Nathalie Vernaz

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.

Temporal effects of antibiotic use and hand rub consumption on the incidence of MRSA and Clostridium difficile

OBJECTIVES The aim of this study was to determine the temporal relation between the use of antibiotics and alcohol-based hand rubs (ABHRs) and the incidence of methicillin-resistant Staphylococcus aureus (MRSA) and Clostridium difficile. METHODS An interventional time-series analysis was performed to evaluate the impact of two promotion campaigns on the consumption of ABHRs and to assess their effect on the incidence of non-duplicate clinical isolates of MRSA and C. difficile from February 2000 through September 2006. This analysis was combined with a transfer function model of aggregated data on antibiotic use. RESULTS Consumption of ABHRs correlated with MRSA, but not with C. difficile. The final model demonstrated the immediate effect of the second hand hygiene promotion campaign and an additional temporal effect of fluoroquinolone (time lag, 1 month; i.e. antibiotic effect delayed for 1 month), macrolide (lag 1 and 4 months), broad-spectrum cephalosporins (lag 3, 4 and 5 months) and piperacillin/tazobactam (lag 3 months) use. The final model explained 57% of the MRSA variance over time. In contrast, the model for C. difficile showed only an effect for broad-spectrum cephalosporins (lag 1 month). CONCLUSIONS We observed an aggregate-level relation between the monthly MRSA incidence and the use of different antibiotic classes and increased consumption of ABHR after a successful hand hygiene campaign, while no association with ABHR use was detected for C. difficile.

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.

Multihospital Outbreak of Clostridium difficile Ribotype 027 Infection: Epidemiology and Analysis of Control Measures

OBJECTIVE To report a large outbreak of Clostridium difficile infection (CDI; ribotype 027) between June 2007 and August 2008, describe infection control measures, and evaluate the impact of restricting the use of fluoroquinolones in controlling the outbreak. DESIGN Outbreak investigation in 3 acute care hospitals of the Northern Health and Social Care Trust in Northern Ireland. INTERVENTIONS Implementation of a series of CDI control measures that targeted high-risk antibiotic agents (ie, restriction of fluoroquinolones), infection control practices, and environmental hygiene. RESULTS A total of 318 cases of CDI were identified during the outbreak, which was the result of the interaction between C. difficile ribotype 027 being introduced into the affected hospitals for the first time and other predisposing risk factors (ranging from host factors to suboptimal compliance with antibiotic guidelines and infection control policies). The 30-day all-cause mortality rate was 24.5%; however, CDI was the attributable cause of death for only 2.5% of the infected patients. Time series analysis showed that restricting the use of fluoroquinolones was associated with a significant reduction in the incidence of CDI (coefficient, -0.054; lag time, 4 months; P = .003). CONCLUSION These findings provide additional evidence to support the value of antimicrobial stewardship as an essential element of multifaceted interventions to control CDI outbreaks. The present CDI outbreak was ended following the implementation of an action plan improving communication, antibiotic stewardship, infection control practices, environmental hygiene, and surveillance.

Modelling the impact of antibiotic use on antibiotic-resistant Escherichia coli using population-based data from a large hospital and its surrounding community

OBJECTIVES To determine the temporal relationship between antibiotic use and incidence of antibiotic-resistant Escherichia coli in both the inpatient and outpatient setting of a large urban area. METHODS A retrospective observational time-series analysis was performed to evaluate the incidence of non-duplicate clinical isolates of E. coli resistant to ciprofloxacin, trimethoprim/sulfamethoxazole and cefepime from January 2000 through December 2007, combined with a transfer function model of aggregated data on antibiotic use in both settings obtained from the hospitals pharmacy and outpatient billing offices. RESULTS Ciprofloxacin resistance increased from 6.0% (2000) to 15.4% (2007; P<0.0001) and cefepime resistance from 0.9% (2002) to 3.2% (2007; P=0.01). Trimethoprim/sulfamethoxazole resistance remained stable (23.7%-25.8%). Total antibiotic use increased in both settings, while fluoroquinolone use increased significantly only among outpatients. A temporal effect between fluoroquinolone resistance in community E. coli isolates and outpatient use of ciprofloxacin (immediate effect and time lag 1 month) and moxifloxacin (time lag 4 months) was observed, explaining 51% of the variance over time. The incidence of cefepime resistance in E. coli was correlated with ciprofloxacin use in the inpatient (lag 1 month) and outpatient (lag 4 months) settings and with the use of ceftriaxone (lag 0 month), piperacillin/tazobactam (3 months) and cefepime (3 months) in the hospital (R2=51%). CONCLUSIONS These results support efforts to reduce prescribing of fluoroquinolones for control of resistant E. coli including extended-spectrum β-lactamase producers and show the added value of time-series analysis to better understand the interaction between community and hospital antibiotic prescribing and its spill-over effect on antibiotic resistance.

The impact of antibiotic use on the incidence and resistance pattern of extended‐spectrum beta‐lactamase‐producing bacteria in primary and secondary healthcare settings

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • The emergence and spread of bacteria producing extended-spectrum beta-lactamases (ESBLs) has important therapeutic and epidemiologic implications. • A key target for the establishment of hospital antibiotic stewardship is reducing the occurrence of additional antibiotic resistance. • Further research is needed to accumulate supporting evidence that reducing antibiotic use will result in a parallel reduction in antibiotic resistance. WHAT THIS STUDY ADDS • Fluoroquinolone restriction reversed ciprofloxacin resistance in primary and secondary healthcare settings. • Fluoroquinolone restriction reduced ESBL-producing bacteria incidence rates in both the primary and secondary healthcare settings. • This study highlights the value of time-series analysis in designing efficient antibiotic stewardship. AIMS The objective of the present study was to study the relationship between hospital antibiotic use, community antibiotic use and the incidence of extended-spectrum beta-lactamase (ESBL)-producing bacteria in hospitals, while assessing the impact of a fluoroquinolone restriction policy on ESBL-producing bacteria incidence rates. METHODS The study was retrospective and ecological in design. A multivariate autoregressive integrated moving average (ARIMA) model was built to relate antibiotic use to ESB-producing bacteria incidence rates and resistance patterns over a 5 year period (January 2005-December 2009). RESULTS Analysis showed that the hospital incidence of ESBLs had a positive relationship with the use of fluoroquinolones in the hospital (coefficient = 0.174, P= 0.02), amoxicillin-clavulanic acid in the community (coefficient = 1.03, P= 0.03) and mean co-morbidity scores for hospitalized patients (coefficient = 2.15, P= 0.03) with various time lags. The fluoroquinolone restriction policy was implemented successfully with the mean use of fluoroquinolones (mainly ciprofloxacin) being reduced from 133 to 17 defined daily doses (DDDs)/1000 bed days (P < 0.001) and from 0.65 to 0.54 DDDs/1000 inhabitants/day (P= 0.0007), in both the hospital and its surrounding community, respectively. This was associated with an improved ciprofloxacin susceptibility in both settings [ciprofloxacin susceptibility being improved from 16% to 28% in the community (P < 0.001)] and with a statistically significant reduction in ESBL-producing bacteria incidence rates. DISCUSSION This study supports the value of restricting the use of certain antimicrobial classes to control ESBL, and demonstrates the feasibility of reversing resistance patterns post successful antibiotic restriction. The study also highlights the potential value of the time-series analysis in designing efficient antibiotic stewardship.

Quasiexperimental Study of the Effects of Antibiotic Use, Gastric Acid-Suppressive Agents, and Infection Control Practices on the Incidence of Clostridium difficile-Associated Diarrhea in Hospitalized Patients

ABSTRACT The objective of this study was to evaluate the effects of antimicrobial drug use, gastric acid-suppressive agent use, and infection control practices on the incidence of Clostridium difficile-associated diarrhea (CDAD) in a 426-bed general teaching hospital in Northern Ireland. The study was retrospective and ecological in design. A multivariate autoregressive integrated moving average (time-series analysis) model was built to relate CDAD incidence with antibiotic use, gastric acid-suppressive agent use, and infection control practices within the hospital over a 5-year period (February 2002 to March 2007). The findings of this study showed that temporal variation in CDAD incidence followed temporal variations in expanded-spectrum cephalosporin use (average delay = 2 months; variation of CDAD incidence = 0.01/100 bed-days), broad-spectrum cephalosporin use (average delay = 2 months; variation of CDAD incidence = 0.02/100 bed-days), fluoroquinolone use (average delay = 3 months; variation of CDAD incidence = 0.004/100 bed-days), amoxicillin-clavulanic acid use (average delay = 1 month; variation of CDAD incidence = 0.002/100 bed-days), and macrolide use (average delay = 5 months; variation of CDAD incidence = 0.002/100 bed-days). Temporal relationships were also observed between CDAD incidence and use of histamine-2 receptor antagonists (H2RAs; average delay = 1 month; variation of CDAD incidence = 0.001/100 bed-days). The model explained 78% of the variance in the monthly incidence of CDAD. The findings of this study highlight a temporal relationship between certain classes of antibiotics, H2RAs, and CDAD incidence. The results of this research can help hospitals to set priorities for restricting the use of specific antibiotic classes, based on the size-effect of each class and the delay necessary to observe an effect.

Temporal effects of antibiotic use and Clostridium difficile infections

OBJECTIVES We tested a previously published model for the analysis of the temporal relationship between antibiotic use and the incidence of Clostridium difficile infection in a hospital with stable incidence of infection at >1 case per 1000 admissions per month. METHODS The study period was from April 2004 to June 2008 and used data from Infection Control and Hospital Pharmacy. We first described the monthly variation in C. difficile infection and then constructed a multivariate transfer function model that included lag time (cases of C. difficile infection in previous months and delays between changes in antibiotic use and changes in C. difficile infection). RESULTS The average incidence of C. difficile infection was 1.5 cases per 1000 patients per month with no significant increase over 3 years. The number of cases of C. difficile infection in 1 month was dependent on the average number of cases of C. difficile infection in the previous 2 months. The models with data from the whole hospital showed a statistically significant relationship between the number of both hospital-acquired C. difficile infections and total C. difficile infections and consumption of piperacillin/tazobactam, ciprofloxacin and cefuroxime. The association between C. difficile infection and consumption of co-amoxiclav was only significant for hospital-acquired C. difficile infection. The model for hospital-acquired C. difficile infections explained 61% of the variance in C. difficile infections. CONCLUSIONS These results provide support for antibiotic policies that minimize the use of broad-spectrum penicillins (co-amoxiclav and piperacillin/tazobactam), cephalosporins and fluoroquinolones.

Temporal Variability of Antibiotics Fluxes in Wastewater and Contribution from Hospitals

Significant quantities of antibiotics are used in all parts of the globe to treat diseases with bacterial origins. After ingestion, antibiotics are excreted by the patient and transmitted in due course to the aquatic environment. This study examined temporal fluctuations (monthly time scale) in antibiotic sources (ambulatory sales and data from a hospital dispensary) for Lausanne, Switzerland. Source variability (i.e., antibiotic consumption, monthly data for 2006–2010) were examined in detail for nine antibiotics – azithromycin, ciprofloxacin, clarithromycin, clindamycin, metronidazole, norfloxacin, ofloxacin, sulfamethoxazole and trimethoprim, from which two main conclusions were reached. First, some substances – azithromycin, clarithromycin, ciprofloxacin – displayed high seasonality in their consumption, with the winter peak being up to three times higher than the summer minimum. This seasonality in consumption resulted in seasonality in Predicted Environmental Concentrations (PECs). In addition, the seasonality in PECs was also influenced by that in the base wastewater flow. Second, the contribution of hospitals to the total load of antibiotics reaching the Lausanne Wastewater Treatment Plant (WTP) fluctuated markedly on a monthly time scale, but with no seasonal pattern detected. That is, there was no connection between fluctuations in ambulatory and hospital consumption for the substances investigated.

Dynamics of active pharmaceutical ingredients loads in a Swiss university hospital wastewaters and prediction of the related environmental risk for the aquatic ecosystems.

The wastewater contamination of a Swiss university hospital by active pharmaceutical ingredient (API) residues was evaluated with a three months monitoring campaign at the outlet of the main building. Flow-proportional samples were collected with an automatic refrigerated sampler and analyzed for 15 API, including antibiotics, analgesics, antiepileptic and anti-inflammatory drugs, by using a validated LC-MS/MS method. The metals Gd and Pt were also analyzed using ICP-MS. Measured concentrations were compared to the predicted ones calculated after the drug average consumption data obtained from the hospital pharmacy. The hospital contribution to the total urban load was calculated according to the consumption data obtained from city pharmacies. Lastly, the environmental hazard and risk quotients (RQ) related to the hospital fraction and the total urban consumption were calculated. Median concentrations of the 15 selected compounds were ranging from 0.04 to 675 μg/L, with a mean detection frequency of 84%. The ratio between predicted and measured environmental concentrations (PEC/MEC) has shown a good accuracy for 5 out of 15 compounds, revealing over- and under-estimations of the PEC model. Mean daily loads were ranging between 0.01 and 14.2g/d, with the exception of paracetamol (109.7 g/d). The hospital contribution to the total urban loads varied from 2.1 to 100% according to the compound. While taking into account dilution and removal efficiencies in wastewater treatment plant, only the hospital fraction of the antibiotics ciprofloxacin and sulfamethoxazole showed, respectively, a high (RQ>1) and moderate (RQ>0.1) risk for the aquatic ecosystems. Nevertheless, when considering the total urban consumption, 7 compounds showed potential deleterious effects on aquatic organisms (RQ>1): gabapentin, sulfamethoxazole, ciprofloxacin, piperacillin, ibuprofen, diclofenac and mefenamic acid. In order to reduce inputs of API residues originating from hospitals various solutions can be envisioned. With results of the present study, hospital managers can start handling this important issue.