J. Kristie Johnson

Comparative effectiveness of nafcillin or cefazolin versus vancomycin in methicillin-susceptible Staphylococcus aureus bacteremia

BackgroundThe high prevalence of methicillin-resistant S. aureus (MRSA) has led clinicians to select antibiotics that have coverage against MRSA, usually vancomycin, for empiric therapy for suspected staphylococcal infections. Clinicians often continue vancomycin started empirically even when methicillin-susceptible S. aureus (MSSA) strains are identified by culture. However, vancomycin has been associated with poor outcomes such as nephrotoxicity, persistent bacteremia and treatment failure. The objective of this study was to compare the effectiveness of vancomycin versus the beta-lactam antibiotics nafcillin and cefazolin among patients with MSSA bacteremia. The outcome of interest for this study was 30-day in-hospital mortality.MethodsThis retrospective cohort study included all adult in-patients admitted to a tertiary-care facility between January 1, 2003 and June 30, 2007 who had a positive blood culture for MSSA and received nafcillin, cefazolin or vancomycin. Cox proportional hazard models were used to assess independent mortality hazards comparing nafcillin or cefazolin versus vancomycin. Similar methods were used to estimate the survival benefits of switching from vancomycin to nafcillin or cefazolin versus leaving patients on vancomycin. Each model included statistical adjustment using propensity scores which contained variables associated with an increased propensity to receive vancomycin.Results267 patients were included; 14% (38/267) received nafcillin or cefazolin, 51% (135/267) received both vancomycin and either nafcillin or cefazolin, and 35% (94/267) received vancomycin. Thirty (11%) died within 30 days. Those receiving nafcillin or cefazolin had 79% lower mortality hazards compared with those who received vancomycin alone (adjusted hazard ratio (HR): 0.21; 95% confidence interval (CI): 0.09, 0.47). Among the 122 patients who initially received vancomycin empirically, those who were switched to nafcillin or cefazolin (66/122) had 69% lower mortality hazards (adjusted HR: 0.31; 95% CI: 0.10, 0.95) compared to those who remained on vancomycin.ConclusionsReceipt of nafcillin or cefazolin was protective against mortality compared to vancomycin even when therapy was altered after culture results identified MSSA. Convenience of vancomycin dosing may not outweigh the potential benefits of nafcillin or cefazolin in the treatment of MSSA bacteremia.

Emergence of Klebsiella pneumoniae carbapenemase-producing bacteria.

Klebsiella pneumoniae carbapenemase (KPC)-producing bacteria are a group of emerging highly drug-resistant Gram-negative bacilli causing infections associated with significant morbidity and mortality. Once confined to outbreaks in the northeastern United States (US), they have spread throughout the US and most of the world. KPCs are an important mechanism of resistance for an increasingly wide range of Gram-negative bacteria and are no longer limited to K pneumoniae. KPC-producing bacteria are often misidentified by routine microbiological susceptibility testing and incorrectly reported as sensitive to carbapenems; however, resistance to the carbapenem antibiotic ertapenem is common and a better indicator of the presence of KPCs. Carbapenem antibiotics are generally not effective against KPC-producing organisms. The best therapeutic approach to KPC-producing organisms has yet to be defined; however, common treatments based on in vitro susceptibility testing are the polymyxins, tigecycline, and less frequently, aminoglycoside antibiotics. The purpose of this review is to identify the various challenges that KPC-producing bacteria present to clinicians. These include the need for special techniques for microbiological detection, the potential for nosocomial transmission, and therapeutic challenges related to limited, relatively unproven antimicrobial treatment options.

Frequent Multidrug-Resistant Acinetobacter baumannii Contamination of Gloves, Gowns, and Hands of Healthcare Workers

BACKGROUND Multidrug-resistant (MDR) gram-negative bacilli are important nosocomial pathogens. OBJECTIVE To determine the incidence of transmission of MDR Acinetobacter baumannii and Pseudomonas aeruginosa from patients to healthcare workers (HCWs) during routine patient care. DESIGN Prospective cohort study. SETTING Medical and surgical intensive care units. Methods. We observed HCWs who entered the rooms of patients colonized with MDR A. baumannii or colonized with both MDR A. baumannii and MDR P. aeruginosa. We examined their hands before room entry, their disposable gloves and/or gowns upon completion of patient care, and their hands after removal of gloves and/or gowns and before hand hygiene. RESULTS Sixty-five interactions occurred with patients colonized with MDR A. baumannii and 134 with patients colonized with both MDR A. baumannii and MDR P. aeruginosa. Of 199 interactions between HCWs and patients colonized with MDR A. baumannii, 77 (38.7% [95% confidence interval {CI}, 31.9%-45.5%]) resulted in HCW contamination of gloves and/or gowns, and 9 (4.5% [95% CI, 1.6%-7.4%]) resulted in contamination of HCW hands after glove removal before hand hygiene. Of 134 interactions with patients colonized with MDR P. aeruginosa, 11 (8.2% [95% CI, 3.6%-12.9%]) resulted in HCW contamination of gloves and/or gowns, and 1 resulted in HCW contamination of hands. Independent risk factors for contamination with MDR A. baumannii were manipulation of wound dressing (adjusted odds ratio [aOR], 25.9 [95% CI, 3.1-208.8]), manipulation of artificial airway (aOR, 2.1 [95% CI, 1.1-4.0]), time in room longer than 5 minutes (aOR, 4.3 [95% CI, 2.0-9.1]), being a physician or nurse practitioner (aOR, 7.4 [95% CI, 1.6-35.2]), and being a nurse (aOR, 2.3 [95% CI, 1.1-4.8]). CONCLUSIONS Gowns, gloves, and unwashed hands of HCWs were frequently contaminated with MDR A. baumannii. MDR A. baumannii appears to be more easily transmitted than MDR P. aeruginosa and perhaps more easily transmitted than previously studied methicillin-resistant Staphylococcus aureus or vancomycin-resistant Enterococcus. This ease of transmission may help explain the emergence of MDR A. baumannii.

Transfer of multidrug-resistant bacteria to healthcare workers' gloves and gowns after patient contact increases with environmental contamination.

Objective:To assess the role of environmental contamination in the transmission of multidrug-resistant bacteria to healthcare workers’ clothing. Design:Prospective cohort. Setting:Six intensive care units at a tertiary care hospital. Subjects:Healthcare workers including registered nurses, patient care technicians, respiratory therapists, occupational/physical therapists, and physicians. Interventions:None. Measurements and Main Results:One hundred twenty of 585 (20.5%) healthcare worker/patient interactions resulted in contamination of healthcare workers’ gloves or gowns. Multidrug-resistant Acinetobacter baumannii contamination occurred most frequently, 55 of 167 observations (32.9%; 95% confidence interval [CI] 25.8% to 40.0%), followed by multidrug-resistant Pseudomonas aeruginosa, 15 of 86 (17.4%; 95% CI 9.4% to 25.4%), vancomycin-resistant Enterococcus, 25 of 180 (13.9%, 95% CI 8.9, 18.9%) and methicillin-resistant Staphylococcus aureus, 21 of 152 (13.8%; 95% CI 8.3% to 19.2%). Independent risk factors associated with healthcare worker contamination with multidrug-resistant bacteria were positive environmental cultures (odds ratio [OR] 4.2; 95% CI 2.7–6.5), duration in room for >5 mins (OR 2.0; 95% CI 1.2–3.4), performing physical examinations (OR 1.7; 95% CI 1.1–2.8), and contact with the ventilator (OR 1.8; 95% CI, 1.1–2.8). Pulsed field gel electrophoresis determined that 91% of healthcare worker isolates were related to an environmental or patient isolate. Conclusions:The contamination of healthcare workers’ protective clothing during routine care of patients with multidrug-resistant organisms is most frequent with A. baumannii. Environmental contamination was the major determinant of transmission to healthcare workers’ gloves or gowns. Compliance with contact precautions and more aggressive environmental cleaning may decrease transmission.

Increased Mortality with Accessory Gene Regulator (agr) Dysfunction in Staphylococcus aureus among Bacteremic Patients

ABSTRACT Accessory gene regulator (agr) dysfunction in Staphylococcus aureus has been associated with a longer duration of bacteremia. We aimed to assess the independent association between agr dysfunction in S. aureus bacteremia and 30-day in-hospital mortality. This retrospective cohort study included all adult inpatients with S. aureus bacteremia admitted between 1 January 2003 and 30 June 2007. Severity of illness prior to culture collection was measured using the modified acute physiology score (APS). agr dysfunction in S. aureus was identified semiquantitatively by using a δ-hemolysin production assay. Cox proportional hazard models were used to measure the association between agr dysfunction and 30-day in-hospital mortality, statistically adjusting for patient and pathogen characteristics. Among 814 patient admissions complicated by S. aureus bacteremia, 181 (22%) patients were infected with S. aureus isolates with agr dysfunction. Overall, 18% of patients with agr dysfunction in S. aureus died, compared to 12% of those with functional agr in S. aureus (P = 0.03). There was a trend toward higher mortality among patients with S. aureus with agr dysfunction (adjusted hazard ratio [HR], 1.34; 95% confidence interval [CI], 0.87 to 2.06). Among patients with the highest APS (scores of >28), agr dysfunction in S. aureus was significantly associated with mortality (adjusted HR, 1.82; 95% CI, 1.03 to 3.21). This is the first study to demonstrate an independent association between agr dysfunction and mortality among severely ill patients. The δ-hemolysin assay examining agr function may be a simple and inexpensive approach to predicting patient outcomes and potentially optimizing antibiotic therapy.

Lower Antibody Levels to Staphylococcus aureus Exotoxins Are Associated With Sepsis in Hospitalized Adults With Invasive S. aureus Infections

BACKGROUND Staphylococcus aureus has numerous virulence factors, including exotoxins that may increase the severity of infection. This study was aimed at assessing whether preexisting antibodies to S. aureus toxins are associated with a lower risk of sepsis in adults with S. aureus infection complicated by bacteremia. METHODS We prospectively identified adults with S. aureus infection from 4 hospitals in Baltimore, MD, in 2009–2011. We obtained serum samples from prior to or at presentation of S. aureus bacteremia to measure total immunoglobulin G (IgG) and IgG antibody levels to 11 S. aureus exotoxins. Bacterial isolates were tested for the genes encoding S. aureus exotoxins using polymerase chain reaction (PCR). RESULTS One hundred eligible subjects were included and 27 of them developed sepsis. When adjusted for total IgG levels and stratified for the presence of toxin in the infecting isolate as appropriate, the risk of sepsis was significantly lower in those patients with higher levels of IgG against α-hemolysin (Hla), δ-hemolysin (Hld), Panton Valentine leukocidin (PVL), staphylococcal enterotoxin C-1 (SEC-1), and phenol-soluble modulin α3 (PSM-α3). CONCLUSIONS Our results suggest that higher antibody levels against Hla, Hld, PVL, SEC-1, and PSM-α3 may protect against sepsis in patients with invasive S. aureus infections.

Multicenter Evaluation of BioFire FilmArray Meningitis/Encephalitis Panel for Detection of Bacteria, Viruses, and Yeast in Cerebrospinal Fluid Specimens

ABSTRACT Rapid diagnosis and treatment of infectious meningitis and encephalitis are critical to minimize morbidity and mortality. Comprehensive testing of cerebrospinal fluid (CSF) often includes Gram stain, culture, antigen detection, and molecular methods, paired with chemical and cellular analyses. These methods may lack sensitivity or specificity, can take several days, and require significant volume for complete analysis. The FilmArray Meningitis/Encephalitis (ME) Panel is a multiplexed in vitro diagnostic test for the simultaneous, rapid (∼1-h) detection of 14 pathogens directly from CSF specimens: Escherichia coli K1, Haemophilus influenzae, Listeria monocytogenes, Neisseria meningitidis, Streptococcus pneumoniae, Streptococcus agalactiae, cytomegalovirus, enterovirus, herpes simplex virus 1 and 2, human herpesvirus 6, human parechovirus, varicella-zoster virus, and Cryptococcus neoformans/Cryptococcus gattii. We describe a multicenter evaluation of 1,560 prospectively collected CSF specimens with performance compared to culture (bacterial analytes) and PCR (all other analytes). The FilmArray ME Panel demonstrated a sensitivity or positive percentage of agreement of 100% for 9 of 14 analytes. Enterovirus and human herpesvirus type 6 had agreements of 95.7% and 85.7%, and L. monocytogenes and N. meningitidis were not observed in the study. For S. agalactiae, there was a single false-positive and false-negative result each, for a sensitivity and specificity of 0 and 99.9%, respectively. The specificity or negative percentage of agreement was 99.2% or greater for all other analytes. The FilmArray ME Panel is a sensitive and specific test to aid in diagnosis of ME. With use of this comprehensive and rapid test, improved patient outcomes and antimicrobial stewardship are anticipated.

Systematic Review of Measurement and Adjustment for Colonization Pressure in Studies of Methicillin-Resistant Staphylococcus aureus, Vancomycin-Resistant Enterococci, and Clostridium difficile Acquisition

OBJECTIVE Colonization pressure is an important infection control metric. The aim of this study was to describe the definition and measurement of and adjustment for colonization pressure in nosocomial-acquisition risk factor studies of methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), and Clostridium difficile. METHODS We performed a computerized search of studies of nosocomial MRSA, VRE, and C. difficile acquisition published before July 1, 2009, through MEDLINE. Studies were included if a study outcome was MRSA, VRE, or C. difficile acquisition; the authors identified risk factors associated with MRSA, VRE, or C. difficile acquisition; and the study measured colonization pressure. RESULTS The initial MEDLINE search yielded 505 articles. Sixty-six of these were identified as studies of nosocomial MRSA, VRE, or C. difficile acquisition; of these, 18 (27%) measured colonization pressure and were included in the final review. The definition of colonization pressure varied considerably between studies: the proportion of MRSA- or VRE-positive patients (5 studies), the proportion of MRSA- or VRE-positive patient-days (6 studies), or the total or mean number of MRSA-, VRE-, or C. difficile-positive patients or patient-days (7 studies) in the unit over periods of varying length. In 10 of 13 studies, colonization pressure was independently associated with MRSA, VRE, or C. difficile acquisition. CONCLUSION There is a need for a simple and consistent method to quantify colonization pressure in both research and routine clinical care to accurately assess the effect of colonization pressure on cross-transmission of antibiotic-resistant bacteria.

Genomic comparison of multi-drug resistant invasive and colonizing Acinetobacter baumannii isolated from diverse human body sites reveals genomic plasticity.

BackgroundAcinetobacter baumannii has recently emerged as a significant global pathogen, with a surprisingly rapid acquisition of antibiotic resistance and spread within hospitals and health care institutions. This study examines the genomic content of three A. baumannii strains isolated from distinct body sites. Isolates from blood, peri-anal, and wound sources were examined in an attempt to identify genetic features that could be correlated to each isolation source.ResultsPulsed-field gel electrophoresis, multi-locus sequence typing and antibiotic resistance profiles demonstrated genotypic and phenotypic variation. Each isolate was sequenced to high-quality draft status, which allowed for comparative genomic analyses with existing A. baumannii genomes. A high resolution, whole genome alignment method detailed the phylogenetic relationships of sequenced A. baumannii and found no correlation between phylogeny and body site of isolation. This method identified genomic regions unique to both those isolates found on the surface of the skin or in wounds, termed colonization isolates, and those identified from body fluids, termed invasive isolates; these regions may play a role in the pathogenesis and spread of this important pathogen. A PCR-based screen of 74 A. baumanii isolates demonstrated that these unique genes are not exclusive to either phenotype or isolation source; however, a conserved genomic region exclusive to all sequenced A. baumannii was identified and verified.ConclusionsThe results of the comparative genome analysis and PCR assay show that A. baumannii is a diverse and genomically variable pathogen that appears to have the potential to cause a range of human disease regardless of the isolation source.

Empiric antibiotic therapy for Staphylococcus aureus bacteremia may not reduce in-hospital mortality: a retrospective cohort study.

Background Appropriate empiric therapy, antibiotic therapy with in vitro activity to the infecting organism given prior to confirmed culture results, may improve Staphylococcus aureus outcomes. We aimed to measure the clinical impact of appropriate empiric antibiotic therapy on mortality, while statistically adjusting for comorbidities, severity of illness and presence of virulence factors in the infecting strain. Methodology We conducted a retrospective cohort study of adult patients admitted to a tertiary-care facility from January 1, 2003 to June 30, 2007, who had S. aureus bacteremia. Time to appropriate therapy was measured from blood culture collection to the receipt of antibiotics with in vitro activity to the infecting organism. Cox proportional hazard models were used to measure the association between receipt of appropriate empiric therapy and in-hospital mortality, statistically adjusting for patient and pathogen characteristics. Principal Findings Among 814 admissions, 537 (66%) received appropriate empiric therapy. Those who received appropriate empiric therapy had a higher hazard of 30-day in-hospital mortality (Hazard Ratio (HR): 1.52; 95% confidence interval (CI): 0.99, 2.34). A longer time to appropriate therapy was protective against mortality (HR: 0.79; 95% CI: 0.60, 1.03) except among the healthiest quartile of patients (HR: 1.44; 95% CI: 0.66, 3.15). Conclusions/Significance Appropriate empiric therapy was not associated with decreased mortality in patients with S. aureus bacteremia except in the least ill patients. Initial broad antibiotic selection may not be widely beneficial.