Erika M. C. D'Agata

High rate of false-negative results of the rectal swab culture method in detection of gastrointestinal colonization with vancomycin-resistant enterococci.

The diagnostic accuracy of the rectal swab (RS) culture method in identifying gastrointestinal colonization with vancomycin-resistant enterococci (VRE) is not known. Serial quantitative stool cultures, skin cultures, and RS cultures were performed for patients with VRE infections to assess the false-negative rate of the RS and the prevalence of skin colonization, a prerequisite for cross-transmission, at varying VRE stool densities. A total of 35 stool samples were obtained from 13 patients. The sensitivity of the RS culture was 58%; it ranged from 100%, at VRE densities of > or =7.5 log10 colony forming units (cfu) per gram of stool, to 0%, at densities of < or =4.5 log10 cfu per gram of stool. Skin colonization was detected at these low VRE stool densities, but it was more common at higher VRE densities (P<.001). Antibiotic exposure was significantly associated with higher VRE stool densities (P<.001). The high false-negative rate of the RS may be contributing to the continued increase in the prevalence of VRE.

Mupirocin Prophylaxis to Prevent Staphylococcus aureus Infection in Patients Undergoing Dialysis: A Meta-analysis

A systematic review of the English-language literature was performed to determine the overall benefit of mupirocin therapy in reducing the rate of Staphylococcus aureus infection among patients undergoing hemodialysis (HD) or peritoneal dialysis (PD). Included studies met the following criteria: they were randomized clinical trials or cohort studies; cohorts consisted of adults (age, > or =18 years) requiring HD or PD; mupirocin therapy was administered to the treatment group, and placebo or no therapy was administered to the control group; and the primary outcome of interest was the difference in the number of S. aureus infections among mupirocin-treated and -untreated patients. Ten studies described in 9 articles were analyzed. A total of 2445 patients were included in the analysis. Use of mupirocin reduced the rate of S. aureus infections by 68% (95% confidence interval [CI], 57%-76%) among all patients undergoing dialysis; risk reductions were 80% (95% CI, 65%-89%) among patients undergoing HD and 63% (95% CI, 50%-73%) among patients undergoing PD. When data were stratified by type of infection, S. aureus bacteremia was found to be reduced by 78% among patients undergoing HD, and peritonitis and exit-site infections were found to be reduced by 66% and 62%, respectively, among patients undergoing PD. Mupirocin prophylaxis substantially reduces the rate of S. aureus infection in the dialysis population. Optimal regimens that minimize the emergence of mupirocin resistance need to be explored.

Rapidly rising prevalence of nosocomial multidrug-resistant, Gram-negative bacilli: a 9-year surveillance study.

OBJECTIVE To examine and quantify the temporal trends of nosocomial multidrug-resistant, gram-negative bacilli. DESIGN A 9-year surveillance study was conducted. Multidrug resistance was defined as resistance to 3 or more antimicrobial classes. SETTING Tertiary-care institution. RESULTS From 1994 to 2002, multidrug-resistant, gram-negative bacilli increased from 1% to 16% for multidrug-resistant Pseudomonas aeruginosa, 4% to 13% for multidrug-resistant Enterobacter species, 0.5% to 17% for multidrug-resistant Klebsiella species, 0% to 9% for multidrug-resistant Proteus species, and 0.2% to 4% for multidrug-resistant Escherichia coli (P < or = .05). The most common pattern of multidrug resistance was co-resistance to quinolones, third-generation cephalosporins, and aminoglycosides. CONCLUSION The rapid rise of multidrug-resistant, gram-negative bacilli may warrant infection control programs to include these pathogens in strategies aimed at limiting the emergence and spread of antimicrobial-resistant pathogens.

An outbreak of Acinetobacter baumannii: the importance of cross-transmission.

OBJECTIVE To investigate an outbreak of nosocomial infections due to multidrug-resistant (MDR) Acinetobacter baumannii and to analyze the contribution of cross-transmission in the rise in infection rates. DESIGN Epidemiological investigation; molecular typing using pulsed-field gel electrophoresis (PFGE); matched case-control study to identify risk factors for infection. SETTING A 34-bed surgical intensive care unit at a tertiary-care hospital. PATIENTS Eighteen patients who developed MDRA baumannii nosocomial infection were matched to 36 patients who were admitted to the same surgical intensive care unit (SICU) room and did not develop an infection during the outbreak period. RESULTS Prior to the outbreak, the baseline attack rate of MDR A baumannii nosocomial infections was 3 per 100 patients per month. From February 1 through March 22, 1998, the attack rate rose to 16 per 100 patients per month, with a total of 18 infections. All isolates had indistinguishable PFGE patterns. Seventy environmental cultures were negative for MDR A baumannii. Following intense infection control education, the attack rate decreased to 4 per 100 patients per month. By conditional logistic regression, cases were exposed to a significantly higher number of patients with MDR A baumannii infections compared to controls (odds ratio, 1.1; 95% confidence interval, 1.01-1.2; P=.02), even after adjusting for length of SICU admission and exposure to antibiotics and invasive devices. CONCLUSION Cross-transmission between patients contributed to the rise in rates of MDRA baumannii infections. A common environmental source was not detected.

Multidrug-Resistant Gram-Negative Bacteria in a Long-Term Care Facility: Prevalence and Risk Factors

OBJECTIVES: To quantify the prevalence, risk factors, and mode of transmission associated with colonization by multidrug‐resistant gram‐negative bacteria (MDRGN) in the long‐term care (LTC) setting.

The Emerging Threat of Multidrug-Resistant Gram-Negative Organisms in Long-Term Care Facilities

Background Infections caused by antimicrobial-resistant bacteria are associated with substantial morbidity and mortality. Residents of long-term care facilities (LTCF) are among the main reservoirs of antimicrobial-resistant bacteria, including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE). Multidrug-resistant gram-negative organisms (MDRGN) are emerging as important pathogens among LTCF residents. Data on the clinical epidemiology of MDRGN, especially in comparison to VRE and MRSA, are limited. Methods All clinical cultures collected from residents of a 750-bed LTCF for a period of 2 years were analyzed for the presence of MDRGN, VRE, and MRSA. Multidrug resistance among gram-negative bacteria was defined as resistance to three or more antimicrobials or antimicrobial groups including extended-spectrum penicillins (ampicillin/sulbactam or piperacillin/tazobactam), cephalosporins (cefazolin or ceftriaxone), gentamicin, ciprofloxacin, and trimethoprim-sulfamethoxazole (TMP/SMX). Results A total of 1,661 clinical cultures were included in the analysis. MDRGN were recovered from 180 (10.8%) cultures, MRSA from 104 (6.3%), and VRE from 11 (0.6%). MDRGN were isolated more frequently than MRSA or VRE throughout the study period. The prevalence of MDRGN increased significantly from 7% in 2003 to 13% in 2005 (p = .001). More than 80% of MDRGN isolates were resistant to ciprofloxacin, TMP/SMX, and ampicillin/sulbactam. Resistance to three, four, and five or more antimicrobials were identified among 122 (67.8%), 47 (26.1%), and 11 (6.1%) MDRGN isolates, respectively. Conclusions Rates of MDRGN exceeded those of MRSA and VRE and increased throughout the study period. Resistance to multiple, commonly prescribed antimicrobials among MDRGN raises concerns about therapeutic options available to treat MDRGN infections among LTCF residents.

Vancomycin-Resistant Enterococci among Chronic Hemodialysis Patients: A Prospective Study of Acquisition

To determine the prevalence and rate of acquisition of vancomycin-resistant enterococci (VRE) among patients undergoing chronic (i.e., long-term) hemodialysis who were admitted to a tertiary care center, serial rectal cultures for VRE were performed at hospital admission and every 5 days until hospital discharge. A total of 7 (6%) of the 119 patients were colonized with VRE at admission. Six (19%) of the 32 patients who remained in the hospital > or =4 days acquired VRE. A nonambulatory status was significantly associated with colonization at admission (OR, 9.7; 95% CI, 1.8-53; P=.01), and vancomycin exposure was significantly associated with VRE acquisition (relative risk, 1.8; 95% CI, 1.1-2.9; P=.02). All patients acquired VRE from epidemiologically linked dialysis patients colonized with similar VRE genotypes. Hospital acquisition of VRE contributes substantially to the increasing prevalence of VRE in the chronic hemodialysis patient population.

Colonization with Multidrug-Resistant Gram-Negative Bacteria: Prolonged Duration and Frequent Cocolonization

BACKGROUND The characteristics of colonization with multidrug-resistant gram-negative bacteria (MDRGNB) in the gastrointestinal tract have not been well defined. Characterizing the duration of colonization, clearance of colonization, and frequency of cocolonization would provide important information for the development of interventions targeting the prevention of MDRGNB spread. METHODS From 31 October 2006 through 22 October 2007, serial rectal cultures were obtained every 3-4 weeks from residents of a long-term care facility. Clearance of colonization was defined as > or = 2 consecutive cultures from which MDRGNB were not recovered. Factors associated with clearance of colonization were analyzed using time-to-event methods. RESULTS Thirty-three patients colonized with 57 MDRGNB isolates were followed up for a median of 211 days (range, 63-356 days). Twenty (61%) of the patients were colonized with > or = 1 different MDRGNB species (median, 2 strains; range, 1-4 strains). The median duration of MDRGNB colonization was 144 days (range, 41-349 days). Clearance of colonization with all MDRGNB strains occurred in 3 patients (9%). Clearance of MDRGNB colonization, calculated by colonizing strain, occurred in 22 (39%) of 57 MDRGNB colonization episodes, with a rate of colonization clearance of 2.6 episodes per 1000 days. Clearance of multidrug-resistant Proteus mirabilis colonization occurred in 1 (6.7%) of 15 episodes, compared with clearance of 21 (50%) of 42 colonization episodes due to other MDRGNB species (hazard ratio, 0.1; 95% confidence interval, 0.01-0.78; P = .03). CONCLUSIONS Patient colonization with MDRGNB is prolonged, and a substantial proportion of patients are colonized with multiple MDRGNB species. Multidrug-resistant P. mirabilis may have a survival advantage in the gastrointestinal tract, compared with other MDRGNB species.

Colonization with broad-spectrum cephalosporin-resistant gram-negative bacilli in intensive care units during a nonoutbreak period: prevalence, risk factors, and rate of infection.

OBJECTIVE To define the epidemiology of broad-spectrum cephalosporin-resistant gram-negative bacilli in intensive care units (ICUs) during a nonoutbreak period, including the prevalence, the risk factors for colonization, the frequency of acquisition, and the rate of infection. DESIGN Prospective cohort study. SETTING Tertiary care hospital. PATIENTS Consecutive patients admitted to two surgical ICUs. MAIN OUTCOME MEASUREMENTS Serial patient surveillance cultures screened for ceftazidime (CAZ) resistance, antibiotic and hospital exposure, and infections. RESULTS Of the 333 patients enrolled, 60 (18%) were colonized with CAZ-resistant gram-negative bacilli (CAZ-RGN) at admission. Clinical cultures detected CAZ-RGN in only 5% (3/60) of these patients. By using logistic regression, CAZ-RGN colonization was associated with duration of exposure to cefazolin (odds ratio, 10.3; p < or = .006) and to broad-spectrum cephalosporins/penicillins (odds ratio, 2; p < or = .03), Acute Physiology and Chronic Health Evaluation III score (odds ratio, 1.2; p < or = .008), and previous hospitalization (odds ratio, 3.1; p < or = .006). Of the 100 patients who remained in the surgical ICU for > or = 3 days, 26% acquired a CAZ-RGN. Of the 14 infections caused by CAZ-RGN, 11 (79%) were attributable to the same species present in surveillance cultures at admission to the surgical ICU. CONCLUSIONS Colonization with CAZ-RGN was common and was usually not recognized by clinical cultures. Most patients colonized or infected with CAZ-RGN had positive surveillance cultures at the time of admission to the surgical ICU, suggesting that acquisition frequently occurred in other wards and institutions. Patients exposed to first-generation cephalosporins, as well as broad-spectrum cephalosporins/penicillins, were at high risk of colonization with CAZ-RGN. Empirical treatment of nosocomial gram-negative infections with broad-spectrum cephalosporins, especially in the critically ill patient, should be reconsidered.

The impact of different antibiotic regimens on the emergence of antimicrobial-resistant bacteria.

Backgroud The emergence and ongoing spread of antimicrobial-resistant bacteria is a major public health threat. Infections caused by antimicrobial-resistant bacteria are associated with substantially higher rates of morbidity and mortality compared to infections caused by antimicrobial-susceptible bacteria. The emergence and spread of these bacteria is complex and requires incorporating numerous interrelated factors which clinical studies cannot adequately address. Methods/Principal Findings A model is created which incorporates several key factors contributing to the emergence and spread of resistant bacteria including the effects of the immune system, acquisition of resistance genes and antimicrobial exposure. The model identifies key strategies which would limit the emergence of antimicrobial-resistant bacterial strains. Specifically, the simulations show that early initiation of antimicrobial therapy and combination therapy with two antibiotics prevents the emergence of resistant bacteria, whereas shorter courses of therapy and sequential administration of antibiotics promote the emergence of resistant strains. Conclusions/Significance The principal findings suggest that (i) shorter lengths of antibiotic therapy and early interruption of antibiotic therapy provide an advantage for the resistant strains, (ii) combination therapy with two antibiotics prevents the emergence of resistance strains in contrast to sequential antibiotic therapy, and (iii) early initiation of antibiotics is among the most important factors preventing the emergence of resistant strains. These findings provide new insights into strategies aimed at optimizing the administration of antimicrobials for the treatment of infections and the prevention of the emergence of antimicrobial resistance.