contaminated sinks and contamination of ultra-filtrate bags as possible route of transmission?

Background We report on an outbreak in a surgical, interdisciplinary intensive care unit (ICU) of a tertiary care hospital. We detected a cluster of ICU patients colonized or infected with multidrug-resistant Pseudomonas aeruginosa. We established an outbreak investigation team, performed an exploratory epidemiological analysis and initiated an epidemiology-based intervention. Methods As part of the outbreak investigation, we performed microbiological examinations of the sinks in the patient rooms and a retrospective case-control study. All patients admitted to the outbreak ICU between January 2012 and February 2014 were included. Cases were patients colonized with the outbreak strain. Controls were patients with a different Pseudomonas aeruginosa strain. Risk factors were evaluated using multivariable conditional logistic regression analysis. Strain typing was performed using the repetitive element-based polymerase chain reaction (rep-PCR) DiversiLab system. Results The outbreak strain was found in the sinks of five (of 16) patient rooms. Altogether 21 cases and 21 (randomly selected) controls were included. In the univariate analysis, there was no significant difference in baseline data of the patients. In the multivariate analysis, stay in a room with a colonized sink (Odds Ratio[OR] 11.2, p = 0.007) and hemofiltration (OR 21.9, p = 0.020) were independently associated with an elevated risk for colonization or infection by the outbreak strain. In a subsequent evaluation of the work procedures associated with hemofiltration, we found that the ultra-filtrate bags had been on average five times per day emptied in the sinks of the patient rooms and were used multiple for the same patient. We exchanged the traps of the contaminated sinks and eliminated work procedures involving sinks in patient rooms by implementation of single use bags, which are emptied outside patient rooms to reduce splash water at the sinks. In the 20 month follow-up period, the outbreak strain was detected only once, which indicated that the outbreak had been ceased (incidence 0.75% vs. 0.04%, p < 0.001) Furthermore, the incidence of Pseudonomas aeruginosa overall was significantly decreased (2.5% vs. 1.5%, p < 0.001). Conclusion In ICUs, limiting work processes involving sinks results in reduced multidrug-resistant Pseudomonas aeruginosa rates. ICUs with high rates of Pseudomonas aeruginosa should consider eliminating work processes that involve sinks and potentially splash water in close proximity to patients. Trial registration All data were surveillance based data which were obtained within the German Law on Protection against Infection (“Infektionsschutzgesetz”). Therefore a trial registration was not required

An ecologic study

Background: Vancomycin-resistant enterococci (VRE) are among the most common antimicrobial-resistant pathogens causing nosocomial infections. Although antibiotic use has been identified as a risk factor for VRE, it remains unclear which antimicrobial agents particularly facilitate VRE selection. Here, we assessed whether use of specific antimicrobial agents is independently associated with healthcare-associated (HA) VRE rates in a university hospital setting in Berlin, Germany . Methods: We conducted the study between January 2014 and December 2015 at the Charité-university hospital of Berlin, Germany. From the hospital pharmacy, we extracted data for all antibacterials for systemic use (anatomical therapeutic chemical (ATC)-classification J01) and calculated ward specific antibiotic consumption in defined daily doses (DDDs) per 100 patient-days (PD). We used the microbiology laboratory database to identify all patients with isolation of invasive or non-invasive VRE and calculated HA-VRE incidence as nosocomial VRE-cases per 100 patients and HA-VRE incidence density as nosocomial VRE- cases per 1000 PD. We defined VRE isolates as hospital-acquired if they were identified three days or later after hospital admission and otherwise as community-acquired (CA-VRE). We performed univariable and multivariable regression analyses to estimate the association of the frequency of HA-VRE per month with antibiotic use and other parameters such as length of stay, type of ward or presence of at least one CA-VRE on ward. In a second analysis, we considered only patients with VRE infections. Results: We included data from 204,054 patients with 948,380 PD from 61 wards. Overall, 1430 VRE-cases were identified of which 409 (28.6%) were considered hospital-acquired (HA). We found that carbapenem use in the current month and prior-month use of glycopeptides increased the risk for HA-VRE by 1% per 1 DDD/100 PD and 3% per 1 DDD/100 PD, respectively. However, when only VRE from clinical samples were considered, only glycopeptide use showed a statistically significant association. In both models, detection of at least one patient with CA-VRE on a ward in the current month significantly increased the risk of HA-VRE, thereby indicating nosocomial spread of VRE. Conclusions: Our findings suggest that the risk of HA-VRE is associated with specific antimicrobial agents. Prudent use of these antimicrobial agents might reduce nosocomial VRE rates. That appearance of at least one CA-VRE case on the ward increased the risk of HA-VRE detection highlights the importance of strict hand hygiene practices to interrupt person-to-person transmission of VRE

Validation of a New PCR-Based Screening Method for Prevention of Serratia marcescens Outbreaks in the Neonatal Intensive Care Unit

Background: Serratia marcescens may cause severe nosocomial infections, mostly in very low birth weight infants. Since S. marcescens exhibits by far the highest adjusted incidence rate for horizontal transmission, it can cause complex outbreak situations in neonatal intensive care units. Objective: The aim of this study was to establish a fast and highly sensitive colonization screening for prompt cohorting and barrier nursing strategies. Methods: A probe-based duplex PCR assay targeting the 16S rRNA gene of S. marcescens was developed and validated by using 36 reference strains, 14 S. marcescens outbreak- and nonoutbreak isolates, defined by epidemiological linkage and molecular typing, and applied in 1,347 clinical specimens from 505 patients. Results and Conclusions: The novel PCR assay proved to be highly specific and had an in vitro sensitivity of 100 gene copies per reaction (similar to 15 bacteria). It showed a similar (in laryngeal/tracheal specimens) or even higher (in rectal/stoma swabs) in vivo sensitivity in comparison to routine microbial culture and was much quicker (<24 h vs. 2 days). By combining different oligonucleotide primers, there was robust detection of genetic variants of S. marcescens strains. PCR inhibition was low (1.6%) and observed with rectal swabs only. Cohort analysis illustrated applicability of the PCR assay as a quick tool to prevent outbreak scenarios by allowing rapid decisions on cohorting and barrier nursing. In summary, this novel molecular screening for colonization by S. marcescens is specific, highly sensitive, and substantially accelerates detection

Validation of a New PCR-Based Screening Method for Prevention of Serratia marcescens Outbreaks in the Neonatal Intensive Care Unit

Background: Serratia marcescens may cause severe nosocomial infections, mostly in very low birth weight infants. Since S. marcescens exhibits by far the highest adjusted incidence rate for horizontal transmission, it can cause complex outbreak situations in neonatal intensive care units. Objective: The aim of this study was to establish a fast and highly sensitive colonization screening for prompt cohorting and barrier nursing strategies. Methods: A probe-based duplex PCR assay targeting the 16S rRNA gene of S. marcescens was developed and validated by using 36 reference strains, 14 S. marcescens outbreak- and nonoutbreak isolates, defined by epidemiological linkage and molecular typing, and applied in 1,347 clinical specimens from 505 patients. Results and Conclusions: The novel PCR assay proved to be highly specific and had an in vitro sensitivity of 100 gene copies per reaction (∼15 bacteria). It showed a similar (in laryngeal/tracheal specimens) or even higher (in rectal/stoma swabs) in vivo sensitivity in comparison to routine microbial culture and was much quicker (<24 h vs. 2 days). By combining different oligonucleotide primers, there was robust detection of genetic variants of S. marcescens strains. PCR inhibition was low (1.6%) and observed with rectal swabs only. Cohort analysis illustrated applicability of the PCR assay as a quick tool to prevent outbreak scenarios by allowing rapid decisions on cohorting and barrier nursing. In summary, this novel molecular screening for colonization by S. marcescens is specific, highly sensitive, and substantially accelerates detection

An outbreak of carbapenem-resistant OXA-48 – producing Klebsiella pneumonia associated to duodenoscopy

Background Carbapenemase-producing Enterobacteriaceae (CPE) have become a major problem for healthcare systems worldwide. While the first reports from European hospitals described the introduction of CPE from endemic countries, there is now a growing number of reports describing outbreaks of CPE in European hospitals. Here we report an outbreak of Carbapenem-resistant K. pneumoniae in a German University hospital which was in part associated to duodenoscopy. Findings Between December 6, 2012 and January 10, 2013, carbapenem-resistant K. pneumoniae (CRKP) was cultured from 12 patients staying on 4 different wards. The amplification of carbapenemase genes by multiplex PCR showed presence of the bla OXA-48 gene. Molecular typing confirmed the identity of all 12 isolates. Reviewing the medical records of CRKP cases revealed that there was a spatial relationship between 6 of the cases which were located on the same wards. The remaining 6 cases were all related to endoscopic retrograde cholangiopancreatography (ERCP) which was performed with the same duodenoscope. The outbreak ended after the endoscope was sent to the manufacturer for maintenance. Conclusions Though the outbreak strain was also disseminated to patients who did not undergo ERCP and environmental sources or medical personnel also contributed to the outbreak, the gut of colonized patients is the main source for CPE. Therefore, accurate and stringent reprocessing of endoscopic instruments is extremely important, which is especially true for more complex instruments like the duodenoscope (TJF Q180V series) involved in the outbreak described here

Sepsis Caused by Extended-Spectrum Beta-Lactamase (ESBL)-Positive K. pneumoniae and E. coli: Comparison of Severity of Sepsis, Delay of Anti- Infective Therapy and ESBL Genotype

Infections with extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E) are associated with increased mortality. Outcome differences due to various species of ESBL-E or ESBL genotypes are not well investigated. We conducted a cohort study to assess risk factors for mortality in cases of ESBL-E bacteremia (K. pneumoniae or E. coli) and the risk factors for sepsis with organ failure. All consecutive patients of our institution from 2008 to 2011 with bacteremia due to ESBL-E were included. Basic epidemiological data, underlying comorbidities, origin of bacteremia, severity of sepsis and delay of appropriate anti-infective treatment were collected. Isolates were PCR- screened for the presence of ESBL genes and plasmid-mediated AmpC β-lactamases. Cox proportional hazard regression on mortality and multivariable logistic regression on risk factors for sepsis with organ failure was conducted. 219 cases were included in the analysis: 73.1% due to E. coli, 26.9% due to K. pneumoniae. There was no significant difference in hospital mortality (ESBL-E. coli, 23.8% vs. ESBL-K. pneumoniae 27.1%, p = 0.724). However, the risk of sepsis with organ failure was associated in cases of K. pneumoniae bacteremia (OR 4.5, p<0.001) and patients with liver disease (OR 3.4, p = 0.004) or renal disease (OR 6.8, p<0.001). We found significant differences in clinical presentation of ESBL-E bacteremia due to K. pneumoniae compared to E. coli. As K. pneumoniae cases showed a more serious clinical presentation as E. coli cases and were associated with different risk factors, treatment and prevention strategies should be adjusted accordingly

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

Outpatient decolonization after recurrent skin infection with Panton-Valentine leukocidin (PVL)-producing S. aureus - The importance of treatment repetition

Background: Recurrent skin abscesses are often associated with Panton-Valentine leukocidin-producing strains of S. aureus (PVL-SA). Decolonization measures are required along with treatment of active infections to prevent re-infection and spreading. Even though most PVL-SA patients are treated as outpatients, there are few studies that assess the effectiveness of outpatient topical decolonization in PVL-SA patients. Methods: We assessed the results of topical decolonization of PVL-SA in a retrospective review of patient files and personal interviews. Successful decolonization was defined as the absence of any skin abscesses for at least 6 months after completion of the final decolonization treatment. Clinical and demographic data was assessed. An intention-to-treat protocol was used. Results: Our cohort consisted of 115 symptomatic patients, 66% from PVL-positive MSSA and 19% from PVL-positive MRSA. The remaining 16% consisted of symptomatic patients with close contact to PVL-SA positive index patients but without detection of PVL-SA. The majority of patients were female (66%). The median age was 29.87% of the patients lived in multiple person households. Our results showed a 48% reduction in symptomatic PVL-SA cases after the first decolonization treatment. The results also showed that the decrease continued with each repeated decolonization treatment and reached 89% following the 5th treatment. A built multivariable Cox proportional-hazards model showed that the absence of PVL-SA detection (OR 2.0) and living in single person households (OR 2.4) were associated with an independently increased chance of successful decolonization. Conclusion: In our cohort, topical decolonization was a successful preventive measure for reducing the risk of PVL-SA skin abscesses in the outpatient setting. Special attention should be given to patients living in multiple person households because these settings could confer a risk that decolonization will not be successful

Plasmid-Mediated Transmission of KPC-2 Carbapenemase in Enterobacteriaceae in Critically III Patients

Carbapenem-resistant Enterobacteriaceae (CRE) cause health care-associated infections worldwide, and they are of severe concern due to limited treatment options. We report an outbreak of KPC-2-producing CRE that was caused by horizontal transmission of a promiscuous plasmid across different genera of bacteria and hospitals in Germany. Eleven isolates (8 Citrobacter freundii, 2 Klebsiella oxytoca, and 1 Escherichia coli) were obtained from seven critically ill patients during the six months of the outbreak in 2016. One patient developed a CRE infection while the other six patients were CRE-colonized. Three patients died in the course of the hospital stay. Six of the seven patients carried the same C. freundii clone; one K. oxytoca clone was found in two patients, and one patient carried E. coli and C. freundii. Molecular analysis confirmed the presence of a conjugative, blaKPC-2-carrying 70 kb-IncN plasmid in C. freundii and E. coli and an 80 kb-IncN plasmid in K. oxytoca. All transconjugants harbored either the 70 or 80 kb plasmid with blaKPC-2, embedded within transposon variant Tn4401g. Whole genome sequencing and downstream bioinformatics analyses of all plasmid sequences showed an almost perfect match when compared to a blaKPC-2-carrying plasmid of a large outbreak in another German hospital two years earlier. Differences in plasmid sizes and open reading frames point to the presence of inserted mobile genetic elements. There are few outbreak reports worldwide on the transmission of blaKPC-2-carrying plasmids across different bacterial genera. Our data suggest a regional and supraregional spread of blaKPC-2-carrying IncN-plasmids harboring the Tn4401g isoform in Germany.</p

Plasmid-Mediated Transmission of KPC-2 Carbapenemase in Enterobacteriaceae in Critically Ill Patients

Carbapenem-resistant Enterobacteriaceae (CRE) cause health care-associated infections worldwide, and they are of severe concern due to limited treatment options. We report an outbreak of KPC-2-producing CRE that was caused by horizontal transmission of a promiscuous plasmid across different genera of bacteria and hospitals in Germany. Eleven isolates (8 Citrobacter freundii, 2 Klebsiella oxytoca, and 1 Escherichia coli) were obtained from seven critically ill patients during the six months of the outbreak in 2016. One patient developed a CRE infection while the other six patients were CRE-colonized. Three patients died in the course of the hospital stay. Six of the seven patients carried the same C. freundii clone; one K. oxytoca clone was found in two patients, and one patient carried E. coli and C. freundii. Molecular analysis confirmed the presence of a conjugative, blaKPC-2-carrying 70 kb-IncN plasmid in C. freundii and E. coli and an 80 kb-IncN plasmid in K. oxytoca. All transconjugants harbored either the 70 or 80 kb plasmid with blaKPC-2, embedded within transposon variant Tn4401g. Whole genome sequencing and downstream bioinformatics analyses of all plasmid sequences showed an almost perfect match when compared to a blaKPC-2-carrying plasmid of a large outbreak in another German hospital two years earlier. Differences in plasmid sizes and open reading frames point to the presence of inserted mobile genetic elements. There are few outbreak reports worldwide on the transmission of blaKPC-2-carrying plasmids across different bacterial genera. Our data suggest a regional and supraregional spread of blaKPC-2-carrying IncN-plasmids harboring the Tn4401g isoform in Germany