Stéphan Juergen Harbarth

Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: an international expert proposal for interim standard definitions for acquired resistance

Many different definitions for multidrug-resistant (MDR), extensively drug-resistant (XDR) and pandrug-resistant (PDR) bacteria are being used in the medical literature to characterize the different patterns of resistance found in healthcare-associated, antimicrobial-resistant bacteria. A group of international experts came together through a joint initiative by the European Centre for Disease Prevention and Control (ECDC) and the Centers for Disease Control and Prevention (CDC), to create a standardized international terminology with which to describe acquired resistance profiles in Staphylococcus aureus, Enterococcus spp., Enterobacteriaceae (other than Salmonella and Shigella), Pseudomonas aeruginosa and Acinetobacter spp., all bacteria often responsible for healthcare-associated infections and prone to multidrug resistance. Epidemiologically significant antimicrobial categories were constructed for each bacterium. Lists of antimicrobial categories proposed for antimicrobial susceptibility testing were created using documents and breakpoints from the Clinical Laboratory Standards Institute (CLSI), the European Committee on Antimicrobial Susceptibility Testing (EUCAST) and the United States Food and Drug Administration (FDA). MDR was defined as acquired non-susceptibility to at least one agent in three or more antimicrobial categories, XDR was defined as non-susceptibility to at least one agent in all but two or fewer antimicrobial categories (i.e. bacterial isolates remain susceptible to only one or two categories) and PDR was defined as non-susceptibility to all agents in all antimicrobial categories. To ensure correct application of these definitions, bacterial isolates should be tested against all or nearly all of the antimicrobial agents within the antimicrobial categories and selective reporting and suppression of results should be avoided.

Effectiveness of a hospital-wide programme to improve compliance with hand hygiene

BACKGROUND Hand hygiene prevents cross infection in hospitals, but compliance with recommended instructions is commonly poor. We attempted to promote hand hygiene by implementing a hospital-wide programme, with special emphasis on bedside, alcohol-based hand disinfection. We measured nosocomial infections in parallel. METHODS We monitored the overall compliance with hand hygiene during routine patient care in a teaching hospital in Geneva, Switzerland, before and during implementation of a hand-hygiene campaign. Seven hospital-wide observational surveys were done twice yearly from December, 1994, to December, 1997. Secondary outcome measures were nosocomial infection rates, attack rates of methicillin-resistant Staphylococcus aureus (MRSA), and consumption of handrub disinfectant. FINDINGS We observed more than 20,000 opportunities for hand hygiene. Compliance improved progressively from 48% in 1994, to 66% in 1997 (p<0.001). Although recourse to handwashing with soap and water remained stable, frequency of hand disinfection substantially increased during the study period (p<0.001). This result was unchanged after adjustment for known risk factors of poor adherence. Hand hygiene improved significantly among nurses and nursing assistants, but remained poor among doctors. During the same period, overall nosocomial infection decreased (prevalence of 16.9% in 1994 to 9.9% in 1998; p=0.04), MRSA transmission rates decreased (2.16 to 0.93 episodes per 10,000 patient-days; p<0.001), and the consumption of alcohol-based handrub solution increased from 3.5 to 15.4 L per 1000 patient-days between 1993 and 1998 (p<0.001). INTERPRETATION The campaign produced a sustained improvement in compliance with hand hygiene, coinciding with a reduction of nosocomial infections and MRSA transmission. The promotion of bedside, antiseptic handrubs largely contributed to the increase in compliance.

The impact of methicillin resistance in Staphylococcus aureus bacteremia on patient outcomes: Mortality, length of stay, and hospital charges

OBJECTIVE To evaluate the impact of methicillin resistance in Staphylococcus aureus on mortality, length of hospitalization, and hospital charges. DESIGN A cohort study of patients admitted to the hospital between July 1, 1997, and June 1, 2000, who had clinically significant S. aureus bloodstream infections. SETTING A 630-bed, urban, tertiary-care teaching hospital in Boston, Massachusetts. PATIENTS Three hundred forty-eight patients with S. aureus bacteremia were studied; 96 patients had methicillin-resistant S. aureus (MRSA). Patients with methicillin-susceptible S. aureus (MSSA) and MRSA were similar regarding gender, percentage of nosocomial acquisition, length of hospitalization, ICU admission, and surgery before S. aureus bacteremia. They differed regarding age, comorbidities, and illness severity score. RESULTS Similar numbers of MRSA and MSSA patients died (22.9% vs 19.8%; P = .53). Both the median length of hospitalization after S. aureus bacteremia for patients who survived and the median hospital charges after S. aureus bacteremia were significantly increased in MRSA patients (7 vs 9 days, P = .045; 19,212 dollars vs 26,424 dollars, P = .008). After multivariable analysis, compared with MSSA bacteremia, MRSA bacteremia remained associated with increased length of hospitalization (1.29 fold; P = .016) and hospital charges (1.36 fold; P = .017). MRSA bacteremia had a median attributable length of stay of 2 days and a median attributable hospital charge of 6916 dollars. CONCLUSION Methicillin resistance in S. aureus bacteremia is associated with significant increases in length of hospitalization and hospital charges.

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.

Impact of a prevention strategy targeted at vascular-access care on incidence of infections acquired in intensive care.

BACKGROUND Intravascular devices are a leading cause of nosocomial infection. Specific prevention strategies and improved guidelines for the use of intravascular devices can decrease the rate of infection; however, the impact of a combination of these strategies on rates of vascular-access infection in intensive-care units (ICUs) is not known. We implemented a multiple-approach prevention programme to decrease the occurrence of vascular-access infection in an 18-bed medical ICU at a tertiary centre. METHODS 3154 critically ill patients, admitted between October, 1995, and November, 1997, were included in a cohort study with longitudinal assessment of an overall catheter-care policy targeted at the reduction of vascular-access infections and based on an educational campaign for vascular-access insertion and on device use and care. Incidence of ICU-acquired infections was measured by means of on-site surveillance. FINDINGS 613 infections occurred in 353 patients (19.4 infections per 100 admissions). The incidence density of exit-site catheter infection was 9.2 episodes per 1000 patient-days before the intervention, and 3.3 episodes per 1000 patient-days afterwards (relative risk 0.36 [95% CI 0.20-0.63]). Corresponding rates for bloodstream infection were 11.3 and 3.8 episodes per 1000 patient-days, respectively (0.33 [0.20-0.56]) due to decreased rates of both microbiologically documented infections and clinical sepsis. Rates of respiratory and urinary-tract infections remained unchanged, whereas those of skin or mucous-membrane infections decreased from 11.4 to 7.0 episodes per 1000 patient-days (0.62 [0.41-0.93]). Overall, the incidence of nosocomial infections decreased from 52.4 to 34.0 episodes per 1000 patient-days (0.65 [0.54-0.78]). INTERPRETATION A multiple-approach prevention strategy, targeted at the insertion and maintenance of vascular access, can decrease rates of vascular-access infections and can have a substantial impact on the overall incidence of ICU-acquired infections.

The preventable proportion of nosocomial infections: an overview of published reports

The proportion of nosocomial infections potentially preventable under routine working conditions remains unclear. We performed a systematic review to describe multi-modal intervention studies, as well as studies assessing exogenous cross-infection published during the last decade, in order to give a crude estimate of the proportion of potentially preventable nosocomial infections. The evaluation of 30 reports suggests that great potential exists to decrease nosocomial infection rates, from a minimum reduction effect of 10% to a maximum effect of 70%, depending on the setting, study design, baseline infection rates and type of infection. The most important reduction effect was identified for catheter-related bacteraemia, whereas a smaller, but still substantial potential for prevention seems to exist for other types of infections. Based on these estimates, we consider at least 20% of all nosocomial infections as probably preventable, and hope that this overview will stimulate further research on feasible and cost-effective prevention of nosocomial infections for daily practice.

Health-care workers: source, vector, or victim of MRSA?

There is ongoing controversy about the role of health-care workers in transmission of meticillin-resistant Staphylococcus aureus (MRSA). We did a search of the literature from January, 1980, to March, 2006, to determine the likelihood of MRSA colonisation and infection in health-care workers and to assess their role in MRSA transmission. In 127 investigations, the average MRSA carriage rate among 33 318 screened health-care workers was 4.6%; 5.1% had clinical infections. Risk factors included chronic skin diseases, poor hygiene practices, and having worked in countries with endemic MRSA. Both transiently and persistently colonised health-care workers were responsible for several MRSA clusters. Transmission from personnel to patients was likely in 63 (93%) of 68 studies that undertook genotyping. MRSA eradication was achieved in 449 (88%) of 510 health-care workers. Subclinical infections and colonisation of extranasal sites were associated with persistent carriage. We discuss advantages and disadvantages of screening and eradication policies for MRSA control and give recommendations for the management of colonised health-care workers in different settings.

Antibiotic selection pressure and resistance in Streptococcus pneumoniae and Streptococcus pyogenes.

We correlated outpatient antibiotic use with prevalence of penicillin-nonsusceptible Streptococcus pneumoniae (PNSP), macrolide-resistant S. pneumoniae (MRSP), and macrolide-resistant S. pyogenes (MRGAS) in 20 countries. Total antibiotic use was correlated with PNSP (r = 0.75; p < 0.001), as was macrolide use with MRSP (r = 0.88; p < 0.001) and MRGAS (r = 0.71; p = 0.004). Streptococcal resistance is directly associated with antibiotic selection pressure on a national level.

Diagnostic and prognostic accuracy of clinical and laboratory parameters in community-acquired pneumonia

BackgroundCommunity-acquired pneumonia (CAP) is the most frequent infection-related cause of death. The reference standard to diagnose CAP is a new infiltrate on chest radiograph in the presence of recently acquired respiratory signs and symptoms. This study aims to evaluate the diagnostic and prognostic accuracy of clinical signs and symptoms and laboratory biomarkers for CAP.Methods545 patients with suspected lower respiratory tract infection, admitted to the emergency department of a university hospital were included in a pre-planned post-hoc analysis of two controlled intervention trials. Baseline assessment included history, clinical examination, radiography and measurements of procalcitonin (PCT), highly sensitive C-reactive protein (hsCRP) and leukocyte count.ResultsOf the 545 patients, 373 had CAP, 132 other respiratory tract infections, and 40 other final diagnoses. The AUC of a clinical model including standard clinical signs and symptoms (i.e. fever, cough, sputum production, abnormal chest auscultation and dyspnea) to diagnose CAP was 0.79 [95% CI, 0.75–0.83]. This AUC was significantly improved by including PCT and hsCRP (0.92 [0.89–0.94]; p < 0.001). PCT had a higher diagnostic accuracy (AUC, 0.88 [0.84–0.93]) in differentiating CAP from other diagnoses, as compared to hsCRP (AUC, 0.76 [0.69–0.83]; p < 0.001) and total leukocyte count (AUC, 0.69 [0.62–0.77]; p < 0.001). To predict bacteremia, PCT had a higher AUC (0.85 [0.80–0.91]) as compared to hsCRP (p = 0.01), leukocyte count (p = 0.002) and elevated body temperature (p < 0.001). PCT, in contrast to hsCRP and leukocyte count, increased with increasing severity of CAP, as assessed by the pneumonia severity index (p < 0.001).ConclusionPCT, and to a lesser degree hsCRP, improve the accuracy of currently recommended approaches for the diagnosis of CAP, thereby complementing clinical signs and symptoms. PCT is useful in the severity assessment of CAP.

Characteristics and outcomes of public campaigns aimed at improving the use of antibiotics in outpatients in high-income countries

The worldwide increase in resistance to antimicrobial drugs has made reducing the unnecessary use of antibiotics a public health priority. There have been campaigns in many countries to educate the public about appropriate use of antibiotics in outpatients. By use of a comprehensive search strategy and structured interviews, we were able to identify and review the characteristics and outcomes of 22 campaigns done at a national or regional level in high-income countries between 1990 and 2007. The intensity of the campaigns varied widely, from simple internet to expensive mass-media campaigns. All but one campaign targeted the public and physicians simultaneously. Most campaigns that were formally evaluated seemed to reduce antibiotic use. The effect on resistance to antimicrobial drugs cannot be assessed accurately at present. Although the most effective interventions and potential adverse outcomes remain unclear, public campaigns can probably contribute to more careful use of antibiotics in outpatients, at least in high-prescribing countries.