A Trial of Discontinuation of Empiric Vancomycin Therapy in Patients with Suspected Methicillin-Resistant Staphylococcus aureus Healthcare-Associated Pneumonia.

Dec 2012

Boyce JM, Pop OF, Abreu-Lanfranco O, Hung WY, Fisher A, Karjoo A, Thompson B, Protopapas Z.

Source

Hospital Epidemiology and Infection Control Program, Yale-New Haven Hospital, New Haven, CT.

Abstract

Background:

Healthcare-associated pneumonia (HCAP) guidelines recommend de-escalating initial antibiotic therapy based on results of lower respiratory tract cultures. In the absence of adequate lower respiratory cultures, physicians are sometimes reluctant to discontinue empiric vancomycin given for suspected methicillin-resistant Staphylococcus aureus (MRSA) HCAP. We evaluated a strategy of discontinuing vancomycin if both nasal and throat cultures were negative for MRSA when lower respiratory cultures were not available.Methods:An antimicrobial stewardship team identified patients receiving empiric vancomycin for suspected or proven HCAP, but for whom adequate lower respiratory cultures were not available. Nasal and throat swab specimens were obtained and plated on MRSA selective media. If both nasal and throat MRSA cultures were negative, the stewardship team recommended discontinuation of empiric vancomycin. Demographic and clinical aspects, a clinical pulmonary infection score (CPIS) on the day of the stewardship recommendation, and mortality of patients for whom vancomycin was discontinued were obtained by retrospective chart review.Results:A convenience sample of 91 patients with nasal and throat cultures negative for MRSA in the absence of adequate respiratory cultures had empiric vancomycin therapy discontinued. A retrospective review revealed that 88 (97%) of patients had a CPIS ≤ 6 on the day of the stewardship recommendation. In-hospital mortality (7.7%) was similar to a previous study of de-escalation of antibiotics in pneumonia patients without adequate cultures.

Conclusion:

In the absence of adequate lower respiratory cultures, it is reasonable to discontinue empiric vancomycin HCAP therapy in patients with negative MRSA nasal and throat cultures and CPIS.

 Antimicrobial Agents and Chemotherapy

Impact of vancomycin minimum inhibitory concentration on clinical outcomes of patients with vancomycin-susceptible Staphylococcus aureus infections: a meta-analysis and meta-regression.

Oct 2012

Mavros MN, Tansarli GS, Vardakas KZ, Rafailidis PI, Karageorgopoulos DE, Falagas ME.

Source

Alfa Institute of Biomedical Sciences (AIBS), Athens, Greece; Department of Surgery, Massachusetts General Hospital & Harvard Medical School, Boston, MA, USA.

Abstract

Although the vancomycin minimum inhibitory concentration (VMIC) susceptibility breakpoint for Staphylococcus aureus was recently lowered to ≤2mg/L, it is argued that isolates in the higher levels of the susceptible range may bear adverse clinical outcomes. Clinical outcomes (all-cause mortality and treatment failure) of patients with S. aureus infections by 'high-VMIC' (conventionally defined as VMIC >1mg/L but ≤2mg/L) and 'low-VMIC' (VMIC≤1mg/L) isolates were compared by performing a systematic review and meta-analysis. The effect of potential confounders was assessed by univariate meta-regression analyses. In total, 33 studies (6210 patients) were included. Most studies were retrospective (28/33), used the Etest (22/33) and referred to meticillin-resistant S. aureus (MRSA) infections (26/33) and bacteraemia (23/33). Irrespective of VMIC testing method, meticillin resistance and site of infection, the high-VMIC group had higher mortality [relative risk (RR)=1.21 (95% confidence interval 1.03-1.43); 4612 patients] and more treatment failures [RR=1.67 (1.26-2.21); 2049 patients] than the low-VMIC group. The results were not affected by the potential confounders and were reproduced in the subset of patients withMRSA infections [mortality, RR=1.19 (1.02-1.40), 2956 patients; treatment failure, RR=1.69 (1.26-2.25), 1793 patients]. In conclusion, infection by vancomycin-susceptible S. aureus with VMIC>1mg/L appears to be associated with higher mortality than VMIC≤1mg/L. Further research is warranted to verify these results and to assess the impact of VMIC on meticillin-susceptible S. aureus infections. Evaluation of alternative antimicrobial agents also appears justified.

Elsevier

Formal infectious diseases consultation is associated with decreased mortality in Staphylococcusaureus bacteraemia.

Mar 2012

Robinson JO, Pozzi-Langhi S, Phillips M, Pearson JC, Christiansen KJ, Coombs GW, Murray RJ.

Source

Department of Microbiology and Infectious Diseases, PathWest Laboratory Medicine Royal Perth Hospital, Wellington Street, Perth, 6000, Western Australia, Australia, owen.robinson@health.wa.gov.au.

Abstract

To determine the impact of infectious diseases consultation (IDC) in Staphylococcus aureus bacteraemia. All MRSAbacteraemia and a random subset of MSSA bacteraemia were retrospectively analysed. Out of 599 SAB episodes, 162 (27%) were followed by an IDC. Patients with IDC were younger and more frequently intravenous drug users, but fewer resided in a long-term care facility or were indigenous. Hospital length of stay was longer (29.5 vs 17 days, p < 0.001), and endocarditis (19.1% vs 7.3%, p < 0.001) and metastatic seeding (22.2% vs 10.1%, p < 0.001) were more frequent in the IDC group; however, SAPS II scores were lower in the IDC group (27 vs 37, p < 0.001). ICU admission rates in the two groups were similar. The isolate tested susceptible to empirical therapy more frequently in the IDC group (88.9% vs 78.0%, p = 0.003). Seven-day (3.1 vs 16.5%), 30-day (8.0% vs 27.0%) and 1-year mortality (22.2% vs 44.9%) were all lower in the IDC group (all p < 0.001). Multivariate analysis showed that effective initial therapy was the only variable associated with the protective effect of IDC. In patients with SAB, all-cause mortality was significantly lower in patients who had an IDC, because of the higher proportion of patients receiving effective initial antibiotics.

PubMed

Methicillin-resistant Staphylococcus aureus infection is associated with increased mortality.

Otto M.

Source

Pathogen Molecular Genetics Section, Laboratory of Human Bacterial Pathogenesis, National Institute of Allergy & Infectious Diseases, NIH, Bethesda, MD, USA. motto@niaid.nih.gov.

Abstract

Evaluation of: Hanberger H, Walther S, Leone M et al. Increased mortality associated with meticillin-resistantStaphylococcus aureus (MRSA) infection in the intensive care unit: results from the EPIC II study. Int. J. Antimicrob. Agents 38(4), 331-335 (2011). Methicillin resistance is a widespread and major source of treatment complication in Staphylococcusaureus infections. Whether infections with methicillin-resistant S. aureus are associated with a worse clinical outcome, such as higher mortality, has remained controversial. Analyzing data from a large, global multicenter study, Hanberger et al. demonstrate that methicillin-resistant S. aureus infections are associated with approximately 50% higher mortality in the intensive care unit and significantly more frequent among critically ill patients than infections with methicillin-susceptible S.aureus. These findings call for the implementation or continuation of active methicillin-resistant S. aureus surveillance measures.

PubMed

A comparison of linezolid with glycopeptides in severe MRSA pneumonia.

A comparison of linezolid with glycopeptides in severe MRSA pneumonia.

Expert Rev Anti Infect Ther. 2009 Oct

Abunasser J, Metersky ML.

Division of Pulmonary and Critical Care Medicine, University of Connecticut Health Center, Farmington, CT 06030-1225, USA. jafar_jamil@hotmail.com

Evaluation of: Luna CM, Bruno DA, García-Morato J et al. Effect of linezolid compared with glycopeptides in methicillin-resistant Staphylococcus aureus severe pneumonia in piglets. Chest 135(6), 1564-1571 (2009). Methicillin-resistant Staphylococcus aureus (MRSA) has emerged as a major pathogen in nosocomial infections and accounts for a large proportion of nosocomial pneumonia. However, there are limited antibiotics available for the treatment of this serious and potentially lethal infection. Until recently, the only effective antibiotic was vancomycin, but the oxazolidinones, such as linezolid, have been shown to be a valuable addition to the arsenal of antimicrobial agents that can be used for MRSA pneumonia.

Clinical trials have been conducted to compare vancomycin and linezolid head-to-head in pneumonia and, in post hoc subgroup analyses, showed that linezolid use was associated with improved survival. The ensuing debate over these results was dominated by two opinions; there were those who speculated on the mechanism by which linezolid achieved this benefit, namely attributing it to pharmacodynamics and pharmacokinetics, and others who criticized the methodology of the studies and questioned the validity of the results altogether.

This study by Luna and colleagues was designed with several goals in mind. The first was to attempt to generate an animal model of MRSA pneumonia in piglets by duplicating techniques used in animal models of Gram-negative pneumonia. Then they studied the effect of three antibiotics (vancomycin, linezolid and teicoplanin) on outcomes in the same model, while simultaneously measuring antibiotic levels in the serum, bronchoalveolar lavage fluid and lung tissue, in an attempt to attribute differences in survival to pharmacological properties of the drugs used.

Their results showed a survival benefit only for linezolid, despite the fact that all three antibiotics had levels above MIC in all the compartments sampled, leading them to speculate that linezolid may have improved outcomes by mechanisms not directly related to its antimicrobial actions.

Expert Reviews

Risk of Infection and Death due to Methicillin-Resistant Staphylococcus aureus in Long-term Carriers.

Risk of Infection and Death due to Methicillin-Resistant Staphylococcus aureus in Long-term Carriers.

Clin Infect Dis. 2008 Jun

Datta R, Huang SS.
1Department of Ambulatory Care and Prevention, Harvard Medical School and Harvard Pilgrim Health Care, and 2Channing Laboratory, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts; 3Division of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, Connecticut; and 4Division of Infectious Diseases, University of California Irvine School of Medicine, Irvine.

Background: Patients with newly acquired methicillin-resistant Staphylococcus aureus (MRSA) have significant risks of short-term morbidity and mortality due to this pathogen. We were interested in assessing whether long-term carriers have persistent risks of disease and whether all carriers, regardless of the duration of carriage, should be considered to be reasonable candidates for interventions to reduce the risk of infection. Methods. We conducted a single-center retrospective cohort study to evaluate the risk of subsequent MRSA infection and death among patients known to have harbored MRSA for at least 1 year (i.e., prevalent carriers).

Results: Among 281 prevalent carriers, 65 (23%) developed a total of 96 discrete and unrelated MRSA infections in the year after their identification as prevalent carriers. The most common infections were pneumonia (accounting for 39% of MRSA infections), soft-tissue infection (14%), and central venous catheter infection (14%). Twenty-four percent of all infections involved bacteremia. Thirty-eight MRSA infections occurred during a new hospitalization, and 32 (84%) of these infections were the reason for admission to the hospital. MRSA contributed to 14 deaths, with 6 of these deaths deemed to be attributable to MRSA. Harboring MRSA for less then 2 and MRSA colonization at the time of detection as a prevalent carrier were predictive of subsequent infection with MRSA.

Conclusions: Individuals who are known to have harbored MRSA for greater 1 year are at high risk for subsequent MRSA morbidity and mortality and should be considered to be targets for intervention, in addition to individuals who have newly acquired this pathogen.

PMID: 18532892 [PubMed - as supplied by publisher]

Long-term outcomes following infection with meticillin-resistant or meticillin-susceptible Staphylococcus aureus.

Long-term outcomes following infection with meticillin-resistant or meticillin-susceptible Staphylococcus aureus.
J Hosp Infect. 2008 Mar

Haessler S, Mackenzie T, Kirkland KB.
Dartmouth–Hitchcock Medical Center, Dartmouth Medical School, Lebanon, New Hampshire, USA.

Staphylococcus aureus (SA) is becoming increasingly resistant to antibiotics in hospitals and the community. Long-term outcomes following susceptible and resistant SA infection have not been studied. We performed a retrospective matched pair analysis of all patients with positive culture for meticillin-resistant SA (MRSA) or meticillin-susceptible SA (MSSA) from any site to assess the outcomes of infection. Data were collected for length of hospitalisation and in-hospital mortality, as well as longer-term outcomes including all-cause mortality, number of rehospitalisations and subsequent cultures for SA during the year following infection. Twelve months after their initial SA infection, 42% of patients were dead. There were no differences between the groups in short-term mortality, length of hospitalisation, number of subsequent hospitalisations and cultures for SA during the year following infection.

Following discharge, however, MRSA infection was associated with higher mortality than MSSA at three months (32% vs 18% P=0.02), six months (42% vs 22% P=0.002) and 12 months (51% vs 32% P=0.005). In conclusion, SA infection is associated with a high one-year all-cause mortality. Most deaths occur after discharge. The likelihood of dying during the year following infection is higher for patients with MRSA infection than for those with MSSA infection.

Elsevier