful. For residents suspected of having upper tract infection, imaging studies are necessary. Ultrasonography, computerized tomography, or retrograde pyelogra- phy can be used to ascertain the presence of hydronephrosis; fungus balls are seen as masses obstructing the collecting system or filling the bladder. C. Systemic Infections 1. Candidiasis The diagnosis of candidiasis should be entertained in any resident in the LTCF who appears septic and who has any of the risk factors noted above, especially hemodialysis and presence of central intravenous catheters, for invasive candidi- asis. Blood should be cultured using the same techniques used for bacteria. A sin- gle positive culture yielding yeast is adequate for a diagnosis of candidemia. How- ever, blood cultures yield the organism in as few as 50% of cases of invasive candidiasis (51). Residents who are suspected of having systemic Candida infec- tion should be transferred to an acute care facility where further diagnostic proce- dures can be performed. 2. Cryptococcosis Residents suspected of having cryptococcal meningitis should have a lumbar punc- ture performed, including measurement of opening pressure. This will usually re- quire transfer to an acute care facility. The typical cerebrospinal fluid (CSF) find- ings are those of a lymphocytic meningitis with elevated protein and decreased glucose (24). A latex agglutination test for cryptococcal polysaccharide capsular antigen is available in most hospitals. This assay, which should be performed on both CSF and blood, is very sensitive and specific for cryptococcal infection. Cul- tures of blood and CSF readily yield C. neoformans using standard techniques. 3. Filamentous Fungi Many filamentous fungi are ubiquitous in the environment. Although easily grown from sputum, proof of infection, except in very immunosuppressed pa-
Candida and Other Fungi 461 tients, almost always requires biopsy evidence of tissue invasion. When suspicion of invasive aspergillosis or zygomycosis arises, the resident should be immedi- ately transferred to an acute care facility so that appropriate histopathological and microbiological tests can be performed. IV. THERAPEUTIC INTERVENTIONS A. Localized Mucocutaneous Infections 1. Skin Infections Both dermatophyte and yeast infections of the skin usually respond to topical ther- apy with creams or lotions (52). Lotions or sprays are easier to apply to large or hairy areas. Particularly for tinea cruris and intertrigenous candidiasis, the af- fected area should be kept as dry as possible; otherwise, recurrence is likely after discontinuation of the antifungal agent. Scalp infections often require systemic treatment with an antifungal agent. However, tinea versicolor rarely requires ther- apy with a systemic agent and often responds to the application of selenium sul- fide shampoo (10). For residents who have extensive skin lesions, oral azole agents or terbinafine can be used to clear the lesions more quickly. Terbinafine or itraconazole are generally used for dermatophyte infections, and itraconazole or fluconazole for Candida infections. Terbinafine has fewer drug-drug interactions than itraconazole and, for that reason, should be used first for those older adults who require systemic therapy for dermatophyte infections. 2. Nail Infections Onychomycosis does not respond to topical therapy (31,53–55) (Table 4). Either itraconazole or terbinafine, both of which accumulate in the nail plate, can be used to treat onychomycosis. Toenail infection is more difficult to cure than fingernail infection. Treatment with oral itraconazole or terbinafine, given as pulsed therapy Table 4 Recommended Management of Onychomycosis Keep nails short and straight to avoid ingrown toenails File nails that have become hypertrophic Wash feet daily and dry well, especially between the toes, after bathing Keep feet dry with use of antifungal powder and cotton socks Avoid sharing instruments for nail clipping and filing among patients Make a diagnosis of fungal infection by looking at nail clippings for fungal elements and, if the diagnosis is questionable, by culture of nail clippings, before treatment Treat with oral itraconazole or terbinafine for 3–6 months
462 Kauffman and Hedderwick 1 week out of each month for 3 to 6 months, or daily itraconazole or terbinafine for 3 months gives a higher success rate than previously seen with griseofulvin or ketoconazole (53–55). Terbinafine is less active against Candida than itracona- zole and is a second-line agent for Candida onychomycosis. 3. Oropharyngeal Candidiasis Oropharyngeal candidiasis is usually easily treated with clotrimazole troches or nystatin suspension. However, unless the underlying cause is removed, the infec- tion often returns after treatment is discontinued. Oral fluconazole or itraconazole suspension should be reserved for residents with more severe disease, such as might occur after chemotherapy or radiation therapy. Treatment of denture stom- atitis requires removal of the dentures at night and vigorous brushing and disin- fection of the appliance, along with topical antifungal solutions or lozenges. For recalcitrant cases, systemic therapy with oral fluconazole, in addition to local measures related to the appliance, are usually effective. Treatment options have recently been extensively reviewed (32). 4. Vulvovaginitis The successful treatment of Candida vaginitis is usually accomplished by the ap- plication of topical creams or suppositories (37,38). Older women who are frail or suffering from dementia may find topical agents difficult to apply. Single-dose fluconazole is an attractive, easily tolerated alternative for these residents and is preferred by many women. Removing any precipitating factors is important to prevent recurrence. However, some women will continue to have recurrent infec- tion; treatment with suppressive doses of fluconazole or ketoconazole is helpful in this circumstance (38). B. Candiduria The treatment of candiduria is debated (39,40,50,51,56). Given the benign nature of candiduria and our inability to differentiate colonization from infection, anti- fungal therapy should not be given unless the resident appears to have symp- tomatic urinary tract infection or obstruction of the collecting system due to Can- dida (Table 3). Candiduria will often disappear with removal of the predisposing factors (22,57). Thus, the first step is to remove the indwelling urinary catheter and stop antibiotics, if possible. When treatment is deemed necessary, flucona- zole, 400 mg for the first dose then 200 mg daily for 2 weeks, has been shown to be effective (51,57). However, lower doses have been used in some studies (58,59). Bladder irrigation with amphotericin B can be used to eliminate can- diduria, but it is unclear whether this reflects treatment of lower tract infection or merely eradication of colonization (50,58,59).
Candida and Other Fungi 463 C. Systemic Infections The management of residents suspected of an invasive fungal infection will al- most always involve transfer of the resident to an acute care facility for diagnosis and initial treatment. 1. Candidiasis Residents who develop invasive candidiasis while in the LTCF will almost always be transferred to an acute care hospital. Alternatively, residents with established Candida infection of certain sites, such as osteoarticular structures and eye, often are transferred from an acute care hospital to a LTCF after their condition has sta- bilized, for the purpose of receiving parenteral antifungal therapy. In this situa- tion, it is recommended that consultation with an infectious diseases consultant be obtained. Candidemia and invasive candidiasis can be treated with either ampho- tericin B or fluconazole (51). For severely ill residents, those with infection caused by C. glabrata or C. krusei, and those with certain end-organ disease, am- photericin B remains the drug of choice. 2. Cryptococcosis Cryptococcal meningitis requires induction treatment with intravenous ampho- tericin B and oral flucytosine. Combination therapy should continue for at least 2 weeks or until the CSF cultures become negative and the resident has begun to im- prove (60). Consolidation therapy with oral fluconazole is given for 10 weeks or longer, depending on the resident’s response, and may be carried out in the LTCF. Pulmonary cryptococcosis without evidence of disseminated infection can be treated with fluconazole in most cases; the drug should be continued until all le- sions have resolved (24). 3. Invasive Filamentous Fungi Chronic necrotizing pulmonary and sino-orbital aspergillosis are usually treated initially with amphotericin B (61). Patients are almost always in hospital during the initiation of antifungal therapy, but may continue with long-term antifungal treatment in the LTCF with either amphotericin B or itraconazole. Patients with zygomycoses are treated with amphotericin B given in high doses, because Rhizopus and Mucor species are only modestly susceptible to this drug and resistant to other antifungal agents. Surgical debridement of all necrotic tissue is essential. D. Specific Antifungal Agents 1. Azoles Azole agents have become the preferred treatment for localized yeast infections when topical agents have not proved effective, and they play an important role in
464 Kauffman and Hedderwick the treatment of systemic infections (62–64). Three azole antifungal agents are currently available: ketoconazole, itraconazole, and fluconazole. Itraconazole has largely supplanted ketoconazole for treatment of localized infections, and it also has an adjunctive role in the treatment of some forms of aspergillosis. Fluconazole has a narrower spectrum of activity than itraconazole, but remains the primary azole used for the treatment of cryptococcosis and all forms of candidiasis. Fluconazole has superior pharmacological attributes, in that the oral formu- lation is almost 100% bioavailable, the drug distributes into most compartments including the eye and the CSF, and it is excreted as active drug in the urine. Itra- conazole and ketoconazole, however, have problematic absorption, are lipophilic and accumulate in the skin and nails, and are metabolized by the liver and not ex- creted as active drug into the urine. Ketoconazole and itraconazole require gastric acid for absorption (63,64). In addition, the capsule formulation of itraconazole is absorbed best when given with food. Therefore, histamine receptor antagonists (H2 blockers), antacids, and proton pump inhibitors should not be administered to patients requiring therapy with ketoconazole or itraconazole (Table 5). In older adults who are more likely to have achlorhydria than younger adults, absorption of both of these agents may be erratic (65,66). The oral suspension of itraconazole, given on an empty stom- ach, has approximately 30% better absorption than the capsule formulation. Whether this is also true for older adults has not been established. This formula- tion should always be used in those patients who must also take agents that inhibit gastric acid secretion. Azoles have few side effects. Rash and nausea can occur with all azoles. Fluconazole causes reversible alopecia. Hepatitis, which can occur with all azoles, is rare, but can be life-threatening. Liver function tests should be mea- sured at baseline and after several weeks of therapy. Mild elevations of serum alanine aminotransferase or aspartate aminotransferase (twofold to threefold in- crease over normal) do not require stopping the drug, but do require careful fol- low-up. If the levels increase further, the drug should be discontinued. Itracona- zole causes hypertension, edema, and hypokalemia; although uncommon, this Table 5 Drugs That Decrease Serum Azole Levels Azole Drugs that decrease azole levels Ketoconazole Rifampin, isoniazid, phenytoin and all drugs that decrease gastric acid* Itraconazole capsules Rifampin, rifabutin, phenytoin, carbamazepine and all Itraconazole suspension drugs that decrease gastric acid* Fluconazole Rifampin, rifabutin, phenytoin, carbamazepine Rifampin * Includes antacids, histamine receptor antagonists (H2) blockers, proton pump inhibitors.
Candida and Other Fungi 465 Table 6 Effects of Azole Antifungal Drugs on Serum Levels of Other Drugs Drug affected Ketoconazole Itraconazole Fluconazole Cyclosporine Increased* Increased* Increased* Tacrolimus Increased* Increased* Increased* Warfarin Increased* Increased* Increased* Phenytoin Increased* None known Increased* Carbamazepine None known None known Increased* Terfenadine Increased† Increased† No effect Astemizole Increased† Increased† None known Cisapride Increased† Increased† Increased† Digoxin None known Increased* None known Oral hypoglycemics Increased* None known Increased* Isoniazid Decreased None known None known Rifampin Decreased None known None known Rifabutin None known None known Increased Triazolam, Increased Increased Increased alprazolam, None known Increased† None known midazolam Lovastatin, simvastatin, etc. * Significant interaction, monitor serum levels of drug and/or clinical status. † Life-threatening interaction; avoid the combination. complication occurs most often in older adults and often requires stopping the drug (66). The azoles have the potential to produce serious and even life-threatening drug-drug interactions through their actions on the cytochrome P450 system (62–64) (Table 6). Itraconazole and ketoconazole are the most problematic. Pa- tients receiving cholesterol-lowering agents, such as simvastatin and lovastatin, can develop life-threatening rhabdomyolysis when given itraconazole. Increased serum levels of warfarin, phenytoin, and oral hypoglycemic agents occur when azoles are given with these commonly used drugs in older adults. Itraconazole in- creases serum levels of digoxin in some, but not all patients. Coadministration of an azole with cisapride, astemizole, or terfenadine is contraindicated because the azoles potentiate the electrocardiogram (QT) prolongation induced by these drugs. Thus, in older adults who take many medications and may have multiple healthcare providers, careful attention to existing drug regimens before adding an azole is important to avoid serious and life-threatening drug-drug interactions. 2. Terbinafine Oral terbinafine is readily absorbed and concentrates in the stratum corneum, hair follicles, and nails. The drug is usually tolerated well, although loss of or changes in
466 Kauffman and Hedderwick taste perception can occur and are distressing to patients. Hepatitis, Stevens-John- son syndrome, and neutropenia are serious but rare side effects. Terbinafine is me- tabolized by P450 enzymes in the liver, but it does not affect the metabolism of other drugs, such as warfarin, as is noted with the azoles (67). However, rifampin will in- crease the metabolism of terbinafine, thus decreasing serum terbinafine levels. 3. Amphotericin B Amphotericin B is the drug of choice for several serious fungal infections. This drug will rarely be initiated in the LTCF. However, patients are increasingly trans- ferred to a LTCF to be given amphotericin B after the initial phase of the infection has been treated in hospital. Nephrotoxicity manifested by a rising creatinine, hypokalemia, or hypo- magnesemia, is seen in almost all older adults receiving amphotericin B (65,66,68). Patients with underlying renal disease show a more rapid rise in creatinine. Con- comitant use of other nephrotoxic drugs should be avoided. During amphotericin B treatment, salt restriction should be stopped and diuretics should be used very ju- diciously, because enhanced nephrotoxicity, presumably related to sodium deple- tion and hypovolemia, is likely to occur. Sodium loading can decrease nephrotox- icity, but this can be problematic in older adults who have pre-existing heart failure. Potassium and magnesium losses can be large and can contribute to other organ dysfunction; for this reason, electrolytes should be monitored carefully and replaced as soon as the serum levels show even a slight decrease. In many patients, intravenous repletion is ultimately required to keep pace with the renal loss. Infusion-related reactions are often experienced by patients receiving am- photericin B. Chills or rigors, fever, nausea, headache, and myalgias occur in the majority of patients treated. Many of these side effects can be diminished or elim- inated by administering certain drugs before the infusion (69). Three lipid formulations of amphotericin B are currently available: liposo- mal amphotericin B (L-AmB; AmBisome®), amphotericin B lipid complex (ABLC; Abelcet®), and amphotericin B colloidal dispersion (ABCD; Am- photec® or Amphocil®). Each differs from the others and from standard ampho- tericin B in respect to composition, pharmacological parameters, recommended dosages, toxicities, and cost, but all are less nephrotoxic. These agents have been reviewed recently (70,71). Because most older patients who require more than a few days of therapy with amphotericin B will develop some degree of renal fail- ure, the use of one of the less nephrotoxic lipid formulations is attractive. V. INFECTION CONTROL MEASURES A. Dermatophyte Infections With the exception of tinea capitis, transmission of dermatophytes from person to person is uncommon. Isolation of residents with these infections is unnecessary
Candida and Other Fungi 467 and not recommended. Rarely, transmission of tinea corporis from resident to res- ident or resident to healthcare worker by direct contact has occurred in LTCFs (5–8). It is important to quickly evaluate suspicious lesions to prevent transmis- sion that can occur before treatment is begun. In at least one outbreak, spread to healthcare workers was likely facilitated by a delay in treatment (5). Tinea capitis can also be spread by fomites, such as hats or hairbrushes. Transmission can occur from areas of skin and scalp that do not appear infected; thus, sharing of hairbrushes should not be allowed at any time. Dogs and cats, in- creasingly common in LTCFs, have been documented as a source for dermato- phyte infections, especially those caused by Microsporum canis (9). Most animals brought into LTCFs for pet therapy should be checked to be sure they are healthy. In the rare circumstance that a dog or cat is involved in an outbreak, the animal must be treated, as well as the residents, to eliminate the infection. Tinea pedis may be spread in public bathing facilities, such as pools and showers (72). Dermatophytes can remain viable on wet floors until they subse- quently adhere to feet (73). Private tubs and showers help obviate spread within a facility. If these are not available, simple measures, such as drying the feet well af- ter washing, will decrease dermatophyte adherence and the potential for infection (74). Additionally, disinfecting the tub or shower after each patient use with an ap- propriate agent, such as a quaternary product, will decrease spread among patients. B. Yeast Infections There is no evidence of intrafacility spread of tinea versicolor, and thus no need for isolation precautions for patients with this infection. Candida infections are primarily acquired from the person’s own endoge- nous flora. Transmission from person to person is distinctly unusual, although it has been documented in the acute care hospital setting (75,76). Scrupulous care of intravenous catheters, especially indwelling dialysis catheters and those used for total parenteral nutrition, using standard infection control techniques, is important to help prevent catheter-associated candidemia. Isolation precautions are not re- quired for patients with Candida infections. Cryptococcosis is acquired outside the facility and is not spread from per- son to person. Hands of healthcare workers are not a means of transmission of this organism. No isolation precautions are required for patients with cryptococcal in- fection. C. Invasive Filamentous Fungal Infections These infections are rarely acquired in the LTCF and are not transmitted from per- son to person or by healthcare workers. There is no need for isolation precautions for residents with aspergillosis or zygomycosis in LTCFs.
468 Kauffman and Hedderwick VI. PREVENTION A. Dermatophyte Infections Prevention of dermatophyte infections involves good local hygiene for residents of LTCFs. Skin should be kept dry and maceration avoided, if at all possible. Rou- tine visits by a podiatrist will lead to improved care of toenails and early diagno- sis and appropriate therapy for tinea pedia and onychomycosis. The feet should be washed and dried between the toes every day; heavy socks and shoes that increase sweating should be avoided and socks should be changed daily (29). Appropriate disinfection of communal showers will help decrease the risk for spread of tinea pedis. The sharing of hairbrushes, hats, and scarves should be avoided to help pre- vent tinea capitis. The use of standard precautions by healthcare workers will help to decrease the occurrence of outbreaks of tinea corporis (6,8). Prophylactic use of antifungal agents has no role to play in preventing dermatophyte infections. B. Yeast Infections Cutaneous yeast infections, such as intertrigo, onychomycosis, and paronychia, can be prevented by the measures described for dermatophytes. Prevention of oropharyngeal candidiasis is related directly to decreasing those factors that con- tribute to growth of Candida in the mouth. Avoiding drugs that cause xerostomia, decreasing the use of inappropriate broad-spectrum antibiotics, and emphasizing good dental hygiene will help to decrease the risk of thrush (32,34). The care of dentures is exceedingly important in the prevention of denture stomatitis. Den- tures should always be removed at night and should be cleaned daily by brushing with a denture brush and soaking in a disinfectant solution, such as chlorhexidine, or a commercially available denture cleanser (32). Prevention of Candida vulvovaginitis and urinary tract infections should fo- cus on removal of those factors that lead to infection. In the case of vulvovagini- tis, hyperglycemia, corticosteroid use, and broad-spectrum antibiotic therapy of- ten contribute to development of vaginitis and should be modified when feasible. Candida urinary tract infections rarely occur in the absence of indwelling urethral catheters and broad-spectrum antibiotic use. One option that can be used more readily in men than women in LTCFs is the use of intermittent rather than long- term catheterization; however, it has not been proved that this will decrease the risk for Candida urinary tract infections. Because most cases of candidemia and invasive candidiasis in the LTCF will likely occur in residents undergoing long-term hemodialysis or those with central intravenous catheters in place for nutritional supplementation or other rea- sons, prevention rests with scrupulous care of the catheter. Prophylactic use of azole agents to prevent Candida infections should be reserved for those patients who have frequent recurrent episodes of thrush or vulvovaginitis and for whom risk factors cannot be modified.
Candida and Other Fungi 469 C. Invasive Filamentous Fungal Infections Because infections with Aspergillus or the zygomycetes are rare in the LTCF and are not related to any specific practices in that setting, special preventive measures need not be taken. REFERENCES 1. Kauffman CA. Endemic mycoses in older adults. Infect Dis Clin Pract 1995; 4:41–45. 2. Kauffman CA. Fungal infections in older adults. Clin Infect Dis 2001; 33:550–555. 3. Roberts DT. Prevalence of dermatophyte onychomycosis in the United Kingdom: Re- sults of an omnibus survey. Br J Dermatol 1992; 126(suppl 39):23–27. 4. Heikkila H, Stubb S. The prevalence of onychomycosis in Finland. Br J Dermatol 1995; 133:699–703. 5. Peachey RDG, English MP. An outbreak of Trichophyton rubrum infection in a geri- atric hospital. Br J Dermatol 1974; 91:389–397. 6. Lewis SM, Lewis BG. Nosocomial transmission of Trichophyton tonsurans tinea cor- poris in a rehabilitation hospital. Infect Control Hosp Epidemiol 1997; 18:322–325. 7. Kane J, Leavitt E, Summerbell RC, Krajden S, Kasatiya SS. An outbreak of Tri- chophyton tonsurans dermatophytosis in a chronic care institution for the elderly. Eur J Epidemiol 1988; 4:144–149. 8. Shah PC, Krajden S, Kane J, Summerbell RC. Tinea corporis caused by Microspo- rum canis: Report of a nosocomial outbreak. Eur J Epidemiol 1988; 4:33–38. 9. Weitzman I, Summerbell RC. The dermatophytes. Clin Microbiol Rev 1995; 8:240– 259. 10. Borelli D, Jacobs PH, Nall L. Tinea versicolor: Epidemiologic, clinical, and thera- peutic aspects. J Am Acad Dermatol 1991; 25:300–305. 11. Fridkin SK, Jarvis WR. Epidemiology of nosocomial fungal infections. Clin Micro- biol Rev 1996; 9:499–511. 12. Hedderwick SA, Wan JY, Bradley SF, Sangeorzan JA, Terpenning MS, Kauffman CA. Risk factors for colonization with yeast species in a Veterans Affairs LTCF. J Am Geriatr Soc 1998; 46:849–853. 13. Jackson MM, Fierer J, Barrett-Connor E, Fraser D, Klauber MR, Hatch R, Burkhart B, Jones M. Intensive surveillance for infections in a LTCF. Am J Epidemiol 1992; 135:685–696. 14. Wilkieson C, Samaranayake LP, MacFarlane TW, Lamey PJ, Mackenzie D. Oral can- didiosis in the elderly in long term hospital care. J Oral Pathol Med 1991; 20:13–16. 15. Magaziner J, Tenney JH, DeForge B, Heber R, Muncie HL, Warren JW. Prevalence and characteristics of nursing home-acquired infections in the aged. J Am Geriatr Soc 1991; 39:1071–1078. 16. Komshian SV, Uwaydah AKJ, Sobel JD, Crane LR. Fungemia caused by Candida species and Torulopsis glabrata in the hospitalized patient: Frequency, characteris- tics and evaluation of factors influencing outcome. Rev Infect Dis 1989; 11:379–390. 17. Malani PN, Bradley SF, Little, RS, Kauffman CA. Trends in species causing fungemia in a tertiary care medical center over 12 years. Mycoses 2001; 44:446–449.
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Appendix A Definitions of Common Infections in Long-Term Care Facilities REFERENCE McGeer A, Campbell B, Emori TG, Hierholzer WJ, Jackson MM, Nicolle LE, Peppler C, Rivera A, Schollenberger DG, Simor, AE, Smith PW, Wang EE-L. Definitions of infection for surveillance in long-term care facilities. Am J Infect Control 1991; 19:1–7. I. CONDITIONS APPLICABLE TO DEFINITIONS A. Only new symptoms or acute changes in chronic symptoms that sug- gest possibility of an infection should be considered. B. Potential noninfectious causes of the symptoms and signs exhibited by the resident should always be considered before diagnosing an infec- tion. C. Infection should be diagnosed based on several supporting data and not on a single finding. Microbiological and radiological findings should be used only to confirm clinical evidence of infection. II. RESPIRATORY TRACT INFECTION A. Influenza-like illness 1. Temperature of 100.4°F (38°C) or higher AND 2. Presence of at least three of the following clinical manifestations: a. Chills b. New headache or eye pain c. Malaise or anorexia d. Sore throat 473
474 Appendix A e. Myalgia f. New or increased dry cough 3. Symptoms or signs must be present during influenza season (e.g., November to April in United States and Canada) to make the di- agnosis of influenza. B. Bronchitis or tracheobronchitis 1. Presence of at least three of the following clinical manifestations: a. New or increased cough b. New or increased sputum production c. Temperature of 100.4°F (38°C) or higher d. Pleuritic chest pain e. New or increased rales, rhonchi, wheezes, or bronchial breath- ing on physical examination of the chest. f. Indication of a change in status or breathing difficulty: - New or increased dyspnea OR - Respiratory rate higher than 25/minute OR - Worsening mental function OR - Worsening functional status C. Pneumonia 1. Presence of BOTH of the following criteria: a. Chest radiograph showing pneumonia, probable pneumonia or presence of a new infiltrate AND b. Presence of at least two of the clinical manifestations de- scribed for bronchitis and tracheobronchitis. III. URINARY TRACT INFECTION A. Noncatheter symptomatic urinary tract infection 1. Presence of at least three of the following clinical manifestations in the absence of an indwelling urinary catheter: - Temperature of 100.4°F (38°C) or higher or chills - New or increased dysuria, frequency, or urgency - New flank or suprapubic pain or tenderness - Change in urine character (new blood, foul smell, increased sed- iment grossly or by urinalysis) - Worsening of mental or functional status B. Catheter-related symptomatic urinary tract infection 1. Chronic indwelling urinary catheters lead to bacteriuria in almost 100% of cases, and bacteriuria is generally asymptomatic and re- quires no evaluation or treatment.
Definitions of Common Infections 475 2. In the absence of other site(s) of infection, the presence of fever and mental/functional status change meets criteria of symptomatic urinary tract infection. IV. SKIN INFECTIONS A. Cellulitis and soft tissue and wound infection 1. Presence of one of the following criteria: a. Purulence present at the wound, skin, or soft tissue site OR b. Presence of four or more of the following clinical manifesta- tions: - Temperature of 100.4°F (38°C) or higher OR worsening of mental/functional status - New or increasing heat at affected site - New or increasing redness at affected site - New or increasing swelling at affected site - New or increasing tenderness at affected site - New or increasing serous drainage at affected site B. Herpes zoster 1. Presence of both a. Vesicular rash AND b. Physician diagnosis or laboratory confirmation C. Scabies 1. Presence of both a. Maculopapular or pruritic rash, or both AND b. Physician diagnosis or laboratory confirmation V. GASTROINTESTINAL TRACT INFECTION A. Gastroenteritis 1. Presence of one of the following must be present: a. Two or more loose or watery stools above what is normal for a resident within a 24-hour period OR b. Two or more episodes of vomiting in a 24-hour period OR c. Both a stool culture positive for an enteric pathogen (e.g., Salmonella, Shigella, Escherichia coli 0157:H7, Campy- lobacter) and at least one manifestation compatible with gas- trointestinal tract infection (nausea, vomiting, abdominal pain or tenderness, diarrhea).
476 Appendix A VI. COMMENTS Criteria for common upper respiratory tract infections (“cold,” pharyngitis), con- junctivitis, ear infection, and oral infections are not described because they are generally of mild consequences and not life-threatening. Criteria for primary bacteremia or sepsis are omitted because obtaining blood cultures in a long-term care facility has not been documented to be benefi- cial or cost effective (See Appendix B).
Appendix B Guide to Evaluating Fever and Infection in a Long-Term Care Setting REFERENCE Bentley DW, Bradley S, High K, Schoenbaum S, Taler G, Yoshikawa TT. Prac- tice guideline for evaluation of fever and infection in long-term care facilities. Clin Infect Dis 2000; 31:640–653. I. CLINICAL EVALUATION A. Nursing aide should measure temperature, blood pressure, heart rate, and respiratory rate. 1. Fever is defined as: a. One or more rectal temperatures of more than 100° F (37.8°C) OR b. Two or more oral temperatures of more than 99° F (37.2°C) OR c. Temperature increase of 2°F (1.1°C) over baseline regardless of technique of measurement B. An initial evaluation regarding possible sites of infection should be done by the onsite nurse, and the findings should be communicated to the responsible physician, advance-practice nurse, or physician assis- tant. C. Document the full extent of the evaluation in the medical record. If di- agnostic interventions are purposefully withheld, the reasons should be clearly stated in the record. 477
478 Appendix B II. LABORATORY TESTS The diagnostic tests recommended should only be implemented where there are no previous advance directives that limit aggressive medical interventions. A. Suspected infection: complete blood cell count 1. A complete blood count, including peripheral white blood cell (WBC) count and differential cell count on all residents suspected of harboring an infection. 2. Elevated WBC count is 14,000 WBCs/mm3 or greater 3. A “left shift” is more than 6% band neutrophils or metamyelocytes OR total band neutrophil count 1,500 cells/mm3 or greater. B. Urinary tract infection 1. Diagnostic tests for suspected urinary tract infection should be re- served for only those residents who fulfill criteria for symptomatic urinary tract infection (see Appendix A). Evaluation should not be performed for asymptomatic bacteriuria. 2. Appropriately collected urine specimens are the following: a. Men 1) Clean catch or midstream specimen, provided resident is functionally capable OR 2) Freshly applied clean condom external catheter b. Women 1) Midstream specimen after proper perineal cleansing if resident is functionally capable OR 2) In-and-out catheterization 3. Initial evaluation should be a urine examination for WBCs (pyuria) by leukocyte esterase dipstick and microscopic examination for WBCs. a. If no pyuria (Ͻ10 WBCs per high-power field of spun urine on light microscopy or negative leukocyte esterase test) is found, urine culture is not indicated. b. Presence of pyuria should be followed by performing a urine culture with antibiotic sensitivity tests. 4. If urosepsis is suspected, resident should be considered for transfer to an acute care facility with blood cultures, urine culture, and urine Gram stain on unspun urine performed at the acute care facility. C. Sepsis or bacteremia: Blood cultures Blood cultures are not recommended for residents of long-term care fa- cilities (LTCFs) with suspected bacteremia or sepsis. These residents warrant transfer to an acute care facility provided there is approval by resident, resident’s family, or person with medical durable power of at- torney.
Guide to Evaluating Fever and Infection 479 D. Pneumonia 1. Pulse oximetry should be performed on residents with a respiratory rate higher than 25 per minute to document hypoxemia (oxygen saturation of Ͻ90%) as a clue to the diagnosis of pneumonia. Test is also helpful in predicting mortality and impending respiratory failure. 2. Chest radiograph should be performed if hypoxemia is docu- mented or radiograph is suspected to identify the presence of a new infiltrate compatible with pneumonia. Test can also exclude other complicating conditions involving the lungs (e.g., abscess, effu- sion) 3. Respiratory secretions (expectorated sputum or nasopharyngeal aspirate) should be obtained to assess for presence of purulence. A purulent specimen should be Gram stained for organisms and cytological screening for squamous epithelial cells (to determine quality of specimen). If stain of sputum or aspirate demonstrates less than 25 squamous epithelial cells per low-power field by light microscopy, then specimen can be acceptable for culture and sensitivity studies. E. Respiratory viral infection Obtain swab samples from throat and nasopharynx from several resi- dents at onset of an outbreak of suspected respiratory viral infection. Place swabs in a single tube containing refrigerated viral transport media and transport them to an experienced laboratory for virus iso- lation and rapid diagnostic testing for influenza A and other common viruses. F. Skin and soft tissue infections 1. Cellulitis Cultures should be performed under select conditions. Surface swabs are not indicated. Fine-needle aspiration of skin lesion is in- dicated if there is evidence of an abscess, an unusual pathogen is suspected (e.g., gram-negative bacilli in diabetics), or initial an- tibiotic treatment has been unsuccessful. 2. Pressure ulcers If a pressure ulcer demonstrates purulence or poor healing, send the purulent drainage or tissue obtained at surgical debridement or biopsy for culture. Surface swabs from pressure ulcers are not clin- ically useful. 3. Scabies Scrape several typical scabies burrows and examine by light mi- croscopy for mites, eggs, or mite feces on mineral oil prepara- tions.
480 Appendix B G. Infectious diarrhea 1. Stool specimen for diarrhea evaluation is not indicated if the resi- dent has a low-grade fever, new-onset diarrhea, and no clinical de- terioration, and there is no outbreak of diarrhea in the LTCF. 2. If resident develops diarrhea and has received antibiotics within the previous 30 days, suspect Clostridium difficile etiology. Sub- mit a stool specimen for C. difficile toxin assay. If specimen is neg- ative for toxin and diarrhea persists, submit one or two additional stool specimens. 3. If resident has high fever, abdominal cramps, or bloody diarrhea, or demonstrates WBCs in the stool and there is no history of re- ceiving antibiotics within the previous 30 days, submit stool for culture for isolation of common invasive enteropathogens (e.g., Salmonella, Shigella, Campylobacter, Escherichia coli 0157:H7). However, many of these residents will require transfer to an acute care facility because of associated bacteremia, sepsis, or dehydra- tion. III. INDICATIONS FOR TRANSFER TO AN ACUTE CARE FACILITY A. Upon admission of a person to an LTCF, general parameters for con- sidering transfer to an acute care facility for a resident should be recorded in the chart. Advance directives should also be part of this statement. B. Decisions regarding transfer of an LTCF resident to an acute care fa- cility should ultimately be at the discretion of the attending physician consistent with an existing advanced directive or as informed by the resident, resident’s family, or designated person with medical durable power of attorney. C. In the absence of an advance directive or directions from the resident, resident’s family, or designated person with medical durable power of attorney, the attending physician’s decision regarding a transfer should be based on available institutional policies regarding transfer to an acute care facility. If such a policy is not available, then the following parameters should be reviewed when a transfer is considered: 1. Clinical condition, underlying disease(s), and prognosis of the res- ident 2. Efficacy and cost-effectiveness of interventions and acute care 3. Capacity of the LTCF to provide necessary care and support to the resident
Index Acquired immunity, 38–39 [Aging] age-related changes in, 39–40 dietary supplements, 43–45 innate immunity, interaction between, herpes zoster infection, changes in 40–42 immunity, 37 immune dysfunction, 33–50 Acquired immunodeficiency syndrome, immune response, 38–42 ethical issues in, 88 immunity, 34 immunosenescence, 34 Acute care facility vs. long-term care influenza, chronic illness, 35–36 facility, 15–26 innate immunity, 38–39 acquired immunity, interaction initial evaluation, 18–20 between, 40–42 recognition of infection, 17–18 medications staffing, 15–17 immune potentiating effects, 43–46 subacute care infection control, 20–21 with immunopotentiation, 45–46 transfer, to acute care setting, 21–22, 408 nursing home population, 7 Administration of facility, alliance with, in nutritional deficiencies, 43 modification of immunity with, 43 infection control program, 125 physiological changes associated with, Admission criteria, to subacute units, 9 162–163 Admissions, social worker, partnerships pneumonia, chronic illness, 36–37 between, 127 AIDS (see Acquired immunodeficiency Advance directives, 85–86 syndrome) health care proxy, 86 Airborne precautions, 104–106 preferences for treatment, 85–86 education, 105–106 Aging (see also Geriatric healthcare) resident placement, 105 acquired immunity, age-related changes in, 39–40 bacteria, resistant, 37–38 chronic illness, in elderly, 35–38 481
482 Index [Airborne precautions] [Antibiotic resistance] resident transport, 105 minimum inhibitory, bactericidal respiratory protection, 105 concentrations, 366 novel drugs, future developments, 377 Amantadine, 201–202 penicillin-resistant pneumococci, 369 dosing, 201–202 pharmacological principles, 366–367 efficacy, 201 quinolones, 374–375 resistance, 202 mechanism of action, 374–375 side effects, 202 mechanism of resistance, 375 resistant pathogens, emergence of, 364 Aminoglycosides, 164–165 tetracyclines, 373–374 resistance, 375–376 trimethoprim-sulfamethoxazole, 372–373 mechanism of action, 376 mechanism of action, 372 mechanism of resistance, 376 mechanism of resistance, 373 Amphotericin B, 466 Antifungal agents, 168, 463–466 Anorexia Antimicrobial therapy, 155–171 drugs causing, geriatric population, 66 adverse drug events, 160–161 in geriatric population, drugs causing, 66 aging, physiological changes associated Antibiotic era, 27 Antibiotic regimens with, 162–163 in infection control program, 124–125 aminoglycosides, 164–165 pneumonia, 231 antifungal agents, 168 pressure ulcers, infected, 273 antituberculous agents, 168 Antibiotic resistance, 363–382 antiviral agents, 168–169 aminoglycosides, 375–376 assessment of, 156 beta-lactams, 165 mechanism, 376 clindamycin, 165–166 beta-lactams, 367–369 for common infections, 160 ceftazidime-resistant gram-negative drug factors, 161–164 empirical antimicrobial therapy, 157–159 bacilli, 367–368 epidemiologic investigation, 149 glycopeptides, 376–377 fluoroquinolones, 166–167 glycylcyclines, 374 geriatric population, 30–31 gram-negative bacteria, prevalence of, inappropriate use of, 161 initiation of, criteria for, 157, 158–159 433–435 macrolides, 165 impact of, 365 methicillin-resistant Staphylococcus infection control program, 124 ketolides, 371–372 aureus, 396 macrolides, 369–372 optimizing use of, 156–161 pharmacodynamics, 163–164 mechanism of action, 370 pharmacokinetics, 162–163 mechanism of resistance, 370–371 methicillin-resistant Staphylococcus absorption, 162 clearance, 163 aureus, 369 distribution, 162–163 microbiological principles, 366 metabolism, 163 microorganisms, 108–111 pneumonia, 229–232 pressure ulcers, 272 colonized, 109 resistant organisms, 146–147, 363–472 culture status of resident, 109 infected, 109 resident with, room placement, 110 uncontained, 109 minimum bactericidal concentration, 366
Index 483 [Antimicrobial therapy] Candida, 451–452, 454–457, 460, 463 tissue penetration, 163 Capacity, decisional, ethical issues, trimethoprim-sulfamethoxazole, 167 urinary tract infection, 185–187 84–88 utilization review, 159–160 Case-control studies, in epidemiologic Antituberculous agents, 168 investigation, 141 Antiviral agents, 168–169 Case definition, line listing, in respiratory viruses, 202 epidemiologic investigation, APIC (see Association for Professionals 138–139 Catheters in Infection Control and chronic indwelling, urinary tract Epidemiology) infection, 179, 188 Appetite stimulants, 64–65 long-term indwelling Artifact, surveillance, in epidemiologic infection control, 189 investigation, 136–137 urinary tract infection, 181, 184, Aspergillosis 190–191 pulmonary, chronic necrotizing, CDC (see Center for Disease Control 457–458 and Prevention) sino-orbital, 457 Ceftazidime-resistant gram-negative Association for Professionals in Infection bacilli, 367–368 Control and Epidemiology, 128 Cellulitis, 290–295 Atypical presentations of infection, 72–73 clinical manifestations, 291–292 Azoles, 463–465 diagnosis, 292–293 epidemiology, 290–291 Bacteria, resistant, 37–38 infection control, 293–294 Bactericidal concentrations, 366 prevention, 294–295 Bacteriuria therapy, 293 Center for Disease Control and Prevention, distribution of infecting organisms, 177 website, 129 symptomatic, 184–185 Chemoprophylaxis, respiratory viruses, Baseline temperature, 75 201–204 Beneficence, 80–81 Children, visits to elderly parent, 4 Beta-lactams, 165 Chronic illness, 33–50 AmpC, inducible chromosomal, in elderly, 35–38 immunosenescence, 34 431–432 Chronic indwelling catheter, urinary tract Bush–Jacoby–Medeiros classification, 430 infection, 179, 188 extended-spectrum, 431 Chronic necrotizing pulmonary metallo, 432 aspergillosis, 457–458 resistance, 367–369 Clearance, antimicrobial therapy, 163 Body mass index, nutritional assessment Clindamycin, 165–166 Cohort studies, in epidemiologic and, 57 investigation, 141 Bronchitis, 235–237 Commercial formula supplements, 58–62 trials of, 59 clinical manifestations, 236 Communication, infection, in healthcare diagnosis, 236 facility, 101–102 epidemiology, 235–236 Community services, availability of, 6 infection control, 237 therapy, 236–237 Bush–Jacoby–Medeiros classification, beta-lactamases, 430
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