Gesuele Renzi

Universal screening for methicillin-resistant Staphylococcus aureus at hospital admission and nosocomial infection in surgical patients.

CONTEXT Experts and policy makers have repeatedly called for universal screening at hospital admission to reduce nosocomial methicillin-resistant Staphylococcus aureus (MRSA) infection. OBJECTIVE To determine the effect of an early MRSA detection strategy on nosocomial MRSA infection rates in surgical patients. DESIGN, SETTING, AND PATIENTS Prospective, interventional cohort study conducted between July 2004 and May 2006 among 21 754 surgical patients at a Swiss teaching hospital using a crossover design to compare 2 MRSA control strategies (rapid screening on admission plus standard infection control measures vs standard infection control alone). Twelve surgical wards including different surgical specialties were enrolled according to a prespecified agenda, assigned to either the control or intervention group for a 9-month period, then switched over to the other group for a further 9 months. INTERVENTIONS During the rapid screening intervention periods, patients admitted to the intervention wards for more than 24 hours were screened before or on admission by rapid, multiplex polymerase chain reaction. For both intervention (n=10 844) and control (n=10 910) periods, standard infection control measures were used for patients with MRSA in all wards and consisted of contact isolation of MRSA carriers, use of dedicated material (eg, gown, gloves, mask if indicated), adjustment of perioperative antibiotic prophylaxis of MRSA carriers, computerized MRSA alert system, and topical decolonization (nasal mupirocin ointment and chlorhexidine body washing) for 5 days. MAIN OUTCOME MEASURES Incidence of nosocomial MRSA infection, MRSA surgical site infection, and rates of nosocomial acquisition of MRSA. RESULTS Overall, 10 193 of 10 844 patients (94%) were screened during the intervention periods. Screening identified 515 MRSA-positive patients (5.1%), including 337 previously unknown MRSA carriers. Median time from screening to notification of test results was 22.5 hours (interquartile range, 12.2-28.2 hours). In the intervention periods, 93 patients (1.11 per 1000 patient-days) developed nosocomial MRSA infection compared with 76 in the control periods (0.91 per 1000 patient-days; adjusted incidence rate ratio, 1.20; 95% confidence interval, 0.85-1.69; P = .29). The rate of MRSA surgical site infection and nosocomial MRSA acquisition did not change significantly. Fifty-three of 93 infected patients (57%) in the intervention wards were MRSA-free on admission and developed MRSA infection during hospitalization. CONCLUSION A universal, rapid MRSA admission screening strategy did not reduce nosocomial MRSA infection in a surgical department with endemic MRSA prevalence but relatively low rates of MRSA infection. TRIAL REGISTRATION isrctn.org Identifier: ISRCTN06603006.

Evaluation of rapid screening and pre-emptive contact isolation for detecting and controlling methicillin-resistant Staphylococcus aureus in critical care: an interventional cohort study

IntroductionRapid diagnostic tests may allow early identification of previously unknown methicillin-resistant Staphylococcus aureus (MRSA) carriers at intensive care unit (ICU) admission. The aim of this study was twofold: first, to assess whether a new molecular MRSA screening test can substantially decrease the time between ICU admission and identification of MRSA carriers; and, second, to examine the combined effect of rapid testing and pre-emptive contact isolation on MRSA infections.MethodSince November 2003, patients admitted for longer than 24 hours to two adult ICUs were screened systematically on admission using quick, multiplex immunocapture-coupled PCR (qMRSA). Median time intervals from admission to notification of test results were calculated for a five-month intervention phase (November 2003–March 2004) and compared with a historical control period (April 2003–October 2003) by nonparametric tests. ICU-acquired MRSA infection rates were determined for an extended surveillance period (January 2003 through August 2005) and analyzed by Poisson regression methods.ResultsDuring the intervention phase, 97% (450/462) of patients admitted to the surgical ICU and 80% (470/591) of patients admitted to the medical ICU were screened. On-admission screening identified the prevalence of MRSA to be 6.7% (71/1053). Without admission screening, 55 previously unknown MRSA carriers would have been missed in both ICUs. Median time from ICU admission to notification of test results decreased from 87 to 21 hours in the surgical ICU (P < 0.001) and from 106 to 23 hours in the medical ICU (P < 0.001). In the surgical ICU, 1,227 pre-emptive isolation days for 245 MRSA-negative patients were saved by using the qMRSA test. After adjusting for colonization pressure, the systematic on-admission screening and pre-emptive isolation policy was associated with a reduction in medical ICU acquired MRSA infections (relative risk 0.3, 95% confidence interval 0.1–0.7) but had no effect in the surgical ICU (relative risk 1.0, 95% confidence interval 0.6–1.7).ConclusionThe qMRSA test decreased median time to notification from four days to one day and helped to identify previously unknown MRSA carriers rapidly. A strategy linking the rapid screening test to pre-emptive isolation and cohorting of MRSA patients substantially reduced MRSA cross-infections in the medical but not in the surgical ICU.

Impact of Combined Low-Level Mupirocin and Genotypic Chlorhexidine Resistance on Persistent Methicillin-Resistant Staphylococcus aureus Carriage After Decolonization Therapy: A Case-control Study

BACKGROUND The clinical importance of low-level mupirocin resistance and genotypic chlorhexidine resistance remains unclear. We aimed to determine whether resistance to these agents increases the risk of persistent methicillin-resistant Staphylococcus aureus (MRSA) carriage after their use for topical decolonization therapy. METHODS A nested case-control study was conducted of MRSA carriers who received decolonization therapy from 2001 through 2008. Cases, patients who remained colonized, were matched by year to controls, those in whom MRSA was eradicated (follow-up, 2 years). Baseline MRSA isolates were tested for mupirocin resistance by Etest and chlorhexidine resistance by qacA/B polymerase chain reaction. MRSA carriers with high-level mupirocin resistance were excluded. The effect of the primary exposure of interest, low-level mupirocin and genotypic chlorhexidine resistance, was evaluated with multivariate conditional logistic regression analysis. RESULTS The 75 case patients and 75 control patients were similar except that those persistently colonized were older (P = .007) with longer lengths of hospital stay (P = .001). After multivariate analysis, carriage of combined low-level mupirocin and genotypic chlorhexidine resistance before decolonization independently predicted persistent MRSA carriage (odds ratio [OR], 3.4 [95% confidence interval {CI}, 1.5-7.8]). Other risk factors were older age (OR, 1.04 [95% CI, 1.02-1.1]), previous hospitalization (OR, 2.4 [95% CI, 1.1-5.7]), presence of a skin wound (OR, 5.7 [95% CI, 1.8-17.6]), recent antibiotic use (OR, 3.1 [95% CI, 1.3-7.2]), and central venous catheterization (OR, 5.7 [95% CI, 1.4-23.9]). CONCLUSIONS Combined low-level mupirocin and genotypic chlorhexidine resistance significantly increases the risk of persistent MRSA carriage after decolonization therapy. Institutions with widespread use of these agents should monitor for resistance and loss of clinical effectiveness.

A Novel Multiplex Real-Time PCR Assay for Rapid Typing of Major Staphylococcal Cassette Chromosome mec Elements

ABSTRACT We describe a novel procedure for rapid typing of the staphylococcal cassette chromosome mec element, a molecular marker allowing discrimination between community- and hospital-acquired methicillin-resistant Staphylococcus aureus (MRSA) strains. Oligonucleotides targeting the recombinase genes were type specific and used to type a collection of 399 MRSA isolates recovered during patient screening at admission. This novel assay constitutes a valuable tool for evaluating the molecular epidemiology of MRSA and adjusting infection control strategies against MRSA.

Evaluation of Three Molecular Assays for Rapid Identification of Methicillin-Resistant Staphylococcus aureus

ABSTRACT One home-developed assay and two commercial assays for the rapid identification of methicillin-resistant Staphylococcus aureus (MRSA) were compared by use of a collection of clinical isolates displaying highly diverse genetic backgrounds. Our results suggest that users of orfX-staphylococcal cassette chromosome mec-based assays should repeatedly monitor the local epidemiology to minimize the risks of detection bias and the omission of emerging MRSA clones.

Methicillin-Resistant Staphylococcus aureus, Geneva, Switzerland, 1993–2005

Molecular characterization of methicillin-resistant Staphylococcus aureus (MRSA) strains different from those of an endemic healthcare-associated clone was conducted over 13 years in Geneva, Switzerland. We demonstrated strain diversity, including clones rarely found in Europe. Local epidemiology of community-associated MRSA is diverse and is evolving by importation and transmission of new strains.

Molecular analysis of NDM-1-producing enterobacterial isolates from Geneva, Switzerland

OBJECTIVES To analyse the mechanisms responsible for decreased susceptibility or resistance to carbapenems in several enterobacterial isolates recovered in 2009-10 in Geneva University Hospitals, Switzerland. METHODS PCR and sequencing were used to identify β-lactamases, 16S RNA methylases and plasmid-mediated quinolone resistance genes. The transferable properties of the plasmids were analysed, as well as their plasmid type. The strains were typed by multilocus sequence typing. RESULTS Three patients were found to be positive for NDM-1-producing enterobacterial isolates (one with Escherichia coli and Klebsiella pneumoniae, one with K. pneumoniae only and one with Proteus mirabilis), where NDM-1 stands for New Delhi metallo-β-lactamase-1. The bla(NDM-1) carbapenemase gene was detected in all isolates in addition to genes encoding narrow-spectrum β-lactamases (TEM-1, SHV-11, OXA-1, OXA-9 and OXA-10), extended-spectrum β-lactamases (CTX-M-15, CMY-16 and CMY-30), ArmA and quinolone resistance determinants (Qnr). The bla(NDM-1) gene was located on conjugative IncA/C- or IncF-type plasmids. Upstream of the bla(NDM-1) gene, part of ISAba125, previously identified in NDM-1-negative Acinetobacter baumannii, was found. Downstream of the bla(NDM-1) gene, variable sequences were found. CONCLUSIONS This work constitutes the first identification of NDM-1 producers in Switzerland. Interestingly, patients from whom these NDM-1-producing isolates were recovered had a link with the Indian subcontinent or the Balkans.

Use of Oligoarrays for Characterization of Community-Onset Methicillin-Resistant Staphylococcus aureus

ABSTRACT Until recently, methicillin-resistant Staphylococcus aureus (MRSA) was considered the prototype of a hospital-acquired bacterial pathogen. However, recent reports have shown that MRSA has now emerged in the community. Characterization of specific markers for distinguishing the origin of isolates could contribute to improved knowledge of MRSA epidemiology. The release of whole-genome sequences of hospital- and community-acquired S. aureus strains allowed the development of whole-genome content analysis techniques, including microarrays. We developed a microarray composed of 8,191 open reading frame-specific oligonucleotides covering >99% of the four sequenced S. aureus genomes (N315, Mu50, MW2, and COL) to evaluate gene contents of hospital- and community-onset S. aureus strains. In parallel, pulsed-field gel electrophoresis, variable number of tandem repeats, antibiogram, staphylococcal cassette chromosome-mec element typing, and presence of the Panton-Valentine leukocidin gene were evaluated in a collection of 15 clinical isolates. Clusters obtained with microarrays showed a high degree of similarity with those obtained by pulsed-field gel electrophoresis or variable number of tandem repeats. Clusters clearly segregated hospital-onset strains from community-onset strains. Moreover, the microarray approach allowed definition of novel marker genes and chromosomal regions specific for given groups of isolates, thus providing better discrimination and additional information compared to pulsed-field gel electrophoresis and variable number of tandem repeats. Finally, the comparative genome hybridization approach unraveled the occurrence of multiple horizontal transfer events leading to community-onset MRSA as well as the need for a specific genetic background in recipient strains for both the acquisition and the stability of the mec element.

Decolonization of intestinal carriage of extended-spectrum β-lactamase-producing Enterobacteriaceae with oral colistin and neomycin: a randomized, double-blind, placebo-controlled trial

OBJECTIVES Extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-E) are an increasingly frequent cause of infections in the community and the healthcare setting. In this study, we aimed to investigate whether intestinal carriage of ESBL-E can be eradicated. METHODS We conducted a double-blind, randomized, placebo-controlled, single-centre trial to assess the efficacy of an oral decolonization regimen on intestinal ESBL-E carriage in adult patients with an ESBL-E-positive rectal swab. Fifty-eight patients were allocated 1 : 1 to either placebo or colistin sulphate (50 mg 4×/day) and neomycin sulphate (250 mg 4×/day) for 10 days plus nitrofurantoin (100 mg 3×/day) for 5 days in the presence of ESBL-E bacteriuria. The primary outcome was detection of ESBL-E by rectal swab 28 ± 7 days after the end of treatment. Missing primary outcome data were imputed based on the last available observation. Additional cultures (rectal, inguinal and urine) were taken on day 6 of treatment and on days 1 and 7 post-treatment. The study protocol has been registered with ClinicalTrials.gov (NCT00826670). RESULTS Among 54 patients (27 in each group) included in the primary analysis, there was no statistically significant difference between the groups with regard to the primary outcome [14/27 (52%) versus 10/27 (37%), P = 0.27]. During treatment and shortly afterwards, there was significantly lower rectal ESBL-E carriage in the treatment group: 9/26 versus 19/22 on day 6 of treatment (P < 0.001) and 8/25 versus 20/26 on day 1 post-treatment (P = 0.001). This effect had disappeared by day 7 post-treatment (18/27 versus 17/25, P = 0.92). Liquid stools were more common in the treatment group (7/27 versus 2/29, P = 0.05). CONCLUSIONS The regimen used in this study temporarily suppressed ESBL-E carriage, but had no long-term effect.

A Predictive Model for Identifying Surgical Patients at Risk of Methicillin-Resistant Staphylococcus aureus Carriage on Admission

BACKGROUND Legislative mandates and current guidelines for control of nosocomial transmission of methicillin-resistant Staphylococcus aureus (MRSA) recommend screening of patients at risk of MRSA carriage on hospital admission. Indiscriminate application of these guidelines can result in a large number of unnecessary screening tests. STUDY DESIGN This study was conducted to develop and validate a prediction model to define surgical patients at risk of previously unknown MRSA carriage on admission. We used data from two prospective studies to derivate and validate predictors of previously unknown MRSA carriage on admission, using logistic regression analysis. RESULTS A total of 13,262 patients (derivation cohort, 3,069; validation cohort, 10,193) were admitted to the surgery department and screened for MRSA. Prevalence of MRSA carriage at time of admission increased from 3.2% in 2003 to 5.1% in the period 2004 to 2006, with a majority of newly identified MRSA carriers (64%). Three independent factors were correlated with previously unknown MRSA carriage: recent antibiotic treatment (adjusted odds ratio [OR]: 4.5; p < 0.001), history of hospitalization (adjusted OR: 2.7; p = 0.03), and age older than 75 years (adjusted OR: 1.9; p = 0.048). A score (range 0 to 9 points) calculated from these variables was developed. Probability of previously unknown MRSA carriage was 5% (8 of 152) in patients with a low score (< 2 points), 11% (19 of 166) in those with an intermediate score (2 to 6 points), and 34% (30 of 87) in those with a high score (> or = 7 points). Limiting screening to patients with all 3 risk factors (21% and 26% of patients in the derivation and validation cohort, respectively) would have correctly identified 53% and 37% of MRSA carriers in both cohorts. CONCLUSIONS A predictive model using three easily retrievable determinants might help to better target surgical patients at risk of MRSA carriage on admission.