Paukner, S., Gelone, S. P., Arends, S. J. R., Flamm, R. K., Sader, H. S.

Lefamulin, the first semisynthetic pleuromutilin antibacterial for intravenous and oral treatment of community-acquired bacterial pneumonia (CABP), and comparators were evaluated for in vitro activity against a global collection of pathogens commonly causing CABP (n=8595) from the 2015–2016 SENTRY Antimicrobial Surveillance Program. Lefamulin was highly active against pathogens commonly Streptococcus pneumoniae including multidrug resistant and extensively drug resistant strains (MIC50/90 for total and resistant subsets, 0.06/0.12 μg/mL; 100% inhibited at ≤1 μg/mL), Staphylococcus aureus including MRSA (both MIC50/90, 0.06/0.12 μg/mL; 99.8% and 99.6% inhibited at ≤1 μg/mL, respectively), Haemophilus influenzae (MIC50/90, 0.5/1 μg/mL; 93.8% inhibited at ≤1 μg/mL), and Moraxella catarrhalis (MIC50/90, 0.06/0.12 μg/mL; 100% inhibited at ≤0.25 μg/mL), and its activity was unaffected by resistance to other antibacterial classes.…

Abstract Background Staphylococcus aureus is a common bacterium found in the nose and throat of healthy individuals, and presents risk factors for infection and death. We investigated environmental contamination of fitness facilities with S. aureus in order to determine molecular types and antibiotic susceptibility profiles of contaminates that may be transmitted to facility patrons. Methods Environmental swabs (n = 288) were obtained from several fitness facilities (n = 16) across Northeast Ohio including cross-fit type facilities (n = 4), traditional iron gyms (n = 4), community center-based facilities (n = 5), and hospital-associated facilities (n = 3). Samples were taken from 18 different surfaces at each facility and were processed within 24 h using typical bacteriological methods. Positive isolates were subjected to antibiotic susceptibility testing and molecular characterization (PVL and mecA PCR, and spa typing). Results The overall prevalence of S. aureus on environmental surfaces in the fitness facilities was 38.2% (110/288). The most commonly colonized surfaces were the weight ball (62.5%), cable driven curl bar, and CrossFit box (62.5%), as well as the weight plates (56.3%) and treadmill handle (50%). Interestingly, the bathroom levers and door handles were the least contaminated surfaces in both male and female restroom facilities (18.8%). Community gyms (40.0%) had the highest contamination prevalence among sampled surfaces with CrossFit (38.9%), traditional gyms (38.9%), and hospital associated (33.3%) contaminated less frequently, though the differences were not significant (p = 0.875). The top spa types found overall were t008 (12.7%), t267 (10.0%), t160, t282, t338 (all at 5.5%), t012 and t442 (4.5%), and t002 (3.6%). t008 and t002 was found in all fitness facility types accept Crossfit, with t267 (25%), t548, t377, t189 (all 10.7%) the top spa types found within crossfit. All samples were resistant to benzylpenicillin, with community centers having significantly more strains resistant to oxacillin (52.8%), erythromycin (47%), clindamycin (36%), and ciprofloxacin (19%). Overall, 36.3% of isolates were multidrug resistant. Conclusions Our pilot study indicates that all facility types were contaminated by S. aureus and MRSA, and that additional studies are needed to characterize the microbiome structure of surfaces at different fitness facility types and the patrons at these facilities.…

Hong, S. I., Lee, Y.-M., Park, K.-H., Ryu, B.-H., Hong, K.-W., Kim, S., Bae, I.-G., Cho, O.-H.

The increasing use of chlorhexidine for methicillin-resistant Staphylococcus aureus (MRSA) decolonization has raised concerns about the emergence of resistance to these agents. However, the clinical significance of MRSA positive for the qacA/B-chlorhexidine tolerance genes has not been established. We investigated the clinical features and predictive factors of MRSA bloodstream infection (BSI) isolates, caused by qacA/B-positive MRSA, from 2010 to 2016 at a tertiary hospital in South Korea. A total of 246 MRSA BSI isolates were included; 71 (28.9%) isolates carried qacA/B. The annual frequency of qacA/B-positive MRSA bacteremia did not change significantly over the study period. Patients infected with qacA/B-positive MRSA had common risk factors for healthcare-associated infections, including prior antibiotic use, central venous catheterization in situ, intensive-care-unit-acquired bacteremia, and nosocomial infection. The qacA/B-positive isolates were also associated with an increasing chlorhexidine MIC and resistance to non-β-lactam antibiotics. The qacA/B-positive isolates were more likely to belong to sequence type 5 (ST5), which is a common healthcare-associated MRSA strain in South Korea. In multivariable analyses, qacA/B-positive MRSA isolates were found to be associated with agr dysfunction (aOR, 6.45; 95% CI, 2.59–16.10), ST5 MRSA strain (aOR 4.96; 95% CI, 1.85–13.26), nosocomial infection (aOR, 4.88; 95% CI, 2.20–10.83), and antibiotic use within the previous 3 months (aOR, 2.59; 95% CI, 1.20–5.59). These findings suggest that the microbiological features of qacA/B carriage may provide a selective advantage for specific MRSA strains in hospital environments.…

Kebriaei, R., Rice, S. A., Stamper, K. C., Rybak, M. J.

Glycopeptides such as vancomycin have been used as the first line therapy against MRSA infections for over half a century. Reduced susceptibility and emergence of resistance to first generation glycopeptides has led to development of second generation lipoglycopeptide derivatives such as dalbavancin which hold broader ranges of activity and enhanced pharmacokinetic properties. We evaluated the MIC values for a total of 100 isolates including 25 MRSA, 25 hVISA, 25 daptomycin non-susceptible (DNS) MRSA and 25 VISA strains against dalbavancin, ceftaroline and vancomycin alone and in combination. Dalbavancin was highly active against hVISA, DNS and MRSA strains achieving 96-100% susceptibility and 72% susceptibility against VISA strains. The combination of dalbavancin plus ceftaroline reduced dalbavancin MICs 62.5-fold and demonstrated enhanced killing against all four phenotypes in PK/PD models. Four strains of the aforementioned phenotypes were randomly chosen for pharmacodynamics/pharmacokinetic simulation models. Of interest, while both dalbavancin and vancomycin in combination with ceftaroline demonstrated significant improvement in glycopeptide fAUC/MIC values against these four phenotypes, the dalbavancin-ceftaroline combinations exhibited a 44-11270-fold higher fAUC/MIC value in comparison to vancomycin-ceftaroline combinations. In addition, the time to detection limit was reduced for this combination (24-32h) vs. the vancomycin-ceftaroline combination (24-72h). To our knowledge, this is the first comprehensive study of dalbavancin and vancomycin combinations with ceftaroline. This data provides a novel approach for combating recalcitrant MRSA infections.…

Singh, K. V., Arias, C. A., Murray, B. E.

In a mouse peritonitis model, tedizolid was comparable to linezolid and daptomycin against an Enterococcus faecium strain (VANR, AMPR), an Enterococcus faecalis strain, and an MRSA strain with and without cfr. Against a cfr(B)+ E. faecium, tedizolid was inferior in vivo to linezolid and daptomycin, despite ~ 4-fold lower MIC.…

Abstract Background Community- associated methicillin resistant Staphylococcus aureus (CA-MRSA) cause serious infections and rates continue to rise worldwide. Use of geocoded electronic health record (EHR) data to prevent spread of disease is limited in health service research. We demonstrate how geocoded EHR and spatial analyses can be used to identify risks for CA-MRSA in children, which are tied to place-based determinants and would not be uncovered using traditional EHR data analyses. Methods An epidemiology study was conducted on children from January 1, 2002 through December 31, 2010 who were treated for Staphylococcus aureus infections. A generalized estimated equations (GEE) model was developed and crude and adjusted odds ratios were based on S. aureus risks. We measured the risk of S. aureus as standardized incidence ratios (SIR) calculated within aggregated US 2010 Census tracts called spatially adaptive filters, and then created maps that differentiate the geographic patterns of antibiotic resistant and non-resistant forms of S. aureus. Results CA-MRSA rates increased at higher rates compared to non-resistant forms, p = 0.01. Children with no or public health insurance had higher odds of CA-MRSA infection. Black children were almost 1.5 times as likely as white children to have CA-MRSA infections (aOR 95% CI 1.44,1.75, p 

Galar, A., Weil, A. A., Dudzinski, D. M., Munoz, P., Siedner, M. J.

Staphylococcus aureus prosthetic valve endocarditis (PVE) remains among the most morbid bacterial infections, with mortality estimates ranging from 40% to 80%. The proportion of PVE cases due to methicillin-resistant Staphylococcus aureus (MRSA) has grown in recent decades, to account for more than 15% of cases of S. aureus PVE and 6% of all cases of PVE. Because no large studies or clinical trials for PVE have been published, most guidelines on the diagnosis and management of MRSA PVE rely upon expert opinion and data from animal models or related conditions (e.g., coagulase-negative Staphylococcus infection). We performed a review of the literature on MRSA PVE to summarize data on pathogenic mechanisms and updates in epidemiology and therapeutic management and to inform diagnostic strategies and priority areas where additional clinical and laboratory data will be particularly useful to guide therapy. Major updates discussed in this review include novel diagnostics, indications for surgical management, the utility of aminoglycosides in medical therapy, and a review of newer antistaphylococcal agents used for the management of MRSA PVE.…

Inagaki K, Lucar J, Blackshear C, et al.

AbstractBackgroundInformation on outcomes of methicillin-susceptible and -resistant S. aureus (MSSA and MRSA, respectively) bacteremia, particularly readmission is scarce, and require further research to inform optimal patient care.MethodsWe performed a retrospective analysis using the 2014 Nationwide Readmissions Database, capturing 49.3% of US hospitalizations. We identified MSSA and MRSA bacteremia using International Classification of Diseases, Ninth Revision, Clinical Modification among patients aged ≥18 years. Thirty-day readmission, mortality, length of stay and costs were assessed using Cox proportional hazards regression, logistic regression, Poisson regression, and generalized linear model with gamma distribution and log link, respectively.ResultsOf 92089 (standard error, SE: 1905) patients with S. aureus bacteremia, 48.5% (SE: 0.4%) had MRSA bacteremia. Thirty-day readmission rate was 22% (SE: 0.3) overall with no difference between MRSA and MSSA, but MRSA bacteremia had more readmission for bacteremia recurrence (hazard ratio: 1.17 [95% confidence interval, CI: 1.02-1.35]), higher in-hospital mortality (odds ratio: 1.15 [95%CI: 1.07-1.22]), and longer hospitalization (incidence rate ratio: 1.08 [95%CI: 1.06-1.11]). Readmission with bacteremia recurrence was particularly more common among patients with endocarditis, immunocompromising comorbidities, and drug abuse. The cost of readmission was $12425 (SE: 174) /case overall, and $19186 (SE: 623) in those with bacteremia recurrence.ConclusionsThirty-day readmission after S. aureus bacteremia is common and costly. MRSA bacteremia is associated with readmission for bacteremia recurrence, increased mortality, and longer hospitalization. Efforts should continue to optimize patient care, particularly for those with risk factors, to decrease readmission and associated morbidity and mortality in patients with S. aureus bacteremia.

Ki-Ho Park, Dong Youn Kim, Yu-Mi Lee, Mi Suk Lee, Kyung-Chung Kang, Jung-Hee Lee, Seong Yeon Park, Chisook Moon, Yong Pil Chong, Sung-Han Kim, Sang-Oh Lee, Sang-Ho Choi, Yang Soo Kim, Jun Hee Woo, Byung-Han Ryu, In-Gyu Bae, Oh-Hyun Cho

by Ki-Ho Park, Dong Youn Kim, Yu-Mi Lee, Mi Suk Lee, Kyung-Chung Kang, Jung-Hee Lee, Seong Yeon Park, Chisook Moon, Yong Pil Chong, Sung-Han Kim, Sang-Oh Lee, Sang-Ho Choi, Yang Soo Kim, Jun Hee Woo, Byung-Han Ryu, In-Gyu Bae, Oh-Hyun Cho Background Empiric antibiotic therapy for suspected hematogenous vertebral osteomyelitis (HVO) should be initiated immediately in seriously ill patients and may be required in those with negative microbiological results. The aim of this study was to inform the appropriate selection of empiric antibiotic regimens for the treatment of suspected HVO by analyzing antimicrobial susceptibility of isolated bacteria from microbiologically proven HVO. Method We conducted a retrospective chart review of adult patients with microbiologically proven HVO in five tertiary-care hospitals over a 7-year period. The appropriateness of empiric antibiotic regimens was assessed based on the antibiotic susceptibility profiles of isolated bacteria. Results In total, 358 cases of microbiologically proven HVO were identified. The main causative pathogens identified were methicillin-susceptible Staphylococcus aureus (33.5%), followed by methicillin-resistant S. aureus (MRSA) (24.9%), Enterobacteriaceae (19.3%), and Streptococcus species (11.7%). Extended spectrum β-lactamase (ESBL)-producing Enterobacteriaceae and anaerobes accounted for only 1.7% and 1.4%, respectively, of the causative pathogens. Overall, 73.5% of isolated pathogens were susceptible to levofloxacin plus rifampicin, 71.2% to levofloxacin plus clindamycin, and 64.5% to amoxicillin-clavulanate plus ciprofloxacin. The susceptibility to these oral combinations was lower in cases of healthcare-associated HVO (52.6%, 49.6%, and 37.6%, respectively) than in cases of community-acquired HVO (85.8%, 84.0%, and 80.4%, respectively). Vancomycin combined with ciprofloxacin, ceftriaxone, ceftazidime, or cefepime was similarly appropriate (susceptibility rates of 93.0%, 94.1%, 95.8%, and 95.8%, respectively). Conclusions Based on our susceptibility data, vancomycin combined with a broad-spectrum cephalosporin or fluoroquinolone may be appropriate for empiric treatment of HVO. Fluoroquinolone-based oral combinations may be not appropriate due to frequent resistance to these agents, especially in cases of healthcare-associated HVO.…

Petter Elstrøm, Elisabeth Astrup, Kristin Hegstad, Ørjan Samuelsen, Hege Enger, Oliver Kacelnik

by Petter Elstrøm, Elisabeth Astrup, Kristin Hegstad, Ørjan Samuelsen, Hege Enger, Oliver Kacelnik Introduction Scandinavian countries have traditionally had a low prevalence of resistant organisms, but have in recent years experienced a change in their epidemiology. We aim to describe the epidemiology of carbapenemase-producing organisms (CPOs), vancomycin-resistant enterococci (VRE) and methicillin-resistant S. aureus (MRSA) in Norway, measure the importance of infections contracted abroad, and assess the morbidity and mortality associated with these resistant bacteria in Norway. Methods and materials We used data from the Norwegian surveillance system for communicable diseases covering all findings of the selected resistant bacteria including both infections and colonisation, in the period 2006–2017. Annual trends were assessed using negative binomial regression. For MRSA, we were able to calculate the Morisita-Horn index and transmission numbers following importation in order to assess the effect this had on further domestic transmission. Results The incidence rates (per 100,000 personyears) of the three groups of resistant bacteria have increased during the period. In 2017 the incidence rates were 0.82 for CPOs, 7.09 for VRE and 43.8 for MRSA. 81% of CPO cases were diagnosed in hospitals, but 73% were infected abroad. Most VRE cases were infected in Norwegian hospitals, 85% were associated with hospitals outbreaks. MRSA was predominantly diagnosed in the community, only 21% were diagnosed in hospitals. Of all MRSA cases, 35% were infected in other countries. Most MRSA spa-types were not identified again after introduction, resulting in a transmission of MRSA equivalent to a mean of 0.30 persons infected from each spa-type identified (range: 0–22). The proportion of infections among all notified cases within each diagnose was 44% for MRSA, 9% for VRE and 45% for CPOs. Among persons notified with bacteraemia, the 30 days all-cause mortality were 20%, 16% and 50% for MRSA, VRE and CPOs respectively. Discussion The incidence rates of CPOs, VRE and MRSA in Norway are low, but increasing. The continuing increase of notified resistant bacteria highlights the need for a revision of existing infection prevention and control guidelines.…

McKinnell J, Singh R, Miller L, et al.

AbstractBackgroundMultidrug-resistant organisms (MDROs) spread between hospitals, nursing homes (NH), and long-term acute care facilities (LTACs) via patient transfers. SHIELD OC is a regional public health collaborative involving decolonization at 38 healthcare facilities selected based upon their high degree of patient sharing. We report baseline MDRO prevalence in 21 NH/LTACsMethodsA random sample of 50 adults for 21 NH/LTACs (18 NHs, 3 LTACs) were screened for methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus spp. (VRE), extended-spectrum beta-lactamase producing organisms (ESBL), and carbapenem-resistant Enterobacteriaceae (CRE) using nares, skin (axilla/groin), and peri-rectal swabs. Facility and resident characteristics associated with MDRO carriage were assessed using multivariable models clustering by person and facility.ResultsPrevalence of MDROs was 65% in NHs and 80% in LTACs. The most common MDROs in NHs were MRSA (42%) and ESBL (34%); in LTACs they were VRE (55%) and ESBL (38%). CRE prevalence was higher in facilities that manage ventilated LTAC patients and NH residents (8% vs.

Abstract Background The prognostic capability of the quick Sequential Organ Failure Assessment (qSOFA) bedside scoring tool is uncertain in non-ICU patients with sepsis due to bacteremia given the low number of patients previously evaluated. Methods We performed a retrospective cohort study of adult hospitalized patients with Staphylococcus aureus bacteremia (SAB). Medical charts were reviewed to determine qSOFA score, systemic inflammatory response syndrome (SIRS) criteria, and Pitt bacteremia score (PBS) at initial presentation; their predictive values were compared for ICU admission within 48 h, ICU stay duration > 72 h, and 30-day mortality. Results Four hundred twenty-two patients were included; 22% had qSOFA score ≥2. Overall, mean age was 56y and 75% were male. More patients with qSOFA ≥2 had altered mentation (23% vs 5%, p