Comparison of Clinical Outcomes for Glycopeptides and Beta-Lactams in Methicillin-Susceptible Staphylococcus Aureus Bloodstream Infections.
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ABSTRACT: Purpose
This study aimed to provide compelling evidence of anti-staphylococcal beta-lactam use for methicillin-susceptible Staphylococcus aureus bloodstream infection (MSSA BSI).Materials and methods
We retrospectively collected data on patients with MSSA BSI who were admitted to two academic tertiary-care hospitals from 2010 to 2018. Only patients who received nafcillin, cefazolin, vancomycin, or teicoplanin as definitive therapy were included. The primary outcome was 28-day mortality. To perform unbiased comparisons between both treatments, we used inverse probability of treatment weighting (IPTW) analysis.Results
A total of 359 patients were divided into two groups based on the definitive therapy used: beta-lactams (n=203), including nafcillin or cefazolin; and glycopeptides (n=156), including vancomycin or teicoplanin. In the IPTW analysis, glycopeptides were associated with significantly increased odds of 28-day mortality (adjusted odds ratio, 3.37; 95% confidence interval, 1.71-6.61; p<0.001). The rate of primary outcome in prespecified subgroups was largely consistent with the main analysis.Conclusion
Definitive therapy with beta-lactams in patients with MSSA BSI was associated with lower 28-day mortality compared to definitive therapy with glycopeptides.
SUBMITTER: La YJ
PROVIDER: S-EPMC9226830 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundBloodstream infections due to Staphylococcus aureus cause significant patient morbidity and mortality worldwide. Of major concern is the emergence and spread of methicillin-resistant S. aureus (MRSA) in bloodstream infections, which are associated with therapeutic failure and increased mortality.MethodsWe generated high quality draft genomes from 323 S. aureus blood culture isolates from patients diagnosed with bloodstream infection at the Dartmouth-Hitchcock Medical Center, New Hampshire, USA in 2010-2018.ResultsIn silico detection of antimicrobial resistance genes revealed that 133/323 isolates (41.18%) carry horizontally acquired genes conferring resistance to at least three antimicrobial classes, with resistance determinants for aminoglycosides, beta-lactams and macrolides being the most prevalent. The most common resistance genes were blaZ and mecA, which were found in 262/323 (81.11%) and 104/323 (32.20%) isolates, respectively. Majority of the MRSA (102/105 isolates or 97.14%) identified using in vitro screening were related to two clonal complexes (CC) 5 and 8. The two CCs emerged in the New Hampshire population at separate times. We estimated that the time to the most recent common ancestor of CC5 was 1973 (95% highest posterior density (HPD) intervals: 1966-1979) and 1946 for CC8 (95% HPD intervals: 1924-1959). The effective population size of CC8 increased until the late 1960s when it started to level off until late 2000s. The levelling off of CC8 in 1968 coincided with the acquisition of SCCmec Type IV in majority of the strains. The plateau in CC8 also coincided with the acceleration in the population growth of CC5 carrying SCCmec Type II in the early 1970s, which eventually leveled off in the early 1990s. Lastly, we found evidence for frequent recombination in the two clones during their recent clonal expansion, which has likely contributed to their success in the population.ConclusionsWe conclude that the S. aureus population was shaped mainly by the clonal expansion, recombination and co-dominance of two major MRSA clones in the last five decades in New Hampshire, USA. These results have important implications on the development of effective and robust strategies for intervention, control and treatment of life-threatening bloodstream infections.
| S-EPMC8215799 | biostudies-literature
Project description:PurposeAn increasing burden of Staphylococcus aureus bloodstream infections (BSI), despite a decrease in the percentage of methicillin-resistant S. aureus (MRSA), was described recently in other European countries. The main aim of this study was to analyse recent temporal trends of S. aureus, methicillin-susceptible S. aureus (MSSA) and MRSA BSI for Switzerland as well as the different linguistic regions within Switzerland. An additional aim was to estimate potential differences among patient-based and epidemiological risk factors.MethodsA retrospective observational study was conducted in Switzerland over a period of 14 years (2008-2021). Trends in S. aureus, MSSA and MRSA BSI were analysed by applying linear regression models.ResultsStaphylococcus aureus BSI increased by + 30% from 19.7 to 25.6 cases per 100,000 inhabitants between 2008 and 2021 (P < 0.01) in Switzerland. Thereof, MSSA increased by + 37% from 17.8 to 24.4 cases per 100,000 inhabitants (P < 0.01). MRSA decreased from 1.9 to 1.2 cases per 100,000 inhabitants (P < 0.01), which was driven by decreasing incidence in the French-speaking region. MSSA BSI increased significantly (P < 0.01) in both linguistic regions. A further stratification revealed that incidence increased the most in male patients of the age group ≥ 80 years of the German-speaking region.ConclusionThe increasing health burden of MSSA BSI in Switzerland indicates that not only proportions of resistant microorganisms but also total BSI incidences should be monitored. In addition, data stratification revealed that the increase was mainly driven by an increasing incidence in elderly males of the German-speaking region.
| S-EPMC10352440 | biostudies-literature
Project description:ObjectivesStandard once-daily dosing of ceftriaxone may not lead to adequate antibiotic exposure in all cases of Staphylococcus aureus bacteraemia (SAB). Therefore, we compared clinical effectiveness of empirical antibiotic treatment with flucloxacillin, cefuroxime and ceftriaxone in adult patients with MSSA bacteraemia.MethodsWe analysed data from the Improved Diagnostic Strategies in Staphylococcus aureus bacteraemia (IDISA) study, a multicentre prospective cohort study of adult patients with MSSA bacteraemia. Duration of bacteraemia and 30 day SAB-related mortality were compared between the three groups using multivariable mixed-effects Cox regression analyses.ResultsIn total, 268 patients with MSSA bacteraemia were included in the analyses. Median duration of empirical antibiotic therapy was 3 (IQR 2-3) days in the total study population. Median duration of bacteraemia was 1.0 (IQR 1.0-3.0) day in the flucloxacillin, cefuroxime and ceftriaxone groups. In multivariable analyses, neither ceftriaxone nor cefuroxime was associated with increased duration of bacteraemia compared with flucloxacillin (HR 1.08, 95% CI 0.73-1.60 and HR 1.22, 95% CI 0.88-1.71). In multivariable analysis, neither cefuroxime nor ceftriaxone was associated with higher 30 day SAB-related mortality compared with flucloxacillin [subdistribution HR (sHR) 1.37, 95% CI 0.42-4.52 and sHR 1.93, 95% CI 0.67-5.60].ConclusionsIn this study, we could not demonstrate a difference in duration of bacteraemia and 30 day SAB-related mortality between patients with SAB empirically treated with flucloxacillin, cefuroxime or ceftriaxone. Since sample size was limited, it is possible the study was underpowered to find a clinically relevant effect.
| S-EPMC10154124 | biostudies-literature
Project description:Implant infections caused by methicillin-resistant Staphylococcus aureus (MRSA) can cause major complications during the perioperative period. Diclofenac, one of the most widely used nonsteroidal anti-inflammatory drugs, is often used to relieve pain and inflammation. In this study, it is found that high-dose diclofenac can inhibit the growth of MRSA, and does not easily induce drug-resistant mutations after continuous passage. However, low-doses diclofenac can resensitize bacteria to β-lactams, which help to circumvent drug resistance and improve the antibacterial efficacy of conventional antibiotics. Further, low-dose diclofenac in combination with β-lactams inhibit MRSA associated biofilm formation in implants. Transcriptomic and proteomic analyses indicate that diclofenac can reduce the expression of genes and proteins associated with β-lactam resistance: mecA, mecR, and blaZ; peptidoglycan biosynthesis: murA, murC, femA, and femB; and biofilm formation: altE and fnbP. Murine implant infection models indicate that diclofenac combined with β-lactams, can substantially alleviate MRSA infections in vivo. In addition, it is investigated that low dose diclofenac can inhibit MRSA antibiotic resistance via the mecA/blaZ pathway and related biofilms in implants. The synergistic effect of diclofenac and β-lactams might have promising applications for preventing perioperative infection, considering its multitarget effects against MRSA.
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Project description:IntroductionAnti-staphylococcal penicillins are generally accepted as first-line therapy for methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia, but their use may be limited by interstitial nephritis and acute kidney injury. Alternatives include first-generation cephalosporins including cefazolin.MethodsWe conducted a retrospective cohort study to compare adverse effects and clinical outcomes among patients with MSSA bacteremia treated with cefazolin or nafcillin. The primary endpoint was acute kidney injury (AKI), defined as a 0.3 mg/dL or 50% increase from baseline.ResultsIncidence of AKI was 27/82 (33%) versus 9/68 (13%) (p = 0.007) in the nafcillin and cefazolin arms, respectively. After adjusting for endocarditis and intensive care unit admission in multivariate logistic regression, nafcillin was an independent predictor of AKI [adj odds ratio (OR) = 2.74; 95% (CI) 1.1-6.6]. Patients who experienced AKI were more likely to have a prolonged intensive care unit stay.ConclusionRisk of nephrotoxicity is increased with nafcillin compared with cefazolin. Cefazolin should considered as a safer alternative to nafcillin for select patients with MSSA bacteremia.
| S-EPMC5446361 | biostudies-literature
Project description:BackgroundLivestock-associated methicillin-resistant Staphylococcus aureus clonal complex 398 (LA-MRSA CC398) is causing an increasing number of skin and soft tissue infections (SSTIs) in Denmark and other European countries with industrial pig production. Yet, its impact on MRSA bloodstream infections (BSIs) has not been well studied.MethodsWe investigated the clinical epidemiology of all human cases of LA-MRSA CC398 BSI during 2010-2015. Cases of LA-MRSA CC398 BSI were compared to cases of BSI caused by other types of MRSA and cases of SSTI caused by LA-MRSA CC398. Whole-genome sequence analysis was used to assess the phylogenetic relationship among LA-MRSA CC398 isolates from Danish pigs and cases of BSI and SSTI.ResultsThe number of LA-MRSA CC398 BSIs and SSTIs increased over the years, peaking in 2014, when LA-MRSA CC398 accounted for 16% (7/44) and 21% (211/985) of all MRSA BSIs and SSTIs, corresponding to 1.2 and 37.4 cases of BSI and SSTI per 1000000 person-years, respectively. Most patients with LA-MRSA CC398 BSI had no contact to livestock, although they tended to live in rural areas. LA-MRSA CC398 caused 24.3 BSIs per 1000 SSTIs among people with no livestock contact, which is similar to the ratio observed for other types of MRSA. Whole-genome sequence analysis showed that most of the BSI and SSTI isolates were closely related to Danish pig isolates.ConclusionsThis study demonstrates that the increasing number of LA-MRSA CC398 BSIs occurred in parallel with a much larger wave of LA-MRSA CC398 SSTIs and an expanding pig reservoir.
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Project description:Staphylococcus aureus invades eukaryotic cells. When methicillin-resistant S. aureus (MRSA) ATCC 33591 is phagocytized by human THP-1 macrophages, complete restoration of susceptibility to cloxacillin and meropenem is shown and the strain becomes indistinguishable from MSSA ATCC 25923 due to the acid pH prevailing in phagolysosomes (S. Lemaire et al., Antimicrob. Agents Chemother. 51:1627-1632, 2007). We examined whether this observation can be extended to (i) strains of current clinical and epidemiological interest (three hospital-acquired MRSA [HA-MRSA] strains, two community-acquired MRSA [CA-MRSA] strains, two HA-MRSA strains with the vancomycin-intermediate phenotype, one HA-MRSA strain with the vancomycin-resistant phenotype, and one animal [porcine] MRSA strain), (ii) activated THP-1 cells and nonprofessional phagocytes (keratinocytes, Calu-3 bronchial epithelial cells), and (iii) other beta-lactams (imipenem, oxacillin, cefuroxime, cefepime). All strains showed (i) a marked reduction in MICs in broth at pH 5.5 compared with the MIC at pH 7.4 and (ii) sigmoidal dose-response curves with cloxacillin (0.01x to 100x MIC, 24 h of incubation) after phagocytosis by THP-1 macrophages that were indistinguishable from each other and from the dose-response curve for methicillin-susceptible S. aureus (MSSA) ATCC 25923 (relative potency [50% effect], 6.09x MIC [95% confidence interval {CI}, 4.50 to 8.25]; relative efficacy [change in bacterial counts over the original inoculum for an infinitely large cloxacillin concentration, or maximal effect], -0.69 log CFU [95% CI, -0.79 to -0.58]). Similar dose-response curves for cloxacillin were also observed with MSSA ATCC 25923 and MRSA ATCC 33591 after phagocytosis by activated THP-1 macrophages, keratinocytes, and Calu-3 cells. By contrast, there was a lower level of restoration of susceptibility of MRSA ATCC 33591 to cefuroxime and cefepime after phagocytosis by THP-1 macrophages, even when the data were normalized for differences in MICs. We conclude that the restoration of MRSA susceptibility to beta-lactams after phagocytosis is independent of the strain and the types of cells but varies between beta-lactams.
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Project description:Select methicillin-susceptible Staphylococcus aureus (MSSA) strains may produce β-lactamases with affinity for first-generation cephalosporins (1GCs). In the setting of a high inoculum, these β-lactamases may promote the cleavage of 1GCs, a phenomenon known as the cefazolin inoculum effect (CzIE). We evaluated the prevalence and impact of CzIE on clinical outcomes among MSSA acute hematogenous osteomyelitis (AHO) cases. MSSA AHO isolates obtained from two children's hospitals between January 2011 and December 2018 were procured through ongoing surveillance studies. Isolates were tested for CzIE via a broth macrodilution assay using an inoculum of 107 CFU/ml; CzIE was defined as a cefazolin MIC of ≥16 μg/ml. Isolates were characterized by accessory gene regulator group (agr). The progression from acute to chronic osteomyelitis was considered an important outcome. A total of 250 cases with viable isolates were included. Notably, 14.4% of isolates exhibited CzIE with no observed temporal trend; and 4% and 76% of patients received a 1GC as an empirical and definitive therapy, respectively. CzIE isolates were more often resistant to clindamycin, belonged to agrIII, and associated with the development of chronic osteomyelitis. In multivariable analyses, agrIII, multiple surgical debridements, delayed source control, and CzIE were independently associated with progression to chronic osteomyelitis. A higher rate of chronic osteomyelitis was observed with CzIE isolates regardless of definitive antibiotic choice. CzIE is exhibited by 14.4% of MSSA AHO isolates in children. CzIE is independently associated with progression to chronic osteomyelitis in cases of AHO irrespective of final antibiotic choice. These data suggest that negative outcomes reported with CzIE may more accurately reflect strain-dependent virulence factors rather than true antibiotic failure.
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Project description:Prior studies of pediatric musculoskeletal infection have suggested that methicillin-resistant Staphylococcus aureus (MRSA) infections result in worse outcomes compared with infections with methicillin-susceptible S aureus (MSSA) strains. Based on these results, clinical prediction algorithms have been developed to differentiate between MRSA and MSSA early in a patient's clinical course. This study compares hospital outcomes for pediatric patients with MRSA and MSSA musculoskeletal infection presenting to the emergency department at a large tertiary care children's hospital.A retrospective study identified pediatric patients with S aureus musculoskeletal infection over a 5-year period (2008-2013) by sequential review of all pediatric orthopedic consults. Relevant demographic information, laboratory values, and clinical outcomes were obtained from the electronic medical record.Of the 91 identified cases of S aureus pediatric musculoskeletal infection, there were 49 cases of MRSA infection (53%) and 42 cases of MSSA infection (47%). There were no significant differences between MRSA and MSSA infections in median hospital length of stay (4.8 vs 5.7 days, P = .50), febrile days (0.0 vs 1.5 days, P = .10), and antibiotic duration (28 vs 34 days, P = .18). Methicillin-resistant S aureus infections were more likely to require operative intervention than MSSA infection (85% vs 62%, P = .15). A logistic regression model based on C-reactive protein, temperature, white blood cell count, pulse, and respiratory rate at presentation demonstrated poor ability to differentiate between MRSA and MSSA infection.The results demonstrated no significant differences between MSSA and MRSA musculoskeletal infections for most hospital outcomes measured. However, MRSA infections required more operative interventions than MSSA infections. In addition, a predictive model based on severity markers obtained at presentation was unable to effectively differentiate between MRSA and MSSA infection. The clinical utility and capacity for early differentiation of MRSA and MSSA depends on virulence patterns that may vary temporally and geographically.
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Project description:Novel therapies for methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infection (BSI) are needed in the setting of reduced antibiotic susceptibilities and therapeutic failure. Ceftaroline is a cephalosporin antibiotic with MRSA activity. Although not FDA approved for MRSA BSI, ceftaroline has generated much interest as a potential treatment option. However, detailed descriptions of its use in this setting remain limited. To address this, we conducted a retrospective, multicenter, observational study of adult patients with MRSA BSI treated with at least 72 h of ceftaroline from 2011 to 2015. Safety outcomes were examined in the overall cohort, while efficacy outcomes were examined among patients who had not cleared their BSI prior to ceftaroline initiation. Data were also stratified by ceftaroline monotherapy or combination therapy. Predictors of clinical failure on ceftaroline treatment were also sought. Overall, 211 patients were included in the safety population; Clostridium difficile infection, rash, and neutropenia occurred in 6 patients (2.8%), 7 patients (3.3%), and 3 patients (1.4%), respectively. Clinical success was observed in 86 (68.3%) of the 126 patients included in the efficacy population. The monotherapy and combination therapy subgroups had similar proportions of patients experiencing success (69.7 and 64.9%, respectively). The median BSI durations post-ceftaroline treatment were 2 days (interquartile range, 1 to 4 days) for monotherapy and 3 days (interquartile range, 1.5 to 5 days) for combination therapy. Higher acute physiology and chronic health evaluation II scores and comorbid malignancy independently predicted treatment failure. Ceftaroline appears effective for MRSA BSI as both monotherapy and combination therapy. However, comparative studies are needed to further delineate the role of ceftaroline in MRSA BSI treatment.
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