Risk factors influencing clinical outcome in Staphylococcus aureus bacteraemia in a Turkish University Hospital

A total of 101 episodes of Staphylococcus aureus bacteraemia were evaluated for the factors influencing prognosis. The overall episode mortality rate and the mortality rate due to bacteraemia were 43.6 and 21.8%, respectively. Episodes with methicillin-resistant S. aureus (MRSA) bacteraemia had a significantly higher overall mortality rate (58.7 vs. 30.9%, P<0.01) and mortality rate due to bacteraemia (32.6 vs. 12.7%, P=0.02) when compared with episodes caused by methicillin-sensitive S. aureus (MSSA). The multivariate analysis revealed that the underlying disease, presence of infective endocarditis, septic shock and central intravascular catheter and methicillin resistance of S. aureus were the five independent risk factors associated with a higher mortality rate.     

Combination ceftaroline and daptomycin salvage therapy for complicated methicillin-resistant Staphylococcus aureus bacteraemia compared with standard of care

Complicated methicillin-resistant Staphylococcus aureus bloodstream infections (MRSA-BSIs), particularly those with delayed culture clearance, are associated with high mortality. Combination therapy with daptomycin and ceftaroline (DAP+CPT) represents a novel therapeutic approach to MRSA-BSI owing to synergistic bactericidal activity. This study aimed to compare DAP+CPT with historical standard of care (SoC) for treatment of complicated MRSA-BSI. This single-centre retrospective cohort study included patients with complicated MRSA-BSI at University of Colorado Hospital. Patients receiving DAP+CPT for ≥48 h between November 2013 and March 2020 or SoC with vancomycin or DAP ± gentamicin and/or rifampicin from November 2011 to December 2013 were compared. The primary outcome was clinical failure defined as a composite of MRSA-related mortality and recurrent infection at 60 days. A total of 60 patients received DAP+CPT (n = 30) or SoC (n = 30). Median age was 56 years and median Pitt bacteremia score was 3. Common infectious sites were endovascular (63%) and musculoskeletal (40%). DAP+CPT was associated with a numerically lower incidence of clinical failure compared with SoC (20% vs. 43%; P = 0.052). Multivariable analysis controlling for immunocompromised status (OR, 6.90, 95% CI 1.08–44.15), Charlson comorbidity index (OR, 1.12, 95% CI 0.90–1.39) and source control (OR, 0.35, 95% CI 0.08–1.46) associated DAP+CPT with 77% lower odds of clinical failure (OR, 0.23, 95% CI 0.06–0.89). In patients with complicated MRSA-BSI with delayed clearance, DAP+CPT trended towards lower rates of clinical failure than SoC and was significantly associated with decreased clinical failure after adjustment for baseline differences.     

Non-staphylococcal Gram-positive bacteraemia without a known source

This paper reviews bacteraemia without a known source caused by Gram-positive cocci, excluding staphylococci. These organisms include streptococci of groups A, B, C and G. Bacteraemia caused by nutritionally variant streptococci is also discussed.     

High vancomycin minimum inhibitory concentration is a predictor of mortality in meticillin-resistant Staphylococcus aureus bacteraemia

Failure of vancomycin in the treatment of meticillin-resistant Staphylococcus aureus (MRSA) bacteraemia has been reported despite full susceptibility of the organism to vancomycin. A retrospective observational cohort study including 137 patients with MRSA bacteraemia was performed at two centres in South Korea during 2009-2010. A total of 137 patients with MRSA bacteraemia receiving vancomycin therapy were enrolled during the study period. Isolates from 13 (9.5%) of the 137 patients had minimum inhibitory concentrations (MICs) ≥1 μg/mL. The 30-day cumulative survival was 53.8% for patients infected with isolates having a MIC≥1 μg/mL and 79.8% for patients infected with isolates having a MIC<1 μg/mL (log-rank test, P=0.026). Vancomycin MIC≥1 μg/mL [hazard ratio (HR)=7.0, 95% confidence interval (CI) 2.2-22.1; P=0.001], nosocomial acquisition of bacteraemia (HR=5.4, 95% CI 1.4-20.1; P=0.013), rapidly fatal underlying diseases (HR=20.5, 95% CI 3.9-106.4; P<0.001), presentation with septic shock (HR=8.4, 95% CI 3.0-23.3; P<0.001), presence of complicated infections (HR=5.6, 95% CI 2.0-15.8; P=0.001) and persistent MRSA bacteraemia for ≥3 days (HR=4.2, 95% CI 1.4-12.7; P=0.012) were independent predictors of 30-day mortality in patients with MRSA bacteraemia. In patients with high Pitt bacteraemia scores (Pitt score ≥2), the delay in initiation of vancomycin therapy was significantly different between non-survivors and survivors (2.4 days vs. 1.1 days; P=0.012). Vancomycin MIC≥1 μg/mL had a significant impact on mortality of patients with MRSA bacteraemia. These findings support early consideration of alternative anti-MRSA agents in patients with MRSA bacteraemia who have high vancomycin MICs as well as prompt initiation of anti-MRSA treatment in patients with MRSA bacteraemia, especially those with high Pitt scores.     

Outcome of patients with meticillin-resistant Staphylococcus aureus bacteraemia at an Emergency Department of a medical centre in Taiwan

The number of patients presenting to the Emergency Department (ED) with meticillin-resistant Staphylococcus aureus (MRSA) is increasing, but few studies focus on patients with bacteraemia. From January 2001 to June 2006 the clinical characteristics and outcome of 177 consecutive patients with MRSA bacteraemia visiting an ED of a university hospital were studied. The average age of the patients was 65.8 years. Healthcare-associated MRSA bacteraemia comprised 76.3% of all cases. Catheter-related bacteraemia was the most common type of infection (22.6%), followed by soft tissue infection (20.9%) and primary bacteraemia (15.3%). Different types of infection were significantly related to different outcome. In-hospital mortality was 33.3%, but the mortality decreased to 17.7% when patients with rapidly fatal disease and mortality within 3 days were excluded. All isolates exhibited lower susceptibility to vancomycin (minimum inhibitory concentration (MIC) 1-2mug/mL). Factors associated with mortality included severity of underlying illness, severity of bacteraemia and persistent bacteraemia. A detrimental effect of elevated MIC could not be demonstrated despite applying several definitions of patient outcome. Patients admitted to the ED with MRSA bacteraemia carry high overall mortality; however, the severity of underlying illness, severity of bacteraemia and persistent bacteraemia are correlated with mortality, but not vancomycin MICs (2mug/mL) of MRSA isolates.     

Staphylococcus aureus bacteraemia treatment outcomes in patients receiving ticagrelor vs a propensity-matched cohort receiving clopidogrel

ObjectivesTicagrelor may improve the outcomes in Staphylococcus aureus bacteraemia (SAB). However, treatment outcome data for these patients remain limited. The primary objective of this study was to characterize the outcomes of patients with SAB who received ticagrelor compared with a cohort who received clopidogrel.MethodsThis was a retrospective, nationwide propensity-matched analysis of patients with SAB who were prescribed ticagrelor or clopidogrel concomitantly with antistaphylococcal therapy. The primary outcome was the comparative all-cause 30-day mortality rate between propensity-matched groups.ResultsIn total, 1509 patients were prescribed concomitantly with ticagrelor or clopidogrel during treatment of S. aureus bacteraemia; of these, 194 patients were excluded from this study due to an inadequate number of antiplatelet doses within the first week of therapy (n=171) or non-admission to hospital (n=23). Of the remaining 1315 patients, 74 patients received ticagrelor and 1241 patients received clopidogrel. There was no significant difference in all-cause 30-day mortality between the groups [6/74 (8.1%) in the ticagrelor group vs 10/74 (13.5%) in the clopidogrel group; P=0.29]. Multi-variate logistic regression demonstrated that elevated aspartate aminotransferase, systolic blood pressure <90 mmHg, elevated serum creatinine and neurological comorbidity were independently associated with all-cause 30-day mortality.ConclusionsThis study found no difference in all-cause 30-day mortality between the two groups, although overall mortality appeared to be lower compared with other reports. Randomized controlled trials of P2Y12 inhibitors as adjunctive agents to antibiotic therapy for the treatment of serious S. aureus infections are warranted.     

Comparison of microbiological and clinical characteristics based on SCCmec typing in patients with community-onset meticillin-resistant Staphylococcus aureus (MRSA) bacteraemia

Molecular identification methods based on the staphylococcal cassette chromosome mec (SCCmec) genotype are more reliable than clinical risk factors and demographic data for differentiating community-acquired and healthcare-associated (HCA) meticillin-resistant Staphylococcus aureus (MRSA). However, patients with community-onset (CO) MRSA infections, defined as a culture-positive sample obtained <48 h after admission and from patients with HCA risk factors, have been infrequently studied. This study compared the clinical profiles of different SCCmec genotypes in this group of patients. From 2004 to 2008, the clinical profiles of 122 non-repetitive patients with CO-MRSA infections at a tertiary medical centre in Taiwan were retrospectively recorded and the molecular characteristics of the isolates were examined. The proportion of SCCmec IV/V genotypes increased from 9.5% to 35.3% from 2004 to 2008. There were no differences in demographic data, underlying diseases, invasive procedures or outcomes between the SCCmec II/III and IV/V groups, except that patients with SCCmec II/III genotypes tended to have more HCA risk factors (3.1 vs. 2.4; P = 0.008). Multivariate logistic regression analysis revealed that having at least four HCA risk factors was independently associated with SCCmec II/III. The sensitivity of recovering SCCmec IV/V genotypes from patients with less than four HCA risk factors was 89.3%. This study revealed the emergence of SCCmec IV/V genotypes in CO-MRSA infections. Although the clinical characteristic boundaries between SCCmec II/III and IV/V diminished, having at least four HCA risk factors made the presence of SCCmec IV/V genotypes less likely in patients with CO-MRSA infections.     

Staphylococcus aureus bacteriuria and surgical site infections by methicillin-resistant Staphylococcus aureus

Surgical site infection (SSI) remains an important cause of morbidity among hospitalized patients. We reviewed 421 patients who underwent open urological operations between January 1993 and December 1997 in our institute. Group I consisted of 259 patients who received uncontrolled antimicrobial prophylaxis (AMP) between 1993 and 1995. Group II consisted of 162 patients who received controlled AMP between 1996 and 1997. In group II, penicillins or first to second-generation cephalosporins was used and the duration of use for these agents regulated according to the wound class of each operation. The operations with clean wounds showed the lowest rate of SSI in both groups; the operations with contaminated wounds showed the highest rate of SSI (32.0% in group I and 33.3% in group II). There was no significant difference in the total rates of SSI between the two groups (P=0.216). The most frequently isolated bacterial species was methicillin-resistant Staphylococcus aureus (MRSA), isolated in 73.3% of the cases in group I and in 93.3% in group II. There was no significant difference in the incidence of MRSA isolation between the two groups (P=0.114). The controlled AMP could not lower the incidence of MRSA-induced SSIs. In SSI patients, 22.7% of group I and 35.7% in group II, had MRSA bacteriuria before operation. The prohibition of third-generation cephalosporins and shorter duration of AMP did not reduce the incidence of SSI induced by MRSA because MRSA was not the emerging microorganism but rather a resident in the urological ward. On the other hand, the total incidence of SSI did not increase after regulation of AMP. This finding suggests that older antibacterial agents can prevent infection, except those caused by resistant microorganisms such as MRSA. The effective counter-measure for the prevention of MRSA-induced SSI is needed.     

Lysine Inhibits Hemolytic Activity of Staphylococcus aureus and Its Application in Food Model Contaminated with Staphylococcus aureus

Highlights What are the main findings?

• Lysine inhibits hemolytic activity of S. aureus;
• Lysine inhibits the expression of toxin Hla of S. aureus;
• Lysine inhibits Hla oligomerization;
• Lysine attenuates S. aureus supernatant damage in mice and Caco-2 cells;
• Lysine inhibits the expression of Hla of S. aureus in a food model and had good biocompatibility.

What is the implication of the main finding?

• Lysine has the potential to be used as an anti- S. aureus preparation in the food industry.

AbstractAlpha-hemolysin (Hla) is one of the important exotoxins of Staphylococcus aureus (S. aureus) and can be used as a target to reduce the virulence of S. aureus. This study explored the inhibitory effect of Lysine (Lys) on Hla and its application in food safety. Lys significantly inhibited the expression of Hla at sub-inhibitory concentrations and directly interacted with Hla to interfere with its oligomerization and thus significantly inhibited its hemolytic activity. Notably, Lys attenuated S. aureus damage to mouse small intestine and Caco-2 cells and delayed mouse mortality. In the food model, Lys inhibited the expression of Hla of S. aureus and had no significant effect on the sensory score. Moreover, Lys had no obvious damage effect on the main organs of mice, which indicated that Lys has good biocompatibility and has the potential to be used in the food industry as an anti-S. aureus preparation.     

Daptomycin: a review of its use in the management of complicated skin and soft-tissue infections and Staphylococcus aureus bacteraemia

Daptomycin (Cubicin) is the first of a new class of antibacterials, the cyclic lipopeptides, and is approved for use in the treatment of complicated skin and soft-tissue or skin-structure infections (hereafter referred to as cSSTI) caused by Gram-positive bacteria and Staphylococcus aureus bacteraemia including right-sided infective endocarditis.Daptomycin has activity in vitro against a wide variety of Gram-positive bacteria, including meticillin-resistant S. aureus (MRSA) and vancomycin-resistant enterococci.When administered as a once-daily intravenous infusion, daptomycin was not inferior to standard parenteral therapy (vancomycin or semi-synthetic penicillins) in terms of clinical and microbiological efficacy in patients with cSSTI or S. aureus bacteraemia with or without infective endocarditis (including MRSA infection) and was well tolerated.With the advantage of once-daily administration and a low potential for drug interactions, daptomycin is a useful addition to the range of parenteral antibacterial agents available for the treatment of patients with cSSTI or S. aureus bacteraemia with or without right-sided infective endocarditis. Efficacy against both meticillin-susceptible S. aureus (MSSA) and MRSA infections makes daptomycin suitable for empirical therapy in patients with serious Gram-positive infections.     

长春市金葡菌耐药状况及耐甲氧西林金葡菌基因分型

目的调查长春地区临床分离金葡菌的耐药状况及Panton—Valentine杀白细胞素（PVL）分布情况；确定耐甲氧西林金葡菌（MRSA）染色体及葡萄球菌me~盒式染色体（SCCmec）基因分型。方法琼脂稀释法测定苯唑西林等17种抗菌药物对2004年6月～2005年1月长春市3家教学医院临床标本分离的83株金葡菌的最低抑菌浓度（MIC）；聚合酶链式反应（PCR）进行金葡菌的PVL基因检测；脉冲场凝胶电泳（PFGE）对MRSA菌株作染色体同源性分析。多重PCR方法检测MRSA的SCCmec基因分型。结果83株金葡菌中MRSA12株（占14．5％）；金葡菌PVL的基因阳性7株（占8．4％）。MRSA对β-内酰胺类、红霉素、克林霉素、庆大霉素、四环素、氟喹诺酮类耐药率均超过90％，对氯霉素、利福平耐药率分别为8．3％、58．3％。未发现对糖肽类及复方磺胺甲嗯唑耐药的MRSA。甲氧西林敏感金葡菌（MSSA）对青霉素G、红霉素、克林霉素、四环素、庆大霉素耐药率分别为95．8％、67．6％、49．3％、45．1％、26．8％，对头孢菌素、氯霉素、利福平、氟喹诺酮类、复方磺胺甲曙唑耐药率均低于20％。MRSA的PFGE显示为A、B两种类型，以A型为主，占92％（11／12），三家医院均有分布。MRSA的SCCmec分型．Ⅲ型为主75％（9／12）。结论长春市MRSA发生率低于国内报道平均水平；MRSA为两种不同类型克隆株，在不同医院间存在克隆传播；未发现社区获得性MRSA菌株。     

耐甲氧西林金葡菌到万古霉素高度耐药金葡菌的发展及其感染的药物治疗

随着万古霉素用量增加,耐甲氧西林金葡菌(MRSA)对万古霉素敏感性逐渐下降.依据其对万古霉素敏感性的差异可分成异质性万古霉素中度耐药金葡菌(hVISA)、万古霉素中度耐药金葡菌(VISA)和万古霉素高度耐药金葡菌(VRSA)等3类.本文简要综述卜述3类金葡菌的发展、相关耐药机制及其感染的药物治疗现状.