Rasmus Leistner

Nosocomial infection and antibiotic use: a second national prevalence study in Germany.

BACKGROUND In 2011, seventeen years after the first national study on the prevalence of nosocomial infections and antibiotic use in German hospitals, a second national prevalence study was carried out according to the specifications of the European Centre for Disease Prevention and Control (ECDC). METHODS The ECDC protocol, containing uniform surveillance definitions and ascertainment methods, was implemented. The only infections counted were those that were active or under treatment with antibiotics on the day of the study. In addition to the representative sample required by the ECDC, which consisted of 46 hospitals, further hospitals participated on a voluntary basis. RESULTS Data on 41 539 patients in 132 hospitals were analyzed. The prevalence of infections that had arisen during the current hospital stay was 3.8% in the overall group and 3.4% in the representative sample of 9626 patients in 46 hospitals. The prevalence of all nosocomial infections, including those acquired before the current hospital stay and still present upon admission, was 5.1% in both the overall group and the representative sample. The prevalence of antibiotic use on the day of the study was 25.5% and 23.3% in the two groups, respectively. CONCLUSION The prevalence of nosocomial infection has not changed since 1994, but the prevalence of antibiotic use has increased. In interpreting these findings, one should bear in mind that confounders may have influenced them in different directions: The mean length of hospital stay is now shorter than in 1994, but the mean age of hospitalized patients is higher.

Risk factors associated with the community-acquired colonization of extended-spectrum beta-lactamase (ESBL) positive Escherichia Coli. an exploratory case-control study.

Background The number of extended-spectrum beta-lactamase (ESBL) positive (+) Escherichia coli is increasing worldwide. In contrast with many other multidrug-resistant bacteria, it is suspected that they predominantly spread within the community. The objective of this study was to assess factors associated with community-acquired colonization of ESBL (+) E. coli. Methods We performed a matched case-control study at the Charité University Hospital Berlin between May 2011 and January 2012. Cases were defined as patients colonized with community-acquired ESBL (+) E. coli identified <72 h after hospital admission. Controls were patients that carried no ESBL-positive bacteria but an ESBL-negative E.coli identified <72 h after hospital admission. Two controls per case were chosen from potential controls according to admission date. Case and control patients completed a questionnaire assessing nutritional habits, travel habits, household situation and language most commonly spoken at home (mother tongue). An additional rectal swab was obtained together with the questionnaire to verify colonization status. Genotypes of ESBL (+) E. coli strains were determined by PCR and sequencing. Risk factors associated with ESBL (+) E. coli colonization were analyzed by a multivariable conditional logistic regression analysis. Results We analyzed 85 cases and 170 controls, respectively. In the multivariable analysis, speaking an Asian language most commonly at home (OR = 13.4, CI 95% 3.3–53.8; p<0.001) and frequently eating pork (≥3 meals per week) showed to be independently associated with ESBL colonization (OR = 3.5, CI 95% 1.8–6.6; p<0.001). The most common ESBL genotypes were CTX-M-1 with 44% (n = 37), CTX-M-15 with 28% (n = 24) and CTX-M-14 with 13% (n = 11). Conclusion An Asian mother tongue and frequently consuming certain types of meat like pork can be independently associated with the colonization of ESBL-positive bacteria. We found neither frequent consumption of poultry nor previous use of antibiotics to be associated with ESBL colonization.

The mother as most important risk factor for colonization of very low birth weight (VLBW) infants with extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-E)

OBJECTIVES This study aimed to determine the prevalence of and risk factors for colonization with extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-E) and methicillin-resistant Staphylococcus aureus (MRSA) in very low birth weight (VLBW; <1500 g) infants and their mothers. METHODS This investigation was conducted in the perinatal centre at the Charité Berlin between May 2012 and June 2013. VLBW infants and their mothers were screened for colonization with ESBL-E and MRSA. Demographic and clinical data were obtained from the German nationwide surveillance system for nosocomial infections in VLBW infants (NEO-KISS) and used to perform univariate and multivariate analyses. RESULTS Of 209 VLBW infants, 12 (5.7%) were colonized with ESBL-E. Eighteen of 209 (8.6%) ESBL-E-tested neonates were related to an ESBL-E-positive mother. Univariate analysis, strain typing and multivariate analysis (OR 7.4, 95% CI 2.1-26.7, P = 0.002) identified an ESBL-E-positive mother and maternal-neonatal transmission as a main source of colonization. The prevalence of MRSA was 2.3% (5 of 221) among VLBW infants. One of the 221 (0.5%) MRSA-tested neonates was related to an MRSA-positive mother. No risk factors for transmission of MRSA could be detected in this study. CONCLUSIONS Our study demonstrated that maternal-neonatal transmission of ESBL-E from mother to child is an important risk factor for colonization of VLBW infants. As a consequence, routine ESBL-E screening of neonates and mothers should be considered as a means of reducing neonatal morbidity and mortality.

Molecular characterisation of extended-spectrum β-lactamase (ESBL)-producing Escherichia coli isolates from hospital and ambulatory patients in Germany

The increase of Escherichia coli producing extended-spectrum β-lactamases (ESBL) in hospitals and their emergence as intestinal colonisers of healthy humans is of concern. Transmission ways and the extent of spread of distinct E. coli clones or ESBL genes among humans and animals via the food chain or the environment is a matter of debate. In this study we determined ESBL genotypes in E. coli isolates (n=233) resistant to 3rd generation cephalosporins from hospitals and medical practices using PCR and sequencing. Bacterial strain typing was performed by PCR-based phylogrouping, multilocus sequence typing (MLST) and a ST131-specific PCR. Results showed that CTX-M-15 (50.4%), CTX-M-1 (28.4%) and CTX-M-14 (5.6%) were the most common ESBL types. Especially, CTX-M-15 was associated with E. coli ST131 of phylogenetic group B2, which was the dominant sequence type among our isolates (35.8%). MLST typing revealed 40 different sequence types (STs), with ST131, ST410, ST10 and ST38 as the most prevalent ones. Our findings give an overview of the current distribution of ESBL-producing E. coli isolates from humans in Germany. E. coli O25b:H4-ST131 was confirmed to be the most common clone, which is known for its successful dissemination worldwide. Although heterogeneity among the isolates was found, several successful clones previously described in animals (ST410, ST10) also occurred in our isolate collection. Further detailed investigations of ESBL-producing isolates from different habitats are needed to evaluate possible transfer ways.

Emergence of extended-spectrum β-lactamase (ESBL) CTX-M-8 in Germany

(20 min) with the inactivator, using the same reporter substrate. Inactivation by clavulanic acid was observed only after preincubation competitive assays (indirect IC501⁄456 mM). On the other hand, 3-phenyl boronic acid showed enzymatic inactivation in both competitive and pre-incubation assays at high concentrations (direct IC501⁄4390 mM and indirect IC501⁄4151 mM). INQ-1 seems to be a cephalosporinase compatible with b-lactamases belonging to group 1 of the functional classification scheme. Although INQ-1 may not explain by itself all the observed resistance to b-lactams in the clinical isolate of I. limosus, it contributes to the overall increase in MICs for the INQ-1-producing E. coli clone, even if transcriptional and post-transcriptional impairments are due to the unusual start codon and high GC.

Regional distribution of nosocomial infections due to ESBL-positive Enterobacteriaceae in Germany: data from the German National Reference Center for the Surveillance of Nosocomial Infections (KISS)

Surveillance systems for hospital infections are reporting increasing rates of extended-spectrum β-lactamase (ESBL)-positive Enterobacteriaceae in Europe. We aimed to perform a national survey on this trend and on the regional distribution of nosocomial infections due to ESBL-positive Enterobacteriaceae in German hospitals. Data from 2007 to 2012 from two components of the German national nosocomial infection surveillance system were used for this analysis. The data derive from intensive care units and surgical departments. Independent factors determining the proportion of ESBL-positive Enterobacteriaceae among nosocomial infections due to Enterobacteriaceae and changes in its regional distribution (broken down into German federal states) were calculated by regression analysis. From 2007 to 2012, the data showed a significantly increasing proportion of ESBL-positive Enterobacteriaceae in surgical site infections (from 11.46 to 15.38, 134%, p 0.003), urinary tract infections (9.36 to 16.56, 177%, p <0.001) and lower respiratory tract infections (11.91 to 14.70, 123%, p <0.001) due to Enterobacteriaceae. Factors independently associated with a growing proportion were: Thuringia (p 0.009; odds ratio (OR) 1.53), North Rhine-Westphalia (p <0.001; OR 1.41) and general surgery ward (p 0.002; OR 1.47). The proportion of ESBL-positive Enterobacteriaceae in nosocomial infections has significantly increased in Germany over the last 6 years. Hospitals in Central Germany and surgical departments in all of Germany are especially affected by this development.

Attributable costs of ventilator-associated lower respiratory tract infection (LRTI) acquired on intensive care units: a retrospectively matched cohort study

BackgroundLower respiratory tract infections (LRTI) are the most common hospital-acquired infections on ICUs. They have not only an impact on each patient’s individual health but also result in a considerable financial burden for the healthcare system. Our aim was to determine the costs and the length of stay of patients with ICU-acquired LRTI.MethodsWe used a retrospectively matched cohort design, comparing patients with ICU-acquired LRTI and ICU patients without LRTI. LRTI was diagnosed using the definitions of the Centers for Disease Control and Prevention (CDC). Study period was from January to December 2010 analyzing patients from 10 different ICUs (medical, surgical, interdisciplinary). The device utilization ratio was defined as number of ventilator days divided by number of patient days and the device-associated LRTI rate was defined as number of ventilator associated LRTI divided by number of ventilator days. Patients were matched by age, sex, and prospectively obtained Simplified Acute Physiology Score II (SAPS II). The length of ICU stay of control patients needed to be at least as long as that of LRTI-patients before onset of LRTI. We used the Wilcoxon signed-rank test for continuous variables and the McNemar’s test for categorical variables.ResultsThe analyzed ICUs had 40,772 patient days in the study period with a median ventilation utilization ratio of 56 (IQR 42–65). The median device-associated LRTI rate was 3.35 (IQR 0.96-5.36) per 1,000 ventilation days. We analyzed 49 patients with ICU-acquired LRTI and 49 respective controls without LRTI. The median hospital costs for LRTI patients were significantly higher than for patients without LRTI (45,041 € vs. 26,467 €; p < .001). The attributable costs per LRTI patient were 17,015 € (p < .001). Patients with ICU acquired LRTI stayed longer in the hospital than patients without (36 days vs. 24 days; p = 0.011). An LRTI lead to an attributable increase in length of stay by 9 days (p = 0.011).ConclusionsICU-acquired LRTI is associated with increased hospital costs and prolonged hospital stay. Hospital management should therefore implement control measurements to keep the incidence of ICU-acquired LRTI as low as possible.

The impact of staffing on central venous catheter-associated bloodstream infections in preterm neonates – results of nation-wide cohort study in Germany

BackgroundVery low birthweight (VLBW) newborns on neonatal intensive care units (NICU) are at increased risk for developing central venous catheter-associated bloodstream infections (CVC BSI). In addition to the established intrinsic risk factors of VLBW newborns, it is still not clear which process and structure parameters within NICUs influence the prevalence of CVC BSI.MethodsThe study population consisted of VLBW newborns from NICUs that participated in the German nosocomial infection surveillance system for preterm infants (NEO-KISS) from January 2008 to June 2009. Structure and process parameters of NICUs were obtained by a questionnaire-based enquiry. Patient based date and the occurrence of BSI derived from the NEO-KISS database. The association between the requested parameters and the occurrance of CVC BSI and laboratory-confirmed BSI was analyzed by generalized estimating equations.ResultsWe analyzed data on 5,586 VLBW infants from 108 NICUs and found 954 BSI cases in 847 infants. Of all BSI cases, 414 (43%) were CVC-associated. The pooled incidence density of CVC BSI was 8.3 per 1,000 CVC days. The pooled CVC utilization ratio was 24.3 CVC-days per 100 patient days. A low realized staffing rate lead to an increased risk of CVC BSI (OR 1.47; p=0.008) and also of laboratory-confirmed CVC BSI (OR 1.78; p=0.028).ConclusionsOur findings show that low levels of realized staffing are associated with increased rates of CVC BSI on NICUs. Further studies are necessary to determine a threshold that should not be undercut.

Molecular epidemiology of extended-spectrum beta-lactamase (ESBL)-positive Klebsiella pneumoniae from bloodstream infections and risk factors for mortality.

The prevalence of extended-spectrum beta-lactamase (ESBL)-positive Klebsiella pneumoniae is growing worldwide. Infections with these bacteria are suspected to be related to increased mortality. We aimed to estimate the distribution of ESBL genotypes and to assess the impact on mortality associated with ESBL positivity in cases of bloodstream infection (BSI) due to K. pneumoniae. We performed a cohort study on patients with K. pneumoniae BSI between 2008 and 2011. Presence of ESBL genes was analyzed by PCR and sequencing. Risk factors for mortality were analyzed by Cox-proportional hazard regression. We identified 286 ESBL-negative (81%) and 66 (19%) ESBL-positive cases. 97% (n = 64) of the ESBL-positive isolates were susceptible for meropenem. The most common ESBL genotypes were CTX-M-15 (60%), SHV-5 (27%) and CTX-M-3 (5%). Significant risk factors for mortality were chronic pulmonary disease (HR 1.747) and moderate/severe renal disease (HR 2.572). ESBL positivity was not associated with increased mortality.

Mortality and molecular epidemiology associated with extended-spectrum β-lactamase production in Escherichia coli from bloodstream infection

Background The rate of infections due to extended-spectrum β-lactamase (ESBL)-producing Escherichia coli is growing worldwide. These infections are suspected to be related to increased mortality. We aimed to estimate the difference in mortality due to bloodstream infections (BSIs) with ESBL-positive and ESBL-negative E. coli isolates and to determine the molecular epidemiology of our ESBL-positive isolates. Materials and methods We performed a cohort study on consecutive patients with E. coli BSI between 2008 and 2010 at the Charité University Hospital. Collected data were ESBL production, basic demographic parameters, and underlying diseases by the Charlson comorbidity index (CCI). The presence of ESBL genes was analyzed by polymerase chain reaction (PCR) and sequencing. Phylogenetic groups of ESBL-positive E. coli were determined by PCR. Risk factors for mortality were analyzed by multivariable regression analysis. Results We identified 115 patients with BSI due to E. coli with ESBL phenotype and 983 due to ESBL-negative E. coli. Fifty-eight percent (n=67) of the ESBL-positive BSIs were hospital-acquired. Among the 99 isolates that were available for PCR screening and sequencing, we found mainly 87 CTX-M producers, with CTX-M-15 (n=55) and CTX-M-1 (n=21) as the most common types. Parameters significantly associated with mortality were age, CCI, and length of stay before and after onset of BSI. Conclusion The most common ESBL genotypes in clinical isolates from E. coli BSIs were CTX-M-15 (58%) and CTX-M-1 (22%). ESBL production in clinical E. coli BSI isolates was not related to increased mortality. However, the common occurrence of hospital-acquired BSI due to ESBL-positive E. coli indicates future challenges for hospitals.