The impact of serum vancomycin levels and minimum inhibitory concentrations of methicillin-resistant Staphylococcus aureus on mortality in patients with nosocomial pneumonia

BACKGROUND:

Vancomycin is the treatment of choice for methicillin-resistant Staphylococcus aureus (MRSA) infections; however, treatment failure is not uncommon, even when the minimum inhibitory concentration (MIC) of the MRSA strain is within the susceptible range for vancomycin.

OBJECTIVE:

To describe the relationship between molecular markers such as the mecA and agrII genes, serum vancomycin levels and vancomycin MICs, and the 30-day mortality rate of patients with nosocomial MRSA pneumonia in an intensive care unit (ICU).

METHODS:

The present study was a prospective cohort study including all patients with MRSA hospital-acquired pneumonia or ventilator-associated pneumonia who were admitted to the ICU of a tertiary care hospital between June 2009 and December 2011. The MIC for vancomycin was determined using the E-test and broth microdilution methods. Variables analyzed included age, sex, comorbid conditions, serum vancomycin trough concentration, the Acute Physiology and Chronic Health Evaluation II (APACHE) score and the presence of the agrII gene. The primary outcome was mortality at 30 days.

RESULTS:

Thirty-six (42.4%) patients died within 30 days of the index MRSA culture. A multiple regression analysis that included the variables of MIC (determined using the E-test or broth microdilution methods), APACHE II score, serum vancomycin level and the presence of agrII revealed that only the APACHE II score was related to the 30-day mortality rate (P=0.03). Seven patients (9.0%) with isolates exhibiting an MIC ≥1.5 μg/mL according to the E-test method died, and nine patients (11.6%) survived (P=0.76). Of the patients for whom MICs were determined using the broth microdilution method, 11 (14.1%) patients with MICs of 1.0 μg/mL died, and 16 (20.5%) survived (P=0.92). The median APACHE II score of survivors was 22.5, and the median score of nonsurvivors was 25.0 (P=0.03). The presence of the agrII gene was not related to the 30-day mortality rate.

CONCLUSIONS:

Patients with severe hospital-acquired pneumonia presented with MRSA isolates with low to intermediate vancomycin MICs in the ICU setting. At the Hospital de Clínicas de Porto Alegre (Porto Alegre, Brazil), the 30-day mortality rate was high, and was similar among patients with severe hospital-acquired pneumonia infected with MRSA isolates that exhibited MICs of ≤1.5 μg/mL determined using the E-test method and ≤1.0 μg/mL determined using the broth microdilution method in those who achieved optimal serum vancomycin levels. The APACHE II scores which provides an overall estimate of ICU mortality were independently associated with mortality in the present study, regardless of the MICs determined. Molecular markers, such as the agrII gene, were not associated with higher mortality in the present study.     

Community-acquired methicillin-resistant Staphylococcus aureus pneumonia

Community-acquired methicillin-resistant Staphylococcus aureus is increasingly recognized as an important pathogen causing skin and soft tissue infections. We report a case of severe necrotizing pneumonia caused by community-acquired methicillin-resistant S. aureus in a peripartum woman. This case illustrates that community-acquired methicillin-resistant S. aureus must be considered as a potential pathogen in severe community-acquired pneumonia.     

Effect of vancomycin loading dose on clinical outcome in critically ill patients with methicillin-resistant Staphylococcus aureus pneumonia

BackgroundVancomycin is the treatment of choice for serious methicillin-resistant Staphylococcus aureus (MRSA) infections. Current guidelines recommend giving an initial loading dose (LD) of 25–30 mg/kg to rapidly increase the serum concentration. However, high-quality evidence for the clinical benefit of LD is lacking. Herein, we aim to examine the association between vancomycin LD and clinical outcome.MethodsA retrospective cohort study was conducted on adult patients treated for MRSA pneumonia with vancomycin in medical intensive care units from April 2016 to August 2018. MRSA pneumonia was defined by the Centers for Disease Control and National Healthcare Safety Network definition. The primary outcome was the clinical cure of pneumonia. Secondary outcome measures included time to pharmacokinetic (PK) target attainment, microbiological cure, acute kidney injury, and all-cause mortality.ResultsA total of 81 patients were included; of these 22 (27.2%) received LD. The mean initial dose was significantly higher in the LD group. Clinical cure was similar in both groups (68.2% vs. 66.1% in the LD and non-LD groups, respectively; P=0.860). No significant difference was observed in the microbiological cure, all-cause mortality, and incidence of acute kidney injury. Furthermore, no difference was observed in terms of time to PK target attainment (69.2 vs. 63.4 h in the LD and non-LD groups, respectively; P=0.624). Vancomycin minimum inhibitory concentration of <2 mg/L was identified as an independent predictive factor for clinical cure in multivariable analysis, whereas vancomycin LD was not.ConclusionsInitial LD is not associated with better clinical outcome or rapid pharmacological target attainment in critically ill patients with MRSA pneumonia. Further studies are warranted to provide better evidence for this widely recommended practice.     

Predictors of mortality for methicillin-resistant Staphylococcus aureus health-care-associated pneumonia: specific evaluation of vancomycin pharmacokinetic indices

OBJECTIVE: The goal of this investigation was to determine whether vancomycin pharmacokinetic indexes (eg, serum trough concentrations or area under the concentration curve [AUC] values) were associated with mortality for patients with health-care-associated pneumonia (HCAP) attributed to methicillin-resistant Staphylococcus aureus (MRSA). DESIGN: A retrospective, single-center, observational cohort study. SETTING: Barnes-Jewish Hospital, a 1,200-bed urban teaching facility. PATIENTS: Adult patients requiring hospitalization who were identified as having HCAP attributed to MRSA by BAL semi-quantitative cultures. INTERVENTIONS: Retrospective data collection from automated hospital, microbiology, and pharmacy databases. MEASUREMENTS AND MAIN RESULTS: One hundred two patients with MRSA HCAP were identified over a 6.5-year period. Thirty-two patients (31.4%) died during their hospitalization. The mean (+/- SD) vancomycin trough concentrations (13.6 +/- 5.9 vs 13.9 +/- 6.7 microg/mL, respectively; p = 0.866) and AUC values (351 +/- 143 vs 354 +/- 109 microg/h/mL, respectively; p = 0.941) did not differ between survivors and nonsurvivors. The stratification of the vancomycin trough concentrations and AUC values yielded no relationship with hospital mortality. CONCLUSIONS: We found no evidence that greater vancomycin trough concentrations or AUC values correlated with hospital outcome. Based on these results, aggressive dosing strategies for vancomycin (eg, trough concentrations of > 15 microg/mL) may not offer any advantage over traditional dose targets (range, 5 to 15 microg/mL).     

社区获得性耐甲氧西林金黄色葡萄球菌肺炎临床分析

目的 探讨社区获得性耐甲氧西林金黄色葡萄球菌肺炎的临床特点.方法 对16例确诊病例的临床资料进行回顾性研究.结果 16例确诊病例,13例无基础性疾病,9例合并休克,7例合并急性呼吸窘迫综合征,4例死亡;死亡者从出现症状入院至死亡平均时间为(5.9±6.1)d,生存者平均住院时间为(21.6±11.1)d;8例有流感样症状,7例有咯血,5例有白细胞减少,16例C-反应蛋白明显升高,平均为(211.1±121.9) mg/L,13例有多肺叶病变,9例有胸腔积液.结论 社区获得性耐甲氧西林金黄色葡萄球菌肺炎病情凶险,应提高对其临床特点的认识,优化综合治疗方案.     

Linezolid (PNU-100766) versus vancomycin in the treatment of hospitalized patients with nosocomial pneumonia: a randomized, double-blind, multicenter study.

Linezolid, the first oxazolidinone, is active against gram-positive bacteria, including multidrug-resistant strains. This multinational, randomized, double-blind, controlled trial compared the efficacy, safety, and tolerability of linezolid with vancomycin in the treatment of nosocomial pneumonia. A total of 203 patients received intravenous linezolid, 600 mg twice daily, plus aztreonam, and 193 patients received vancomycin, 1 g intravenously twice daily, plus aztreonam for 7-21 days. Clinical and microbiological outcomes were evaluated at test of cure 12-28 days after treatment. Clinical cure rates (71 [66.4%] of 107 for linezolid vs. 62 [68.1%] of 91 for vancomycin) and microbiological success rates (36 [67.9%] of 53 vs. 28 [71.8%] of 39, respectively) for evaluable patients were equivalent between treatment groups. Eradication rates of methicillin-resistant Staphylococcus aureus and safety evaluations were similar between treatment groups. Resistance to either treatment was not detected. Linezolid is a well-tolerated, effective treatment for adults with gram-positive nosocomial pneumonia.     

Enteral vancomycin to control methicillin-resistant Staphylococcus aureus outbreak in mechanically ventilated patients

BACKGROUND: Screening for and treating gut carriage of methicillin-resistant Staphylococcus aureus (MRSA) may control transmission and subsequent endemicity of MRSA. OBJECTIVE: Enteral vancomycin was evaluated as a measure to control an outbreak of MRSA infection in the intensive care unit (ICU). METHODS: During the 8-month study of sequential design, 176 patients were admitted, 65 (37%) of whom required a minimum of 3 days of ventilation. Forty-four patients were studied in the first 5 months, during which traditional measures were reinforced (control group). During the following 3 months, 13 of 21 patients developed MRSA carriage and received 2 g/day of enteral vancomycin, with high standards of hygiene maintained (treatment group). RESULTS: Thirty-three MRSA infections occurred in 22 patients (50%) in the control group, whereas 2 patients (9.5%) had 2 MRSA infections in the treatment group (P <.05 for carriage, infection rates, and episodes). Of the 33 MRSA infections in the control group, 27 were due to MRSA acquired in the ICU, whereas the 2 infections in the treatment group were primary endogenous (ie, caused by MRSA present in the patient's admission flora). The probability of developing an MRSA infection was reduced in patients receiving enteral vancomycin compared with patients in the control group (odds ratio, 0.37; 95% CI, 0.24-0.58). Enteral vancomycin significantly reduced the level of MRSA carriage; the mean carriage index was 1.01 in the control group versus 0.58 in the test group (P <.05). Neither vancomycin-resistant enterococci nor vancomycin-intermediate Staphylococcus aureus were isolated from either surveillance or diagnostic samples. CONCLUSIONS: The eradication of MRSA gut carriage by enteral vancomycin in a small subset of ICU patients was effective in the control of an MRSA outbreak.     

Community-acquired methicillin-resistant Staphylococcus aureus pneumonia: a clinical audit

Background and objective: Community‐associated methicillin‐resistant Staphylococcus aureus (CA‐MRSA) strains are primarily associated with skin and soft tissue infections; however, they are increasingly causing more invasive infections including severe community‐acquired pneumonia. The objective of this study was to describe the clinico‐pathological characteristics of community‐acquired MRSA pneumonia. Methods: A retrospective analysis of case records from January 2002 to August 2008 was performed on patients admitted with community‐acquired MRSA pneumonia to two large teaching hospitals. Results: Sixteen patients with community‐acquired MRSA pneumonia were identified. Their age ranged from 11 months to 86 years (median age; 30 years). Duration of symptoms before hospital presentation ranged from one to 21 days. Most patients had productive cough, fever and dyspnoea. The most common radiological presentation included multilobar consolidation (8/16), necrotizing consolidation (7/16) and empyema (5/16). Seven patients required intensive care support; four required ionotropic support and five required mechanical ventilation for a mean duration of 53 h and 6.6 days, respectively. Six patients underwent surgery (VATS or open thoracotomy). There was a mean delay of approximately 69 h (range; 18 h to 11 days) after presentation before appropriate MRSA antimicrobial treatment was initiated. Three patients died of complications from pneumonia, all within 72 h of presentation. Among survivors, the average length of hospital stay was 23.8 days (range; 10–49 days). Majority of survivors were left with mild residual radiological changes. Conclusions: Community‐acquired MRSA pneumonia is increasing and should be suspected in patients with severe community‐acquired pneumonia. There was a delay in initiation of appropriate antimicrobial treatment that could have lead to increased morbidity.     

耐甲氧西林金黄色葡萄球菌对万古霉素敏感性的变迁

目的　通过对近年来耐甲氧西林金黄色葡萄球菌 (MRSA)临床分离株对万古霉素抑菌圈直径的分析 ,研究MRSA对万古霉素敏感性的变化。方法　药敏试验采用纸片扩散法 (K B法 ) ,抑菌圈直径的比较采用t检验。结果　 1994～ 2 0 0 0年每年收集的临床分离的MRSA菌株数分别为 2 18、187、2 92、2 37、35 1、886和 6 5 2 ,各年菌株对万古霉素抑菌圈的平均直径 (mm)分别为 19 9、19 1、18 6、17 4、18 4、18 2和 17 8。 2 0 0 0年的 6 5 2株MRSA对万古霉素抑菌圈的平均直径 (17 8mm)明显小于1994年 2 18株MRSA的平均直径 (19 9mm) ,差异有显著性 (P <0 0 0 1)。 2 0 0 0年分离的MRSA对氯霉素、环丙沙星、红霉素、庆大霉素、四环素和复方新诺明等常用抗生素的耐药率均很高 ,其耐药百分率分别为 44 0 %、73 7%、89 1%、6 5 7%、6 1 0 %和 6 7 0 %。结论　 1994年到 2 0 0 0年MRSA对万古霉素的敏感性在逐年降低 ,加强金黄色葡萄球菌对万古霉素敏感性的监测非常必要。     

Slow response to vancomycin or vancomycin plus rifampin in methicillin-resistant Staphylococcus aureus endocarditis

OBJECTIVE: To determine the median response time to therapy with vancomycin alone or with vancomycin plus rifampin in patients with methicillin-resistant Staphylococcus aureus (MRSA) endocarditis. DESIGN: Cohort analysis of a randomized study. SETTING: University medical center. PATIENTS: Forty-two consecutive patients with MRSA endocarditis were randomly assigned to receive either vancomycin (group I) or vancomycin plus rifampin (group II) for 28 days. MEASUREMENTS: Clinical signs and symptoms were recorded, and blood cultures were obtained daily to determine the duration of bacteremia. MAIN RESULTS: The median duration of bacteremia was 9 days (7 days for group I and 9 days for group II). The median duration of fever for all patients and for each treatment group was 7 days. Six patients failed therapy, including three patients who died 5, 6, and 9 days after therapy was started, respectively. The other three patients who failed therapy required valve surgery on days 2, 22, and 27, respectively. Although patients had sustained bacteremia, no unusual complications were seen in either treatment group, and most patients responded to continued antibiotic therapy. CONCLUSIONS: Slow clinical response is common among patients with MRSA endocarditis who are treated with vancomycin or vancomycin plus rifampin. Nevertheless, few complications appear to be related solely to this sustained bacteremia.