Walter E. Stamm

Nosocomial Acquisition of Clostridium difficile Infection

We studied the acquisition and transmission of Clostridium difficile infection prospectively on a general medical ward by serially culturing rectal-swab specimens from 428 patients admitted over an 11-month period. Immunoblot typing was used to differentiate individual strains of C. difficile. Seven percent of the patients (29) had positive cultures at admission. Eighty-three (21 percent) of the 399 patients with negative cultures acquired C. difficile during their hospitalizations. Of these patients, 52 (63 percent) remained asymptomatic and 31 (37 percent) had diarrhea; none had colitis. Patient-to-patient transmission of C. difficile was evidenced by time-space clustering of incident cases with identical immunoblot types and by significantly more frequent and earlier acquisition of C. difficile among patients exposed to roommates with positive cultures. Of the hospital personnel caring for patients with positive cultures, 59 percent (20) had positive cultures for C. difficile from their hands. The hospital rooms occupied by symptomatic patients (49 percent) as well as those occupied by asymptomatic patients (29 percent) were frequently contaminated. Eighty-two percent of the infected cohort still had positive cultures at hospital discharge, and such patients were significantly more likely to be discharged to a long-term care facility. We conclude that nosocomial C. difficile infection, which was associated with diarrhea in about one third of cases, is frequently transmitted among hospitalized patients and that the organism is often present on the hands of hospital personnel caring for such patients. Effective preventive measures are needed to reduce nosocomial acquisition of C. difficile.

Guidelines for Antimicrobial Treatment of Uncomplicated Acute Bacterial Cystitis and Acute Pyelonephritis in Women

This is part of the series of practice guidelines commissioned by the Infectious Diseases Society of America (IDSA) through its Practice Guidelines Committee. The purpose of this guideline is to provide assistance to clinicians in the diagnosis and treatment of two specific types of urinary tract infections (UTIs): uncomplicated, acute, symptomatic bacterial cystitis and acute pyelonephritis in women. The guideline does not contain recommendations for asymptomatic bacteriuria, complicated UTIs, Foley catheter-associated infections, UTIs in men or children, or prostatitis. The targeted providers are internists and family practitioners. The targeted groups are immunocompetent women. Criteria are specified for determining whether the inpatient or outpatient setting is appropriate for treatment. Differences from other guidelines written on this topic include use of laboratory criteria for diagnosis and approach to antimicrobial therapy. Panel members represented experts in adult infectious diseases and urology. The guidelines are evidence-based. A standard ranking system is used for the strength of the recommendation and the quality of the evidence cited in the literature reviewed. The document has been subjected to external review by peer reviewers as well as by the Practice Guidelines Committee and was approved by the IDSA Council, the sponsor and supporter of the guideline. The American Urologic Association and the European Society of Clinical Microbiology and Infectious Diseases have endorsed it. An executive summary and tables highlight the major recommendations. Performance measures are described to aid in monitoring compliance with the guideline. The guideline will be listed on the IDSA home page at http://www.idsociety.org It will be evaluated for updating in 2 years.

A Controlled Trial of Intravaginal Estriol in Postmenopausal Women with Recurrent Urinary Tract Infections

BACKGROUND Recurrent urinary tract infections are a problem for many postmenopausal women. Estrogen replacement restores atrophic mucosa, lowers vaginal pH, and may prevent urinary tract infections. METHODS We enrolled 93 postmenopausal women with a history of recurrent urinary tract infections in a randomized, double-blind, placebo-controlled trial of a topically applied intravaginal estriol cream. Midstream urine cultures were obtained at enrollment, monthly for eight months, and whenever urinary symptoms occurred. Vaginal cultures and pH measurements were obtained at entry and after one and eight months. The women were assigned to receive either estriol (n = 50) or placebo (n = 43), both administered intravaginally; 36 and 24, respectively, completed the eight months of follow-up. RESULTS The incidence of urinary tract infection in the group given estriol was significantly reduced as compared with that in the group given placebo (0.5 vs. 5.9 episodes per patient-year, P < 0.001). Survival analysis showed that more of the women in the estriol group than in the placebo group remained free of urinary tract infection (P < 0.001). Lactobacilli were absent in all vaginal cultures before treatment and reappeared after one month in 22 of 36 estriol-treated women (61 percent) but in none of the 24 placebo recipients (P < 0.001). With estriol the mean vaginal pH declined from 5.5 to 3.8 (P < 0.001), whereas there was no significant change with placebo. The rate of vaginal colonization with Enterobacteriaceae fell from 67 percent to 31 percent in estriol recipients but was virtually unchanged (from 67 to 63 percent) in the placebo recipients (P < 0.005). Side effects were minor, but caused 10 estriol recipients (28 percent) and 4 placebo recipients (17 percent) to discontinue treatment. CONCLUSIONS The intravaginal administration of estriol prevents recurrent urinary tract infection in postmenopausal women, probably by modifying the vaginal flora.

DIAGNOSIS AND TREATMENT OF UNCOMPLICATED URINARY TRACT INFECTION

Acute uncomplicated urinary tract infection is one of the most common problems for which young women seek medical attention and accounts for considerable morbidity and health care costs. Acute cystitis or pyelonephritis in the adult patient should be considered uncomplicated if the patient is not pregnant or elderly, if there has been no recent instrumentation or antimicrobial treatment, and if there are no known functional or anatomic abnormalities of the genitourinary tract. Most of these infections are caused by E. coli, which are susceptible to many oral antimicrobials, although resistance is increasing to some of the commonly used agents. Review of the published data suggests that a 3-day regimen is more effective than a single-dose regimen for all antimicrobials tested. Regimens with trimethoprim-sulfamethoxazole seem to be more effective than those with beta lactams, regardless of the duration. Because of increasing resistance to trimethoprim-sulfamethoxazole, an alternative regimen such as nitrofurantoin (in a 7-day regimen), a fluoroquinolone, or an oral third-generation cephalosporin may be a better empiric choice in some areas. Acute pyelonephritis caused by highly virulent uropathogens in an otherwise healthy woman may be considered an uncomplicated infection. The optimal treatment duration for acute uncomplicated pyelonephritis has not been established, but 10- to 14-day regimens are recommended. We prefer to use antimicrobials that attain high renal tissue levels, such as a fluoroquinolone, trimethoprim-sulfamethoxazole, or an aminoglycoside, for pyelonephritis. Acute uncomplicated cystitis or pyelonephritis in healthy adult men is uncommon but is generally caused by the same spectrum of uropathogens with the same antimicrobial susceptibility profile as that seen in women.

Diagnosis of coliform infection in acutely dysuric women

We reevaluated conventional criteria for diagnosing coliform infection of the lower urinary tract in symptomatic women by obtaining cultures of the urethra, vagina, midstream urine, and bladder urine. The traditional diagnostic criterion, greater than or equal to 10(5) bacteria per milliliter of midstream urine, identified only 51 per cent of women whose bladder urine contained coliformis. We found the best diagnostic criterion to be greater than or equal to 10(2) bacteria per milliliter (sensitivity, 0.95; specificity, 0.85). Although isolation of less than 10(5) coliforms per milliliter of midstream urine has had a low predictive value of previous studies of asymptomatic women, the predictive value of the criterion of greater than or equal to 10(2) per milliliter was high (0.88) among symptomatic women the prevalence of coliform infection exceeded 50 per cent. In view of these findings, clinicians and microbiologists should alter their approach to the diagnosis and treatment of women with acute symptomatic coliform infection of the lower urinary tract.

Increasing antimicrobial resistance and the management of uncomplicated community-acquired urinary tract infections.

Uncomplicated community-acquired urinary tract infections (UTIs) are among the most common infections in women, accounting for more than 8 million office visits per year in the United States as well as significant morbidity and health care costs (1). Current management of these infections is usually empirical, without the use of a urine culture or susceptibility testing to guide therapy. The rationale for this approach is based on the narrow and predictable spectrum of etiologic agents that cause acute cystitis and their susceptibility patterns (2). However, as with many community-acquired infections, antimicrobial resistance among the pathogens that cause community-acquired UTIs is increasing (3-6). As the problem of antimicrobial resistance becomes more widespread, the use of narrow-spectrum, inexpensive antimicrobial agents becomes less feasible, affecting both the cost of and access to health care for patients. In addition, such infections as uncomplicated community-acquired UTI, which have traditionally been readily treatable, are now becoming therapeutic challenges. Perhaps the most significant change in resistance among uropathogens has been the increase in the prevalence of resistance to trimethoprimsulfamethoxazole (TMPSMX), the current drug of choice in the United States for empirical therapy for uncomplicated UTI in women. In addition, TMPSMX resistance has been associated with concurrent resistance to other antibiotics, resulting in multidrug-resistant uropathogens (7, 8). However, although several reports have focused on changing patterns of in vitro resistance of uropathogens to TMPSMX, the clinical significance of this resistance has not been well studied. Therefore, implications for health care providers are not yet clear. This review highlights the problem of antimicrobial resistance in acute uncomplicated community-acquired UTI, focusing on TMPSMX resistance, and summarizes the few available data regarding clinical outcomes associated with in vitro resistance. Finally, we outline recommendations for empirical treatment of uncomplicated UTI in a period of evolving antimicrobial resistance. Etiologic Agents in Uncomplicated Community-Acquired UTIs Although susceptibility patterns have changed, the spectrum of agents causing community-acquired UTI has remained relatively constant. Escherichia coli accounts for 75% to 90% of cases; Staphylococcus saprophyticus accounts for 5% to 15% (particularly in younger women); and enterococci and nonE. coli aerobic gram-negative rods, such as Klebsiella species and Proteus mirabilis, account for the remaining 5% to 10% (2, 9). Although less well studied, the spectrum of agents causing uncomplicated pyelonephritis is similar to that causing acute cystitis (10, 11). Pharmacologic Issues The antimicrobial agents used to treat uncomplicated community-acquired UTIs include the -lactams, TMPSMX, nitrofurantoin, fosfomycin, and the fluoroquinolones. All of these agents achieve high urinary concentrations, usually greatly exceeding the expected serum levels (Table 1). Of note, susceptibility breakpoints from the National Committee for Clinical Laboratory Standards are based on serum rather than urine concentrations of these antimicrobial agents, except for nitrofurantoin and fosfomycin, which are exclusively used for treatment of cystitis (12). Table 1. Pharmacokinetic Characteristics of Selected Antimicrobial Agents Used To Treat Community-Acquired Urinary Tract Infections The aminopenicillins, ampicillin and amoxicillin, and most cephalosporins are rapidly excreted into the urine and attain high urinary concentrations (Table 1) (12-15). The peak serum and urinary concentrations of amoxicillin are higher than those achieved with a similar dose of ampicillin (12). In the 1970s, ampicillin was commonly used for treatment of acute cystitis. However, because of increasing in vitro resistance, as well as lower efficacy and more adverse effects than are seen with other available UTI antimicrobial agents, the -lactams in general are no longer recommended for empirical UTI therapy (1). In certain settings, such as during pregnancy or when enterococci are suspected, ampicillin or amoxicillin may still be an appropriate choice for acute UTI (1). The combination of TMP and SMX has been shown to be synergistic against a variety of organisms, including such aerobic gram-negative rods as E. coli (16). This combination has been used for treatment of UTI for more than two decades, although the commonly used 3-day regimen has not been formally approved by the U.S. Food and Drug Administration. After a single oral dose of one double-strength tablet (TMP, 160 mg; SMX, 800 mg), the peak urine concentrations are approximately 35 and 3 to 4 times higher, respectively, than serum levels (Table 1). Trimethoprim also concentrates in prostatic tissue at levels 2 to 3 times higher than those found in serum (12). Nitrofurantoin is one of the oldest urinary antiinfective agents in use. The macrocrystalline formulation requires frequent dosing (every 6 hours); however, a modified monohydratemacrocrystal form delays gastric uptake and allows twice-daily dosing. Nitrofurantoin is used primarily for treatment of cystitis because it does not attain appreciable serum levels (Table 1). It is 90% renally excreted, and therefore the urine concentration is very high, making it an effective urinary anti-infective agent for most gram-positive and gram-negative uropathogens (17). Fosfomycin tromethamine is a phosphonic acid derivative that is newly licensed for treating uncomplicated cystitis caused by E. coli or Enterococcus faecalis (18). It is not approved for use for cystitis caused by S. saprophyticus or for treatment of pyelonephritis. It achieves very high concentrations in the urine and persists in the urine for more than 24 hours (Table 1). The fluoroquinolones each have individual pharmacodynamic properties (12, 19, 20). The first fluoroquinolones widely used for treatment of UTI, namely norfloxacin, ciprofloxacin, ofloxacin, and levofloxacin, all have excellent bioavailability and achieve high urinary concentrations (Table 1). Their penetration into prostatic and renal tissue is also excellent. Some of the newer fluoroquinolones, such as sparfloxacin and trovafloxacin, are not excreted in high urinary concentrations and thus should not be used for treatment of uncomplicated pyelonephritis or complicated UTI. The fluoroquinolones also have a significant postantibiotic effect against gram-negative organisms (12). In Vitro Susceptibility Data Many recent studies have reported the resistance profiles of uropathogens to antimicrobial agents commonly used to treat UTI (3-8). Much of this in vitro data comes from laboratory-based surveys that often do not define the sex, age, clinical syndrome, or location (inpatient vs. outpatient) of the patients from whom the urine specimens are collected. Therefore, the reported rates of resistance may vary depending on whether the study sample consists primarily of outpatients with uncomplicated UTIs or patients with complicated nosocomial UTIs. The data presented here focus on studies that clearly define the study sample as women with uncomplicated community-acquired UTI. Although susceptibility profiles vary by each specific organism and antimicrobial combination, some general trends have clearly emerged. Resistance of E. coli and other uropathogens to -lactams, such as ampicillin, and the first-generation cephalosporins has continued to increase in the past decade and now approaches 40% in most studies (3, 6). Most gram-negative uropathogens are still susceptible to the combination of amoxicillinclavulanate, but the expense and gastrointestinal side effects of this drug make it a less desirable choice for empirical treatment of uncomplicated UTI (2). Moreover, it has been suggested that the failure rate with this drug is high when the uropathogen is resistant to ampicillin but susceptible to amoxicillinclavulanate (22). Nitrofurantoin and the fluoroquinolones have retained in vitro activity against most E. coli isolates that cause uncomplicated community-acquired UTI (>99% in most studies) (Table 2). However, nitrofurantoin is less active against nonE. coli gram-negative rods (3, 6) and inactive against Proteus and Pseudomonas species. The fluoroquinolones have had consistently high activity against essentially all gram-negative uropathogens seen in women with uncomplicated community-acquired UTI but are active against only 60% to 70% of enterococci, depending on the study (3, 6). Both nitrofurantoin and the fluoroquinolones retain good in vitro activity against S. saprophyticus (6), although increased failure rates have been reported with the use of single doses of fluoroquinolones to treat S. saprophyticusrelated UTIs (1). Table 2. in Vitro Susceptibility of Escherichia coli from U.S. Studies of Urinary Tract Infection As mentioned, the most substantial change in resistance prevalence has been to TMPSMX. Resistance to TMPSMX among uropathogens in the community was relatively infrequent in the United States in the early 1990s (Table 2). At that time, McCarty and colleagues (9) conducted a multicenter trial of low-dose ciprofloxacin compared with standard-dose ofloxacin and TMPSMX for treatment of acute uncomplicated cystitis in women. They reported only a 7% prevalence of TMPSMX resistance among the E. coli isolates. The rates of resistance did not increase to levels that might compromise clinical effectiveness until the mid-1990s (Table 2). We conducted a cross-sectional survey of urine isolates from a well-defined sample of outpatient women in western Washington State who had acute uncomplicated cystitis. We found that the prevalence of TMPSMX resistance among E. coli was 9% in 1992 but had increased to 18% by 1996, the last year of the study (3). Of interest, in a California student health sample, Dyer and coworkers found that the prevalence of UTI isolate

A prospective study of risk factors for symptomatic urinary tract infection in young women.

BACKGROUND Although acute urinary tract infections are common in young women, the associated risk factors have not been defined prospectively. METHODS We recruited sexually active young women who were starting a new method of contraception at a university health center or a health maintenance organization (HMO) and monitored them for six months for symptomatic urinary tract infections. Daily diaries and serial interviews were used to collect data on potential risk factors. RESULTS Among 796 women, the incidence of urinary tract infections per person-year was 0.7 in the university cohort (mean age, 23 years; n = 348) and 0.5 in the HMO cohort (mean age, 29; n = 448). In both cohorts, there were strong dose-response relations between the risk of infection and both recent use of a diaphragm with spermicide (respective relative risks for one, three, and five days of use in the past week, 1.42, 2.83, and 5.68 in the university cohort, P<0.001; and 1.29, 2.14, and 3.54 in the HMO cohort, P=0.04) and recent sexual intercourse (respective relative risks for one, three, and five days with intercourse in the past week, 1.37, 2.56, and 4.81 in the university cohort, P<0.001; and 1.24, 1.91, and 2.96 in the HMO cohort, P=0.002). The risk of acute infection was also associated with a history of recurrent infection (relative risk, 5.58 in the university group and 2.10 in the HMO group) but not with cervical-cap use, ABO-blood-group nonsecretor phenotype, or delayed postcoital voiding. CONCLUSIONS Among sexually active young women the incidence of symptomatic urinary tract infection is high, and the risk is strongly and independently associated with recent sexual intercourse, recent use of a diaphragm with spermicide, and a history of recurrent urinary tract infections.

Transmission of Infection by Gastrointestinal Endoscopy and Bronchoscopy

Spurred in part by the acquired immunodeficiency syndrome (AIDS) epidemic, both health care workers and the lay public have become keenly interested in preventing the iatrogenic transmission of infections. Recently, reports of the transmission of infections via contaminated endoscopes have generated concern. We review the reported evidence of infections transmitted by flexible gastrointestinal and pulmonary endoscopes, the circumstances surrounding transmission of these infections, and recommended means to prevent such transmission. Methods We identified all relevant English-language articles published between 1966 and July 1992 through prominent review articles and a MEDLINE search (keywords: endoscopy, bronchoscopy, infections, transmission, and disinfection). We also manually searched bibliographies of identified articles to find additional sources. The entire search yielded 265 articles, all of which were reviewed in depth. General Considerations Flexible endoscopy is a common clinical procedure; an estimated 8.7 million gastrointestinal and 580 000 pulmonary flexible endoscopies were done in the United States in 1989 [1]. The risk for transmitting infections via these procedures depends on three factors: exposure of the endoscope to microorganisms, cleaning and disinfection procedures, and instrument design. Depending on the origin of the contaminating microorganisms, transmission of infection can be categorized as either patient-to-patient or environment-to-patient (Figure 1). During a procedure, an endoscope can be contaminated with whatever organisms are contained in patient secretions. Environmental contamination typically results from flushing or cleaning the endoscope with contaminated solutions. Whether contamination of the endoscope persists depends on the quantity and nature of the microorganisms. Some microbes are inherently more resistant to disinfectants (Figure 2), the efficacy of which depends on type, concentration, and duration of exposure. If patient material, such as blood, feces, or secretions, remains on or in the endoscope after cleaning, the effectiveness of subsequent disinfection diminishes. Figure 1. Nosocomial transmission of microorganisms via endoscopes. Figure 2. Resistance of microorganisms to disinfectants. Because endoscopes are made of fragile, heat-sensitive materials, they are routinely decontaminated by high-level disinfection, not sterilization [2]. Gastrointestinal endoscopes, with their multiple internal channels and valves (Figure 3), are more complex than the single-channeled bronchoscopes. In general, the more complex the instrument, the more crevices, joints, or surface pores there are and, hence, the more problematic cleaning and disinfection becomes [2]. Figure 3. Cross-section of typical gastrointestinal endoscope. Transmission of Specific Microorganisms Salmonella Infections Salmonella infections occur frequently in the United States; for example, more than 41 000 culture-positive patients were reported to the Centers for Disease Control (CDC) in 1989[3]. A chronic asymptomatic carrier state, defined by the continued fecal excretion of Salmonella organisms for more than 1 year, develops in approximately 3% of persons after S. typhi infection (typhoid fever) [4] and in fewer than 1% of persons after nontyphoidal Salmonella infection [5]. Both acutely infected persons and chronic carriers are thus potential sources of endoscopic contamination. Many disinfectants, including glutaraldehyde, phenolics, and iodophors, effectively kill salmonellae [2]. Transmission of Salmonella infections by endoscopy has occurred with many serotypes, including S. agona, S. kedougou, S. newport, S. oranienburg, S. oslo, S. typhi, and S. typhimurium [6-14]. Of the 84 patients reported to have developed such infections, 6 patients developed septicemia and 1 patient died. In most cases, the disinfectant (hexachlorophene, cetrimide, chlorhexidine, or quaternary ammonium compounds) used to clean the endoscopes had relatively little microbiocidal activity against salmonellae. In one outbreak, investigators identified inadequately disinfected colonic biopsy forceps as the source of infection [9]. Pseudomonas Infections Pseudomonas aeruginosa flourishes in warm, damp environments. Typical environmental reservoirs include respiratory equipment, sinks, and water bottles [15]. Most acute P. aeruginosa infections, which often involve the lungs, are nosocomially acquired. Among healthy adults, P. aeruginosa can colonize many body sites, as evidenced by isolation from throat (0% to 7%), sputum (2%), and stool (3% to 24%). Hospitalized patients, as well as patients with certain chronic lung diseases, have higher colonization rates [16]. Potential sources of endoscope contamination with Pseudomonas species thus include environmental reservoirs, acutely infected patients, and colonized patients. Like Salmonella species, P. aeruginosa is susceptible to glutaraldehyde, phenolics, and iodophors [2]. Most P. aeruginosa infections transmitted by endoscopy occurred after endoscopic retrograde cholangiopancreatography and resulted from environment-to-patient transfer of organisms. In all cases, the investigators isolated P. aeruginosa from some part of the endoscope. These infections resulted in bacteremia in 45 patients, of whom 4 died [17-26]. Most infections were caused by the use of an inadequate disinfectant [21, 22], contamination of an inner channel [18, 20], or incomplete drying of the endoscope channels before overnight storage [23, 26]. One epidemic, however, occurred despite the use of glutaraldehyde after each procedure and ceased only after replacement of the endoscope [19]. The first reports of bronchoscopic transmission of P. aeruginosa involved patients who developed Pseudomonas pneumonia [27, 28]. In a subsequent report, investigators cultured P. aeruginosa from the bronchoscopic washings of 11 patients; 1 patient, who was immunosuppressed, developed severe pneumonia [29]. The investigators isolated P. aeruginosa from the aspiration-irrigation channel of the bronchoscope, and the outbreak continued until they sterilized the bronchoscope with ethylene oxide. Mycobacteria Approximately 22 000 new cases of active tuberculosis occur in the United States each year [30], and an estimated 10 to 15 million persons carry Mycobacterium tuberculosis in its dormant phase [31]. After many years of decline, the incidence of tuberculosis in the United States began increasing dramatically in 1986 [30], predominantly because of an increasing number of cases in HIV-infected patients [32]. Infections with mycobacteria commonly found in the environment, such as M. avium-intracellulare complex, M. chelonae, and M. fortuitum, have also recently increased [33]. Unfortunately, studies determining the sensitivity of mycobacteria to various disinfectants are conflicting. In general, cetrimide, chlorhexidine, and iodophors are considered unreliable. Glutaraldehyde is widely accepted as a mycobactericidal agent, but the time required for disinfection remains undefined [34-36]. In the first reports of the bronchoscopic transmission of M. tuberculosis, the investigators, who disinfected the bronchoscopes with iodophor, advocated using a more effective disinfectant such as glutaraldehyde [37, 38]. In three subsequent cases, the patients developed clinically apparent M. tuberculosis infection despite rigorous cleaning and disinfection of the bronchoscope; the suction valve, with its spring-operated sleeve, seemed the most likely source of contamination [39]. The investigators tested this hypothesis by contaminating bronchoscopes with M. fortuitum; after they routinely cleaned and disinfected the instrument, M. fortuitum remained in all valves. Among other mycobacteria, M. chelonae has most commonly been associated with endoscopic transmission. In a large outbreak, M. chelonae was isolated from bronchial washings, brushings, or sputum in 72 patients [40]. Two patients developed clinical disease and one patient died. After recognizing the outbreak, the investigators changed from glutaraldehyde disinfection of the bronchoscopes to ethylene oxide sterilization. Nevertheless, they continued to isolate M. chelonae from clinical specimens until they discovered punctured suction channels in two of the bronchoscopes; M. chelonae was isolated from slimy material in the interior of both instruments. Hepatitis B Virus On average, more than 300 000 cases of primary hepatitis B virus (HBV) occur each year in the United States [41], and approximately 5% to 10% of patients develop persistent HBV infection. The estimated number of chronic HBV carriers in the United States ranges from 750 000 to 1 000 000 [42]. In infected persons, hepatitis B surface antigen (HBsAg) has been found in various body fluids, including serum, feces, bile, and saliva [43]. The inability to culture HBV has limited the evaluations of its environmental stability and its susceptibility to disinfectants. Alternative approaches include measuring the presence of HBsAg or inoculating chimpanzees. A study in chimpanzees showed that HBV-contaminated inanimate objects, if not properly cleaned and disinfected, can harbor and transmit the virus for up to 1 week [44]. Most of the commonly used disinfectant and sterilization procedures, however, inactivate HBV [45, 46]. Two studies have shown the potential for the endoscopic transmission of HBV. In one study, iodophor-isopropyl alcohol removed HBsAg from surfaces of endoscopes used in four HBsAg-positive patients, but not from the cytology brushes or biopsy forceps [47]. In the other study, an endoscope and a biopsy forceps were immersed for 15 minutes in gastric juice containing 1.0% serum and Iodine-125-HBsAg, and, despite subsequent disinfection with chlorhexidine and cetrimide for 15 to 20 minutes, they were both positive for Iodine-125-HBsAg [48]. One group of investigators documented the endoscopic transmission of HB

Catheter-associated urinary tract infections : epidemiology, pathogenesis, and prevention

Catheter-associated urinary tract infections (UTIc) remain the most common nosocomial infection. Although usually benign, UTIc cause bacteremia in 2-4% of patients and have been associated with a case fatality rate three times as high as nonbacteriuric patients. Risk factors for UTIc identified in multivariate analyses include increasing duration of use, female sex, absence of systemic antibiotics, and disconnection of the catheter-collecting tube junction. Recent studies suggest that most episodes of low colony count bacteriuria (10(2)-10(4) cfu/ml) rapidly progress to high (greater than or equal to 10(5)/ml) colony counts within 24-48 hours. In persons with long-term catheterization, bacteriuria inevitably develops and the infecting strains change frequently. In this setting, Proteus and Morganella species produce catheter encrustations and persistent bacteriuria. Routes of bacterial entry have been well defined and differ by gender, with the periurethral route predominating in women and the intraluminal route in men. Growth of bacteria in biofilms on the inner surface of catheters promotes encrustation and may protect bacteria from antimicrobial agents. Bacterial virulence factors have not been well characterized in UTIc, but fimbrial adhesins have been associated with bacterial persistence in the catheterized urinary tract, and urease production has been associated with stone formation and catheter encrustation. Recent efforts to prevent UTIc have focused mainly on preventing bacterial entry to the urinary tract or eradicating bacteriuria after its onset and have been largely unsuccessful. Systemic antimicrobials, sealed tubing and catheter junctions, silver ion-coated catheters, and antiseptics in the collecting bag have all been efficacious in one or more controlled trials. Failure to stratify patients by major risk factors, especially gender, antimicrobial exposure, and catheter duration, makes interpretation of many trials difficult. Further research in the areas of innovative catheter system design, bacterial-host epithelial cell interaction, and targeted antimicrobial prophylaxis seem the most likely approaches to controlling UTIc in the future.

Detection of Intracellular Bacterial Communities in Human Urinary Tract Infection

Background Urinary tract infections (UTIs) are one of the most common bacterial infections and are predominantly caused by uropathogenic Escherichia coli (UPEC). While UTIs are typically considered extracellular infections, it has been recently demonstrated that UPEC bind to, invade, and replicate within the murine bladder urothelium to form intracellular bacterial communities (IBCs). These IBCs dissociate and bacteria flux out of bladder facet cells, some with filamentous morphology, and ultimately establish quiescent intracellular reservoirs that can seed recurrent infection. This IBC pathogenic cycle has not yet been investigated in humans. In this study we sought to determine whether evidence of an IBC pathway could be found in urine specimens from women with acute UTI. Methods and Findings We collected midstream, clean-catch urine specimens from 80 young healthy women with acute uncomplicated cystitis and 20 asymptomatic women with a history of UTI. Investigators were blinded to culture results and clinical history. Samples were analyzed by light microscopy, immunofluorescence, and electron microscopy for evidence of exfoliated IBCs and filamentous bacteria. Evidence of IBCs was found in 14 of 80 (18%) urines from women with UTI. Filamentous bacteria were found in 33 of 80 (41%) urines from women with UTI. None of the 20 urines from the asymptomatic comparative group showed evidence of IBCs or filaments. Filamentous bacteria were present in all 14 of the urines with IBCs compared to 19 (29%) of 66 samples with no evidence of IBCs (p < 0.001). Of 65 urines from patients with E. coli infections, 14 (22%) had evidence of IBCs and 29 (45%) had filamentous bacteria, while none of the gram-positive infections had IBCs or filamentous bacteria. Conclusions The presence of exfoliated IBCs and filamentous bacteria in the urines of women with acute cystitis suggests that the IBC pathogenic pathway characterized in the murine model may occur in humans. The findings support the occurrence of an intracellular bacterial niche in some women with cystitis that may have important implications for UTI recurrence and treatment.