Is throat screening necessary to detect methicillin-resistant Staphylococcus aureus colonization in patients upon admission to an intensive care unit?
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Carrier State↗
Biomedical subjects
Stephan Harbarth
Publications and source records attributed to Stephan Harbarth.
Does antibiotic selection impact patient outcome?
Inadequate antibiotic therapy, generally defined as microbiologically ineffective anti-infective therapy against the causative pathogen, can influence patient outcome. However, the detrimental effects of inadequate antibiotic therapy seem to become weaker in the most severely ill patients with short life expectancies. In addition to severity of illness, other methodological issues should be carefully examined in studies assessing the excess mortality due to inadequate therapy. To adjust for confounding as much as possible in order to obtain an unbiased estimate of the magnitude of the effect of inadequate therapy is a key methodological challenge for future research. With regard to the choice of antibiotic agents, beta-lactam and aminoglycoside combination therapy does not seem to improve clinical outcome in most cases of sepsis caused by gram-negative bacteria, including Pseudomonas aeruginosa bacteremia. A potential benefit of combination therapy in the treatment of severe pneumococcal sepsis has been suggested in several observational studies, but recently published data have disputed this hypothesis. Finally, better risk scores and laboratory tools are urgently needed to improve the adequacy of empirical antibiotic therapy and patient outcomes.
Aminoglycosides↗
Effect of individual- and group-level antibiotic exposure on MRSA isolation: a multilevel analysis.
OBJECTIVES: To observe the relative role of individual and group-level antimicrobial selective pressure on subsequent methicillin-resistant Staphylococcus aureus (MRSA) isolation in a university hospital. METHODS: For this purpose, 18 596 patients were included in a retrospective statistical analysis, applying multilevel modelling with discrete time intervals at the lowest level. Individual-level and hospital group variables on antimicrobial exposure and MRSA colonization pressure were collected from computerized databases. RESULTS: The simultaneous hospital group- and individual-level analysis showed individual exposure to fluoroquinolones and collective exposure to penicillins to be associated with MRSA isolation after adjustment for colonization pressure and other potential confounders. CONCLUSIONS: These results support efforts to reduce prescriptions of selected antimicrobial drug classes such as fluoroquinolones and show the added value of multilevel analysis for research on the adverse outcomes of antibiotic prescribing.
Aged↗
Pro-adrenomedullin to predict severity and outcome in community-acquired pneumonia [ISRCTN04176397].
INTRODUCTION: Pro-adrenomedullin (proADM) is helpful for individual risk assessment and outcome prediction in sepsis. A major cause of sepsis is community-acquired pneumonia (CAP). The aim of this study was to investigate the value of proADM levels for severity assessment and outcome prediction in CAP. METHODS: Data from 302 patients admitted to the emergency department with CAP were included in a prospective observational study. Procalcitonin, C-reactive protein levels, leukocyte count, clinical variables and the pneumonia severity index (PSI) were measured. ProADM levels were measured with a new sandwich immunoassay for mid regional ProADM (MR-proADM, Brahms AG, Hennigsdorf/Berlin, Germany). RESULTS: ProADM levels, in contrast to C-reactive protein and leukocyte count, increased with increasing severity of CAP, classified according to the PSI score (ANOVA, p < 0.001). In patients who died during follow-up, proADM levels on admission were significantly higher compared to levels in survivors (2.1 (1.5 to 3.0) versus 1.0 (0.6 to 1.6) nmol/l, p < 0.001). In a receiver operating characteristic (ROC) analysis for survival, the area under the ROC curve (AUC) for proADM was 0.76 (95% confidence interval (CI) 0.71-0.81), which was significantly higher compared to procalcitonin (p = 0.004), C-reactive protein (p < 0.001) and total leukocyte count (p = 0.001) and similar to the AUC of the PSI (0.73, p = 0.54). A clinical model including the PSI and proADM increased the prognostic accuracy to predict failure compared to a model relying on the PSI alone (AUC, 0.77 (0.70 to 0.84), p = 0.03). CONCLUSION: ProADM, as a novel biomarker, is a useful tool for the risk stratification of patients with CAP.
Adrenomedullin↗
Navigating the World Wide Web in search of resources on antimicrobial resistance.
This overview gives information on navigating for English-language Web sites on antimicrobial resistance. Web sites were gathered on the basis of personal files, articles, and an exhaustive Web search of cross-links from other Web pages. The Web sites were categorized according to users' needs into 5 broad categories, as follows: comprehensive Web sites, with information on all aspects of antimicrobial resistance-related issues; Web sites with patient information about antimicrobial resistance and about methicillin-resistant Staphylococcus aureus, in particular; Web sites covering current multinational surveillance programs; Web sites on prevention of antimicrobial resistance in health care facilities; and Web sites on control of antimicrobial resistance in the community. We compiled a selection of Web sites that seemed to be useful as starting points for physicians, epidemiologists, researchers, or patients interested in this topic.
Drug Information Services↗
Procalcitonin guidance of antibiotic therapy in community-acquired pneumonia: a randomized trial.
RATIONALE: In patients with community-acquired pneumonia, guidelines recommend antibiotic treatment for 7 to 21 d. Procalcitonin is elevated in bacterial infections, and its dynamics have prognostic implications. OBJECTIVE: To assess procalcitonin guidance for the initiation and duration of antibiotic therapy in community-acquired pneumonia. METHODS: In a randomized intervention trial, 302 consecutive patients with suspected community-acquired pneumonia were included. Data were assessed at baseline, after 4, 6, and 8 d, and after 6 wk. The control group (n = 151) received antibiotics according to usual practice. In the procalcitonin group (n = 151), antibiotic treatment was based on serum procalcitonin concentrations as follows: strongly discouraged, less than 0.1 microg/L; discouraged, less than 0.25 microg/L; encouraged, greater than 0.25 microg/L; strongly encouraged, greater than 0.5 microg/L. The primary endpoint was antibiotic use; secondary endpoints were measures of clinical, laboratory, and radiographic outcome. RESULTS: At baseline, both groups were similar regarding clinical, laboratory, and microbiology characteristics, and Pneumonia Severity Index. Procalcitonin guidance reduced total antibiotic exposure (relative risk, 0.52; 95% confidence interval, 0.48-0.55; p < 0.001), antibiotic prescriptions on admission (85 vs. 99%; p < 0.001), and antibiotic treatment duration (median, 5 vs. 12 d; p < 0.001) compared with patients treated according to guidelines. After adjustment for Pneumonia Severity Index, the hazard ratio of antibiotic discontinuation was higher in the procalcitonin group than in the control group (3.2; 95% confidence interval, 2.5 to 4.2). Outcome was similar in both groups, with an overall success rate of 83%. CONCLUSIONS: Procalcitonin guidance substantially reduces antibiotic use in community-acquired pneumonia. These findings may have important clinical and public health implications.
Aged↗
Evaluating the probability of previously unknown carriage of MRSA at hospital admission.
PURPOSE: We determined the prevalence and risk profile of patients with previously unknown carriage of methicillin-resistant Staphylococcus aureus (MRSA) at hospital admission. SUBJECTS AND METHODS: We conducted a 7-month, prospective case-controlled study in adult inpatients admitted to a university hospital with endemic MRSA. Multivariate conditional logistic regression for data sets matched 1:4 was performed to identify the risk profile of newly identified MRSA carriers. RESULTS: Overall, 399 of 12072 screened admissions (prevalence, 3.3%) were found colonized (n = 368, 92%) or infected (n = 31, 8%) with MRSA. In 204 cases (prevalence, 1.7%), MRSA carriage was newly identified. Without screening on admission, 49% (196/399) of MRSA carriers would have been missed. We identified nine independent risk factors for newly identified MRSA carriage at admission (adjusted odds ratio): male sex (1.9); age greater than 75 years (2.0); receipt of fluoroquinolones (2.7), cephalosporins (2.1), and carbapenems (3.2) in the last 6 months; previous hospitalization (1.9) or intravenous therapy (1.7) during the last 12 months; urinary catheter at admission (2.0); and intrahospital transfer (2.4). A risk score (range, 0-13) was calculated by adding points assigned to these variables. On the basis of analysis of 1006 patients included in the case-controlled study, the probability of MRSA carriage was 8% (28/342) in patients with a low score (< or =1), 19% (92/482) in patients with an intermediate score (2-4), and 46% (84/182) in patients with a high score (> or =5). The risk score had good discrimination (c-statistic, 0.73) and showed excellent calibration (P = .88). CONCLUSIONS: On-admission prevalence of previously unknown MRSA carriers was high. Applying the risk score to newly admitted patients with an intermediate or high probability of MRSA carriage could allow a more effective MRSA control strategy.
Aged↗
Genotypic and phenotypic analysis of Clostridium difficile correlated with previous antibiotic exposure.
To analyze Clostridium difficile susceptibility results and genotypes in relation to antibiotic exposures that precipitated C. difficile-associated diarrhea (CDAD), we examined 83 nosocomial C. difficile isolates recovered at a tertiary care center in Boston, Massachusetts. MICs were determined by E-test methodology using modified Brucella agar. Isolates were genotyped by pulsed-field gel electrophoresis and restriction enzyme analysis. Antibiotic susceptibilities were: ciprofloxacin (0%), clindamycin (59%), trovafloxacin (63%), ceftriaxone (73%), piperacillin/tazobactam (100%), metronidazole (100%), and vancomycin (100%). The two most common strain groups, isolated from a total of 33 patients, were much more likely to be resistant to clindamycin, erythromycin, and trovafloxacin than other strain groups [79% (26 of 33) versus 2% (1 of 50), respectively]. Clindamycin exposure was strongly associated with CDAD caused by isolates that exhibited multiple resistance to clindamycin, erythromycin, and trovafloxacin (prevalence odds ratio, 4.2; 95% confidence interval, 1.1-16.8), whereas other antimicrobials did not yield significant associations. Resistance of specific C. difficile strains to clindamycin and other antimicrobial agents may contribute to their hospital dissemination and explain, in part, the propensity of clindamycin to trigger nosocomial outbreaks.
Adult↗
Use of oligoarrays for characterization of community-onset methicillin-resistant Staphylococcus aureus.
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.
Adult↗
Rapid Staphylococcus aureus agr type determination by a novel multiplex real-time quantitative PCR assay.
The accessory gene regulator (agr) is a crucial regulatory component of Staphylococcus aureus involved in the control of bacterial virulence factor expression. We developed a real-time multiplex quantitative PCR assay for the rapid determination of S. aureus agr type. This assay represents a rapid and affordable alternative to sequence-based strategies for assessing relevant epidemiological information.
Bacterial Proteins↗
Evaluation of rapid screening and pre-emptive contact isolation for detecting and controlling methicillin-resistant Staphylococcus aureus in critical care: an interventional cohort study.
INTRODUCTION: Rapid 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. METHOD: Since 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. RESULTS: During 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). CONCLUSION: The 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.
Cohort Studies↗
Mid-regional pro-adrenomedullin as a prognostic marker in sepsis: an observational study.
INTRODUCTION: Measurement of biomarkers is a potential approach to early assessment and prediction of mortality in patients with sepsis. The aim of the present study was to evaluate the prognostic value of mid-regional pro-adrenomedullin (MR-proADM) levels in a cohort of medical intensive care patients and to compare it with other biomarkers and physiological scores. METHOD: We evaluated blood samples from 101 consecutive critically ill patients admitted to the intensive care unit and from 160 age-matched healthy control individuals. The patients had initially been enrolled in a prospective observational study investigating the prognostic value of endocrine dysfunction in critically ill patients ("PEDCRIP" Study). The prognostic value of MR-proADM levels was compared with those of two physiological scores and of various biomarkers (for example C-reactive Protein, IL-6, procalcitonin). MR-proADM was measured in EDTA plasma from all patients using a new sandwich immunoassay. RESULTS: On admission, 53 patients had sepsis, severe sepsis, or septic shock, and 48 had systemic inflammatory response syndrome. Median MR-proADM levels on admission (nmol/l [range]) were 1.1 (0.3-3.7) in patients with systemic inflammatory response syndrome, 1.8 (0.4-5.8) in those with sepsis, 2.3 (1.0-17.6) in those with severe sepsis and 4.5 (0.9-21) in patients with septic shock. In healthy control individuals the median MR-proADM was 0.4 (0.21-0.97). On admission, circulating MR-proADM levels in patients with sepsis, severe sepsis, or septic shock were significantly higher in nonsurvivors (8.5 [0.8-21.0]; P < 0.001) than in survivors (1.7 [0.4-17.6]). In a receiver operating curve analysis of survival of patients with sepsis, the area under the curve (AUC) for MR-proADM was 0.81, which was similar to the AUCs for IL-6, Acute Physiology and Chronic Health Evaluation II score and Simplified Acute Physiology Score II. The prognostic value of MR-proADM was independent of the sepsis classification system used. CONCLUSION: MR-proADM may be helpful in individual risk assessment in septic patients.
APACHE↗
Prevalence and prediction of previously unknown MRSA carriage on admission to a geriatric hospital.
OBJECTIVES: to determine the prevalence and characteristics of previously unknown methicillin-resistant Staphylococcus aureus (MRSA) carriers at admission. DESIGN: two prospective case-control studies. SUBJECTS: 1,621 elderly patients were screened for MRSA carriage within 24 hours after admission to a geriatric hospital in Geneva, Switzerland. METHODS: risk factors associated with previously unknown MRSA carriage were determined in the derivation group, and the resulting risk score was evaluated in the validation cohort using logistic regression analysis. RESULTS: prevalence of MRSA carriage at admission increased from 7.3% (53/724 patients) in 2001 to 8.7% (78/897 patients) in 2003, with a corresponding prevalence of unknown MRSA carriers of 4.6 and 5.8%, respectively. Three variables were independently associated with previously unknown MRSA carriage: recent antibiotic treatment (adjusted OR (aOR) 2.3; 95% CI 1.0-5.1), intra-hospital transfer (aOR 2.5; 95% CI 1.2-5.3), and hospitalization in the past 2 years (aOR 2.7; 95% CI 1.1-6.7). In the validation cohort, the probability of MRSA carriage increased across risk scores: 0 point, 4% prevalence (6/146); 1 point, 15% (21/136); and $2 points, 31% (21/68; P<0.001). The risk score showed good discrimination and calibration in both groups. CONCLUSIONS: our risk score, which used a simple additive point system to estimate the likelihood of unknown MRSA carriage, had good accuracy and generalised well in an independent sample of patients. Once validated in a clinical trial, our risk score may be used as a tool to optimise MRSA control.
Aged, 80 and over↗
Long-term reduction of vascular access-associated bloodstream infection.
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Catheterization, Central Venous↗
Meticillin-resistant Staphylococcus aureus.
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Europe↗
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.
Aged↗
Use of an automated multiple-locus, variable-number tandem repeat-based method for rapid and high-throughput genotyping of Staphylococcus aureus isolates.
Fast and reliable genotyping methods that allow real-time epidemiological surveillance would be instrumental to monitoring of the spread of methicillin-resistant Staphylococcus aureus. We describe an automated variable-number tandem repeat-based method for the rapid genotyping of Staphylococcus aureus. Multiplex PCR amplifications with eight primer pairs that target gene regions with variable numbers of tandem repeats were resolved by microcapillary electrophoresis and automatically assessed by cluster analysis. This genotyping technique was evaluated for its discriminatory power and reproducibility with clinical isolates of various origins, including a panel of control strains previously characterized by several typing methods and collections from either long-term carriers or defined nosocomial outbreaks. All steps of this new procedure were developed to ensure a rapid turnaround time and moderate cost. The results obtained suggest that this rapid approach is a valuable tool for the genotyping of S. aureus isolates in real time.
Automation↗
Community-associated methicillin-resistant Staphylococcus aureus, Switzerland.
Two case-control studies evaluated the prevalence of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) carriage at hospital admission and characteristics of patients with CA-MRSA. Among 14,253 patients, CA-MRSA prevalence was 0.9/1,000 admissions. Although 5 CA-MRSA isolates contained Panton-Valentine leukocidin, only 1 patient had a previous skin infection. No easily modifiable risk factor for CA-MRSA was identified.
Adult↗