Susan S Huang, Edward Septimus, Ken Kleinman, Julia Moody, Jason Hickok, Lauren Heim, Adrijana Gombosev, Taliser R Avery, Katherine Haffenreffer, Lauren Shimelman, Mary K Hayden, Robert A Weinstein, Caren Spencer-Smith, Rebecca E Kaganov, Michael V Murphy, Tyler Forehand, Julie Lankiewicz, Micaela H Coady, Lena Portillo, Jalpa Sarup-Patel, John A Jernigan, Jonathan B Perlin, Richard Platt, ABATE Infection trial team

Decolonisation with universal chlorhexidine bathing and targeted mupirocin for MRSA carriers did not significantly reduce multidrug-resistant organisms in non-critical-care patients.

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 Introduction Methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infection (BSI) is a major cause of morbidity and mortality in hospitalized patients. Ceftaroline fosamil (CPT) is the only available beta-lactam antibiotic with in vitro and in vivo activities against MRSA. There is currently limited clinical experience with CPT in complicated MRSA BSI. Materials and Methods We report a series of eight patients, including three whose strains had reduced susceptibility to vancomycin. Results CPT monotherapy was successfully used as salvage therapy for complicated MRSA BSI. The median time to documented clearance was 7 days. Conclusion Ceftaroline monotherapy is effective for clearance of refractory MRSA BSI related to implanted devices, endocarditis, and orthopedic infections.…

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.…

Geriak, M., Haddad, F., Rizvi, K., Rose, W., Kullar, R., LaPlante, K., Yu, M., Vasina, L., Ouellette, K., Zervos, M., Nizet, V., Sakoulas, G.

Vancomycin (VAN) and daptomycin (DAP) are approved as monotherapy for methicillin-resistant Staphylococcus aureus (MRSA) bacteremia. A regimen of daptomycin plus ceftaroline (DAP+CPT) has shown promise in published case series of MRSA salvage therapy, but no comparative data exist to compare up front DAP+CPT head-to-head vs. standard monotherapy as initial treatment.In a pilot study, we evaluated 40 adult patients who were randomized to receive DAP 6-8 mg/kg/d + CPT 600 mg IV q8 h (n=17) or standard monotherapy (n=23) with vancomycin (VAN, dosed to achieve serum trough concentrations 15-20 mg/L, n=21) or DAP 6-8 mg/kg/d (n=2). Serum drawn on the first day of bacteremia was sent to a reference laboratory post-hoc for measurement of IL-10 concentrations and correlation to in-hospital mortality.Sources of bacteremia, median Pitt bacteremia scores, Charlson comorbidity indices, and median serum IL-10 serum concentrations were similar in both groups. Although the study was initially designed to examine bacteremia duration, we observed an unanticipated in-hospital mortality difference of 0% (0/17) for combination and 26% (6/23) for monotherapy (P=0.029), causing us to halt the study. Among patients with IL-10 > 5 pg/mL, 0% (0/14) died in the DAP+CPT group vs. 26% (5/19) in the monotherapy group (P=0.057). Here we share the full results of this preliminary (but aborted) assessment of early DAP+CPT versus standard monotherapy in MRSA bacteremia, hoping to encourage a more definitive clinical trial of its potential benefits against this leading cause of infection associated mortality.…

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.…

Eléonore Bulliard, Bruno Grandbastien, Laurence Senn, Gilbert Greub, Dominique S. Blanc

Screening for Methicillin-resistant Staphylococcus aureus (MRSA) is part of many recommendations to control MRSA. Several rapid PCR tests are available commercially and updated versions are constantly released. We aimed to evaluate the performance of three consecutive versions (G3, Gen3 and NxG) of the XpertMRSA test.

Abstract Purpose Individuals with methicillin-resistant Staphylococcus aureus (MRSA) skin and soft tissue infection (SSTI) can be simultaneously colonized with MRSA on multiple body sites. Using whole genome sequencing (WGS), the intrahost relatedness of MRSA colonization and infection isolates was investigated. Methods In the context of a prospective case–control study of SSTI, we analyzed colonization and infection isolates from US Army Infantry trainees with purulent infection due to MRSA. At the time of clinical presentation for SSTI, culture swabs were obtained from the infection site, as well as from the patient’s nasal, oral, inguinal, and perianal regions. S. aureus culture and susceptibility was performed by standard methods. DNA from MRSA isolates was extracted and libraries were produced. Sequences were generated on an Illumina MiSeq, sequence reads were assembled, and single nucleotide variant (SNV) data were analyzed. Results Of 74 trainees with MRSA SSTI, 19 (25.7%) were colonized with MRSA. Ten (52.6%) were colonized on more than one body site. Colonization frequency by anatomic site was as follows: inguinal region (33%), nasal region (30%), perianal region (22%), and oral region (14%). A total of 36 MRSA colonization isolates were characterized. The intrahost median number of SNVs between infection and colonization isolates was 17. Among trainees with recurrent MRSA SSTI, limited intrahost diversity suggests that persistent colonization is a major contributor to recurrence risk. Conclusions Among military trainees with MRSA SSTI, genomic characterization of infection and colonization isolates revealed a high degree of strain relatedness. Single acquisition events may account for MRSA colonization and infection in this population.…

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 

Edit Urbán, Gregory G. Stone

In 2018, the European Committee on Antimicrobial Susceptibility Testing (EUCAST) introduced an intermediate breakpoint for ceftaroline against Staphylococcus aureus. The objective of this study was to compare data on resistance to ceftaroline among methicillin-resistant S. aureus (MRSA) isolates using versions 7.1 (March 2017) and 8.0 (January 2018) of the EUCAST breakpoints.

Rich, H. E., McCourt, C. C., Zheng, W. Q., McHugh, K. J., Robinson, K. M., Wang, J., Alcorn, J. F.

Influenza kills 30-40,000 people each year in the United States, and causes ten times as many hospitalizations. A common complication of influenza is bacterial super-infection, which exacerbates morbidity and mortality from the viral illness. Recently, MRSA has emerged as the dominant pathogen found in bacterial super-infection, with Streptococcus pneumoniae a close second. However, clinicians have few tools to treat bacterial super-infection. Current therapy for influenza/bacterial super-infection consists of treating the underlying influenza infection, adding various antibiotics which are increasingly rendered ineffective by rising bacterial multi-drug resistance. Several groups have recently proposed using the antiviral cytokine interferon lambda (IFN-) as a therapeutic for influenza, as administration of pegylated IFN- improves lung function and survival during influenza by reducing the overabundance of neutrophils in the lung. However, our data suggest that therapeutic IFN- impairs bacterial clearance during influenza super-infection. Specifically, mice treated with an adenoviral vector to overexpress IFN- during influenza infection exhibited increased bacterial burden upon super-infection with either MRSA or S. pneumoniae. Surprisingly, adhesion molecule expression, antimicrobial peptide production, and reactive oxygen species activity were not altered by IFN- treatment. However, neutrophil uptake of MRSA and S. pneumoniae was significantly reduced upon IFN- treatment during influenza super-infection in vivo. Together, these data support the theory that IFN- decreases neutrophil motility and function in the influenza-infected lung, which increases bacterial burden during super-infection. Thus, we believe caution should be exercised in the possible future use of IFN- as therapy for influenza.…

Daniela Dolce, Stella Neri, Laura Grisotto, Silvia Campana, Novella Ravenni, Francesca Miselli, Erica Camera, Lucia Zavataro, Cesare Braggion, Ersilia V. Fiscarelli, Vincenzina Lucidi, Lisa Cariani, Daniela Girelli, Nadia Faelli, Carla Colombo, Cristina Lucanto, Mariangela Lombardo, Giuseppe Magazzù, Antonella Tosco, Valeria Raia, Serena Manara, Edoardo Pasolli, Federica Armanini, Nicola Segata, Annibale Biggeri, Giovanni Taccetti

by Daniela Dolce, Stella Neri, Laura Grisotto, Silvia Campana, Novella Ravenni, Francesca Miselli, Erica Camera, Lucia Zavataro, Cesare Braggion, Ersilia V. Fiscarelli, Vincenzina Lucidi, Lisa Cariani, Daniela Girelli, Nadia Faelli, Carla Colombo, Cristina Lucanto, Mariangela Lombardo, Giuseppe Magazzù, Antonella Tosco, Valeria Raia, Serena Manara, Edoardo Pasolli, Federica Armanini, Nicola Segata, Annibale Biggeri, Giovanni Taccetti Background Few studies, based on a limited number of patients using non-uniform therapeutic protocols, have analyzed Methicillin-resistant Staphylococcus aureus (MRSA) eradication. Methods In a randomized multicenter trial conducted on patients with new-onset MRSA infection we evaluated the efficacy of an early eradication treatment (arm A) compared with an observational group (B). Arm A received oral rifampicin and trimethoprim/sulfamethoxazole (21 days). Patients’ microbiological status, FEV1, BMI, pulmonary exacerbations and use of antibiotics were assessed. Results Sixty-one patients were randomized. Twenty-nine (47.5%) patients were assigned to active arm A and 32 (52.5%) patients to observational arm B. Twenty-nine (47.5%) patients, 10 patients in arm A and 19 in arm B, dropped out of the study. At 6 months MRSA was eradicated in 12 (63.2%) out of 19 patients in arm A while spontaneous clearance was observed in 5 (38.5%) out of 13 patients in arm B. A per-protocol analysis showed a 24.7% difference in the proportion of MRSA clearance between the two groups (z = 1.37, P(Z>z) = 0.08). Twenty-seven patients, 15 (78.9%) out of 19 in arm A and 12 (92.3%) out of 13 in arm B, were able to perform spirometry. The mean (±SD) FEV1 change from baseline was 7.13% (±14.92) in arm A and -1.16% (±5.25) in arm B (p = 0.08). In the same period the BMI change (mean ±SD) from baseline was 0.54 (±1.33) kg/m2 in arm A and -0.38 (±1.56) kg/m2 in arm B (p = 0.08). At 6 months no statistically significant differences regarding the number of pulmonary exacerbations, days spent in hospital and use of antibiotics were observed between the two arms. Conclusions Although the statistical power of the study is limited, we found a 24.7% higher clearance of MRSA in the active arm than in the observational arm at 6 months. Patients in the active arm A also had favorable FEV1 and BMI tendencies.…

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.

Mody L, Washer L, Kaye K, et al.

AbstractBackgroundThe impact of healthcare personnel hand contamination in multidrug-resistant organism (MDRO) transmission is important and well studied; however, the role of patient hand contamination needs to be characterized further.MethodsPatients from 2 hospitals in southeast Michigan were recruited within 24 hours of arrival to their room and followed prospectively using microbial surveillance of nares, dominant hand, and 6 high-touch environmental surfaces. Sampling was performed on admission, days 3 and 7, and weekly until discharge. Paired samples of methicillin-resistant Staphylococcus aureus (MRSA) isolated from the patients’ hand and room surfaces were evaluated for relatedness using pulsed-field gel electrophoresis and staphylococcal cassette chromosome mec, and Panton-Valentine leukocidin typing.ResultsA total of 399 patients (mean age, 60.8 years; 49% male) were enrolled and followed for 710 visits. Fourteen percent (n = 56/399) of patients were colonized with an MDRO at baseline; 10% (40/399) had an MDRO on their hands. Twenty-nine percent of rooms harbored an MDRO. Six percent (14/225 patients with at least 2 visits) newly acquired an MDRO on their hands during their stay. New MDRO acquisition in patients occurred at a rate of 24.6/1000 patient-days, and in rooms at a rate of 58.6/1000 patient-days. Typing demonstrated a high correlation between MRSA on patient hands and room surfaces.ConclusionsOur data suggest that patient hand contamination with MDROs is common and correlates with contamination on high-touch room surfaces. Patient hand hygiene protocols should be considered to reduce transmission of pathogens and healthcare-associated infections.

Watkins R, Deresinski S.

AbstractOmadacycline, an aminomethylcycline, is a novel member of the tetracycline class of antibiotics. It has received approval by the U.S. Food and Drug Administration (FDA) for treatment of community-acquired bacterial pneumonia (CABP) and acute bacterial skin and skin structure infections (ABSSSIs) and is available in both oral and intravenous formulations. It is also being evaluated in clinical trials for the treatment of cystitis and pyelonephritis. The omadacycline molecule was designed to overcome tetracycline resistance and has broad spectrum activity that includes gram-positive bacteria, gram-negative bacteria, anaerobes, atypicals, and other drug-resistant strains like methicillin-resistant Staphylococcus aureus (MRSA), as well as Yersinia pestis and Bacillus anthracis, organisms of biodefense interest. Omadacycline has minimal drug-drug pharmacokinetic interactions and a favorable safety profile, with the most common adverse events being gastrointestinal symptoms.

Veronica Weterings, Jacobien Veenemans, Miranda van Rijen, Jan Kluytmans

We determined the prevalence of MRSA nasal carriage upon hospital admission, among patients who were screened preoperatively for nasal S. aureus carriage between 2010 and 2017. Secondly, we aimed to evaluate the prevalence of MRSA carriers without the standard risk factors.

Baines, S. L., Jensen, S. O., Firth, N., Goncalves da Silva, A., Seemann, T., Carter, G., Williamson, D. A., Howden, B. P., Stinear, T. P.

Staphylococcus aureus is a significant human pathogen whose evolution and adaptation has been shaped in part by mobile genetic elements (MGEs), facilitating global spread of extensive antimicrobial resistance. However, our understanding of the evolutionary dynamics surrounding MGEs is incomplete, in particular how changes in the structure of multidrug-resistant (MDR) plasmids may influence important staphylococcal phenotypes. Here, we undertook a population- and functional-genomics study of 212 methicillin-resistant S. aureus (MRSA) ST239 isolates collected over 32 years to explore the evolution of the pSK1 family of MDR plasmids; illustrating how these plasmids have co-evolved with and contributed to the successful adaptation of this persistent MRSA lineage. Using complete genomes and temporal phylogenomics we reconstructed the evolution of the pSK1 family lineage from its emergence in the late 1970s, with multiple structural variants arising. Plasmid maintenance and stability was linked to IS256- and IS257-mediated chromosomal integration and disruption of plasmid replication machinery. Overlaying genomic comparisons with phenotypic susceptibility data for gentamicin, trimethoprim and chlorhexidine, it appeared that pSK1 has contributed to enhanced resistance in ST239 MRSA through two mechanisms: (i) acquisition of plasmid-borne resistance mechanisms increasing rates of gentamicin resistance and reduced chlorhexidine susceptibility, and (ii) changes in plasmid configuration linked with further enhancement of chlorhexidine tolerance. While the exact mechanism of enhanced tolerance remains elusive, this research has uncovered a potential evolutionary response of ST239 MRSA to biocides, one which may contribute to the ongoing persistence and adaptation of this lineage within healthcare institutions.…

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.…

Dafna Yahav, Maria Abbas, Laila Nassar, Alia Ghrayeb, Daniel Kurnik, Daniel Shepshelovich, Leonard Leibovici, Mical Paul

by Dafna Yahav, Maria Abbas, Laila Nassar, Alia Ghrayeb, Daniel Kurnik, Daniel Shepshelovich, Leonard Leibovici, Mical Paul Introduction Current guidelines recommend maintaining vancomycin trough concentrations between 15–20 mg/L for serious methicillin resistant staphylococcus aureus (MRSA) infections. This recommendation is based on limited evidence. Methods A retrospective study including patients with vancomycin susceptible MRSA infections (MIC< = 2 mg/L), treated with vancomycin. We compared outcomes among patients attaining high (> = 15mg/L) vs low ( = 15 mg/L and clinical outcomes in patients with MRSA infections. In patients with MRSA pneumonia, vancomycin levels > = 15 mg/L were associated with higher clinical success rates. Further larger cohort studies are needed to define optimal vancomycin levels according to the site of infection.…

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.…

Janardhanan, J., Bouley, R., Martinez-Caballero, S., Peng, Z., Batuecas-Mordillo, M., Meisel, J. E., Ding, D., Schroeder, V. A., Wolter, W. R., Mahasenan, K. V., Hermoso, J. A., Mobashery, S., Chang, M.

The quinazolinones are a new class of antibacterials with in vivo efficacy against methicillin-resistant Staphylococcus aureus (MRSA). The quinazolinones target cell-wall biosynthesis and have a unique mechanism of action by binding to the allosteric site of penicillin-binding protein (PBP)2a. We investigated the potential for synergism of a lead quinazolinone with several antibiotics of different classes using the checkerboard and time-kill assays. The quinazolinone synergized with β-lactam antibiotics. The combination of the quinazolinone with the commercial piperacillin-tazobactam showed bactericidal synergy at sub-minimal-inhibitory concentrations of all three drugs. We demonstrated the efficacy of the triple-drug combination in a mouse MRSA neutropenic thigh-infection model. The proposed mechanism for the synergistic activity in MRSA involves inhibition of the β-lactamase by tazobactam, which protects piperacillin from hydrolysis, which can then inhibit its target PBP2. Furthermore, the quinazolinone binds to the allosteric site of PBP2a triggering the allosteric response. This leads to the opening of the active site, which in turn binds another molecule of piperacillin. In other words, PBP2a, which is not normally inhibited by piperacillin, becomes vulnerable to inhibition in the presence of the quinazolinone. The collective effect is the impairment of cell-wall biosynthesis, with bactericidal consequence. Two crystal structures for complexes of the antibiotics with PBP2a provide support for the proposed mechanism of action.…

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.

Westfall, C., Flores-Mireles, A. L., Robinson, J. I., Lynch, A. J. L., Hultgren, S., Henderson, J. P., Levin, P. A.

The antimicrobial triclosan is used in a wide range of consumer products ranging from toothpaste, cleansers, socks, and baby toys. A bacteriostatic inhibitor of fatty acid synthesis, triclosan is extremely stable and accumulates in the environment. Approximately 75% of adults in the US have detectable levels of the compound in their urine, with a sizeable fraction of individuals (>10%) having urine concentrations equal to or greater than the minimal inhibitory concentration for Escherichia coli and methicillin-resistant Staphylococcus aureus (MRSA). Previous work has identified connections between defects in fatty acid synthesis and accumulation of the alarmone guanosine tetraphosphate (ppGpp), which has been repeatedly associated with antibiotic tolerance and persistence. Based on these data, we hypothesized that triclosan exposure may inadvertently drive bacteria into a state in which they are able to tolerate normally lethal concentrations of antibiotics. Here we report that clinically relevant concentrations of triclosan increased E. coli and MRSA tolerance to bactericidal antibiotics as much as 10,000 fold in vitro and reduced antibiotic efficacy up to 100-fold in a mouse urinary tract infection model. Genetic analysis indicated that triclosan-mediated antibiotic tolerance requires ppGpp synthesis, but is independent of growth. These data highlight an unexpected and certainly unintended consequence of adding high concentrations of antimicrobials in consumer products, supporting an urgent need to reevaluate the costs and benefits of the prophylactic use of triclosan and other bacteriostatic compounds.…

See I, Mu Y, Albrecht V, et al.

AbstractBackgroundPrevious reports suggested that U.S. methicillin-resistant Staphylococcus aureus (MRSA) strain epidemiology has changed since the rise of USA300 MRSA. We describe invasive MRSA trends by strain type.MethodsData came from five CDC Emerging Infections Program sites conducting population-based surveillance and collecting isolates for invasive MRSA (i.e., from normally sterile body sites), 2005–2013. MRSA bloodstream infection (BSI) incidence/100,000 population was stratified by strain type and epidemiologic classification of healthcare exposures. Invasive USA100 vs USA300 case characteristics from 2013 were compared through logistic regression.ResultsFrom 2005–2013, USA100 incidence decreased most notably for hospital-onset (6.1 vs 0.9 / 100,000 persons, P

Abstract Background Osteomyelitis is often challenging to treat. This analysis examined the clinical experience of patients with gram-positive osteomyelitis treated with ceftaroline fosamil in the phase 4 Clinical Assessment Program and Teflaro® Utilization Registry (CAPTURE) study. Methods Data including patient demographics, past illnesses, risk factors, disease characteristics, antibiotic use, pathogens isolated, and clinical outcome were collected between September 2013 and February 2015 by review of randomly ordered patient charts from participating sites in the United States. Clinical success was defined as discontinuation of ceftaroline fosamil following clinical cure with no further need for antibiotics or clinical improvement with switch to another antibiotic treatment. Results A total of 150 patients with gram-positive osteomyelitis were treated with ceftaroline fosamil. Most patients (117/150; 78.0%) were treated with 600 mg ceftaroline fosamil per dose; 143/150 patients (95.3%) received a dose every 12 h. The majority (89/150 patients; 59.3%) had been previously diagnosed with diabetes mellitus or peripheral arterial disease. Osteomyelitis was associated with hardware in 32/150 patients (21.3%). Methicillin-resistant and methicillin-susceptible Staphylococcus aureus (MRSA; MSSA) were the most commonly isolated pathogens, observed in 93/150 (62.0%) and 21/150 (14.0%) patients, respectively. Clinical success with ceftaroline fosamil therapy was observed in 139/150 (92.7%) patients overall, 81/89 (91.0%) patients with diabetes or peripheral arterial disease, and 18/20 (90.0%) patients who had hardware implanted before ceftaroline fosamil therapy (none had hardware removed during therapy). Patients who received prior antibiotic therapy or ceftaroline fosamil as monotherapy experienced clinical success rates of 93.9% (107/114) and 91% (91/100), respectively. Among patients who received concurrent antibiotic therapy, the clinical success rate was 96.0% (48/50). Patients who were infected with MRSA or MSSA had clinical success rates of 92.5% (86/93) and 100% (21/21), respectively. A total of 2/150 (1.3%) patients discontinued ceftaroline fosamil therapy because of adverse events. Conclusions Clinical success rates with ceftaroline fosamil were high in patients with gram-positive osteomyelitis, including those with diabetes or peripheral arterial disease and those with MRSA or MSSA.…

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