An algorithm to estimate the importance of bacterial acquisition routes in hospital settings.

An algorithm is presented to calculate likelihoods of acquisition routes using only individual patient data concerning period of stay and microbiologic surveillance (without genotyping). The algorithm also produces estimates for the prevalence and the number of acquisitions by each route. The algorithm is applied to colonization data of third-generation cephalosporin-resistant Enterobacteriaceae (CRE) from September 2001 to May 2002 in two intensive care units (ICUs) (n = 277 and n = 180, respectively) of Utrecht, Kingdom of the Netherlands. Genotyping and epidemiologic linkage are used as the reference standard. Surveillance cultures were obtained on admission and twice weekly thereafter. All CREs were genotyped. According to the reference standard, the daily prevalence of CRE in ICU-1 and ICU-2 was 26.1% (standard deviation: 15.4) and 15.1% (standard deviation: 13.4), respectively, with five of 23 (21.7%) and six of 21 (28.6%) cases of acquired colonization being of exogenous origin, respectively. On the basis of the algorithm, the endogenous route was responsible for more acquisitions than the exogenous route (p = 0.003 and p < 0.001 for ICU-1 and ICU-2, respectively). The estimated number of acquisitions is 30 and 27, and the estimated prevalence is 27.6% and 17.6% for ICU-1 and ICU-2, respectively. By use of longitudinal colonization data only, the algorithm determines the relative importance of acquisition routes taking patient dependency into account.

Potential confounding in evaluating infection-control interventions in hospital settings: changing antibiotic prescription.

The colonization dynamics of antibiotic-resistant pathogens in hospital settings are complex, with multiple and continuously interacting variables (e.g., introduction of resistance, infection-control practices, antibiotic use). Quantification of these variables is indispensable in the evaluation of intervention studies, because these variables represent potential confounders. In this article, the complexity of colonization dynamics is described. Through a systematic review, we identified studies that evaluated the modification of antibiotic prescription to reduce antibiotic resistance in intensive care units (n=19), and the extent of confounding-control was determined. Most studies evaluated antimicrobial restriction/substitution (n=12) or antibiotic rotation (n=4). Sixteen studies had a prospective cohort design (before-after), of which 12 were without a control group. Introduction of antibiotic resistance was determined in 10 studies. The relative importance of colonization routes and adherence to infection-control measures were not determined in any study. Therefore, it remains uncertain whether observed changes in the prevalence of antibiotic resistance after intervention were causally related to the intervention. Appropriate choices of study design, primary end point (colonization rates rather than infection rates) and statistical tests, determination of colonization routes, and control of potential confounders are needed to increase validity of intervention studies.

Unnoticed spread of integron-carrying Enterobacteriaceae in intensive care units.

BACKGROUND: Integrons are strongly associated with multidrug resistance in Enterobacteriaceae. Little is known about the natural history of integron-associated resistance in hospitals during nonoutbreak periods. The prevalence of integrons and the incidence of cross-transmission and horizontal gene transfer in Enterobacteriaceae with reduced susceptibility to cephalosporins (ERSC) were determined for 2 intensive care units (ICUs). METHODS: Microbiological surveillance using rectal swab samples obtained 2 times per week and genotyping using amplified fragment-length polymorphism (AFLP) were used to determine colonization with and genetic relatedness of ERSC. IntI1 integrase polymerase chain reaction (PCR), conserved-segment PCR, restriction fragment-length polymorphism, and DNA sequencing were used to determine the prevalence and contents of integrons. RESULTS: Of 457 patients, 121 patients were colonized with ERSC, and 174 isolates underwent AFLP and PCR. In 34 isolates obtained from 31 patients, 11 different integrons were identified; these integrons encoded resistance to streptomycin/spectinomycin, gentamicin/tobramycin/kanamycin, chloramphenicol, and trimethoprim. Integrons could be divided into 7 clusters of > or =2 isolates each. Compared with isolates that were negative for integrons, isolates that were positive for integrons were associated with resistance to piperacillin, cephalosporins, aminoglycosides, and quinolones. Acquisition rates of integron-carrying ERSC were 10 cases per 1000 patient-days in the first ICU and 8 cases per 1000 patient-days in the second ICU, with most cases (26 of 34) being acquired during the ICU stay. Nineteen episodes resulted from cross-transmission. In addition, 2 cases of interspecies transfer and 1 case of intraspecies transfer of integrons were recorded. Younger age was independently associated with acquisition of integron-carrying ERSC (hazard ratio, 0.953; 95% confidence interval, 0.926-0.987). CONCLUSION: Surveillance, genotyping, and integron analysis identified previously unnoticed outbreaks of integron-carrying ERSC. Cross-transmission appeared to be the dominant route of transmission. Therefore, barrier precautions are necessary to prevent further spread.

Are active microbiological surveillance and subsequent isolation needed to prevent the spread of methicillin-resistant Staphylococcus aureus?

BACKGROUND: Infection-control strategies usually combine several interventions. The relative value of individual interventions, however, is rarely determined. We assessed the effect of daily microbiological surveillance alone (e.g., without report of culture results or isolating colonized patients) as an infection-control measure on the spread of methicillin-susceptible Staphylococcus aureus (MSSA) and methicillin-resistant S. aureus (MRSA) in a medical intensive care unit (MICU). METHODS: Colonization of patients with MSSA and MRSA was assessed by cultures of nasal swabs obtained daily and, if a patient was intubated, by cultures of additional endotracheal aspirates. Pulsed-field gel electrophoresis was used to determine relatedness between MSSA or MRSA isolates in surveillance cultures (i.e., cultures of nasal swab specimens obtained daily) and those in clinical cultures (i.e., any other culture performed for clinical purposes). Adherence to infection-control measures by health care workers (HCWs) was determined by observations of HCW-patient interaction. RESULTS: During a 10-week period, surveillance cultures were performed for 158 patients. Fifty-five patients (34.8%) were colonized with MSSA, and 9 (5.7%) were colonized with MRSA. Sixty-two patients were colonized before admission to the hospital (53 had MSSA, and 9 had MRSA). Two patients appeared to have acquired MSSA in the MICU, but, on the basis of genotyping analysis, we determined that this was not the result of cross-acquisition. CONCLUSION: Surveillance cultures and genotyping of MRSA and MSSA isolates demonstrated the absence of cross-transmission among patients in the MICU, despite ongoing introduction of these pathogens. Reporting culture results and isolating colonized patients, as suggested by some guidelines, would have falsely suggested the success of such infection-control policies.

Beta-lactam susceptibilities and prevalence of ESBL-producing isolates among more than 5000 European Enterobacteriaceae isolates.

In vitro susceptibility to 15 beta-lactam antibiotics was evaluated using Enterobacteriaceae isolated during the SENTRY Antimicrobial Surveillance Program. Piperacillin/tazobactam was the most active penicillin against Escherichia coli, Proteus mirabilis, Klebsiella oxytoca and Klebsiella pneumoniae (94.9%, 98.3%, 87.4% and 82.9% of isolates susceptible). Of the cephalosporins, cefepime was most effective against Escherichia coli, Proteus mirabilis and Enterobacter cloacae (99.2%, 96.3% and 95.2% of isolates susceptible, respectively) and cefoxitin against Klebsiella oxytoca and Klebsiella pneumoniae (98.6% and 95.6% of isolates susceptible). Carbapenems had excellent activity (> or =99.5% of all isolates). ESBL-production was confirmed with the ESBL-Etest and disk diffusion test in 1.3% of Escherichia coli isolates, 18.4% of Klebsiella pneumoniae, 12.6% of Klebsiella oxytoca and 5.3% of Proteus mirabilis isolates.