Methicillin-resistant Staphylococcus Aureus Ventilator-associated Pneumonia Research Articles

Ventilator-Associated Pneumonia Due to MRSA vs. MSSA: What Should Guide Empiric Therapy?

The guidelines on ventilator-associated pneumonia (VAP) recommend an empiric therapy against methicillin-resistant Staphylococcus aureus (MRSA) according to its prevalence rate. Considering the MRSA and MSSA VAP prevalence over the last 9 years in our tertiary care hospital, we assessed the clinical value of the MRSA nasal-swab screening in either predicting or ruling out MRSA VAP. We extracted the data of 1461 patients with positive bronchoalveolar lavage (BAL). Regarding the MRSA nasal-swab screening, 170 patients were positive for MRSA or MSSA. Overall, MRSA had a high prevalence in our ICU. Despite the COVID-19 pandemic, there was a significant downward trend in MRSA prevalence, while MSSA remained steady over time. Having VAP due to MRSA did not have any impact on LOS and mortality. Finally, the MRSA nasal-swab testing demonstrated a very high negative predictive value for MRSA VAP. Our results suggested the potential value of a patient-centered approach to improve antibiotic stewardship.

Effects of Different Inhalation Therapy on Ventilator-Associated Pneumonia in Ventilated COVID-19 Patients: A Randomized Controlled Trial.

The effect of routine inhalation therapy on ventilator-associated pneumonia (VAP) in mechanically ventilated patients with the coronavirus disease (COVID-19) has not been well-defined. This randomized controlled trial included 175 eligible adult patients with COVID-19 who were treated with mechanical ventilation at the University Hospital of Split between October 2020 and June 2021. Patients were randomized and allocated to a control group (no routine inhalation) or one of the treatment arms (inhalation of N-acetylcysteine; 5% saline solution; or 8.4% sodium bicarbonate). The primary outcome was the incidence of VAP, while secondary outcomes included all-cause mortality. Routine inhalation therapy had no effect on the incidence of bacterial or fungal VAP nor on all-cause mortality (p > 0.05). Secondary analyses revealed a significant reduction of Gram-positive and methicillin-resistant Staphylococcus aureus (MRSA) VAP in the treatment groups. Specifically, the bicarbonate group had a statistically significantly lower incidence of Gram-positive bacterial VAP (4.8%), followed by the N-acetylcysteine group (10.3%), 5% saline group (19.0%), and control group (34.6%; p = 0.001). This difference was driven by a lower incidence of MRSA VAP in the bicarbonate group (2.4%), followed by the N-acetylcysteine group (7.7%), 5% saline group (14.3%), and control group (34.6%; p < 0.001). Longer duration of ventilator therapy was the only significant, independent predictor of any bacterial or fungal VAP in the multivariate analysis (aOR 1.14, 95% CI 1.01–1.29, p = 0.038 and aOR 1.05, 95% CI 1.01–1.10, p = 0.028, respectively). In conclusion, inhalation therapy had no effect on the overall VAP incidence or all-cause mortality. Further studies should explore the secondary findings of this study such as the reduction of Gram-positive or MRSA-caused VAP in treated patients.

Predictive Value of the Methicillin-Resistant Staphylococcus aureus Nasal Swab for Methicillin-Resistant Staphylococcus aureus Ventilator-Associated Pneumonia in the Trauma Patient.

Background: Many trauma centers have empiric treatment algorithms for ventilator-associated pneumonia (VAP) treatment prior to culture results that include antibiotic agents for methicillin-resistant Staphylococcus aureus (MRSA) coverage that can have adverse effects. This is the only study to evaluate risk factors and MRSA nasal swabs to risk-stratify trauma patients for MRSA VAP, thereby potentially limiting the need for empiric vancomycin. Patients and Methods: This was a single institution retrospective cohort study. Adult patients admitted to the trauma intensive care unit (ICU) between January 2013 and December 2017 who had a MRSA nasal swab and subsequently met criteria for VAP were included. Demographics, risk factors for MRSA pneumonia, and culture results were collected. Results: A total of 140 patients met inclusion criteria. The negative predictive value (NPV) of MRSA nasal swab at predicting subsequent MRSA pneumonia was 97%. The sensitivity, specificity, and positive predictive value were 50.0%, 96.2%, and 44.4%, respectively. Smokers were more likely to develop MRSA pneumonia, odds ratio: 7.0 (p = 0.02). When considering non-smokers with a negative MRSA nasal swab, NPV was 100%. Conclusions: This is the only study to date that assesses the utility of MRSA nasal swab and risk factor data to guide empiric VAP antibiotic therapy in trauma patients. Smoking was found to be a risk factor for MRSA pneumonia. The use of MRSA nasal swabs in combination with smoking status to guide empiric use of MRSA coverage antibiotic agents is recommended because of a 100% NPV. When utilized, as many as 68% of patients may safely be spared MRSA coverage antibiotic agents and the related adverse effects.

Bronchoscopic Improvement of Tracheobronchitis Due to Methicillin-Resistant Staphylococcus aureus After Aerosolized Vancomycin: A Case Series.

Ventilator-associated tracheobronchitis (VAT) is an important risk factor for ventilator-associated pneumonia (VAP). The efficacy of aerosolized vancomycin (AV) in treating VAT has not been clearly demonstrated. Four mechanically ventilated patients with methicillin-resistant Staphylococcus aureus (MRSA) pneumonia were treated with an additional AV. AV (250 mg twice per day) was administered through a vibrating mesh device for 5 days. All patients were receiving intravenous vancomycin and had severe tracheobronchitis, based on bronchoscopic findings before or soon after additional AV treatment. After several days of AV treatment, follow-up bronchoscopies showed dramatic improvement of tracheobronchitis. All patients achieved microbiological eradication of MRSA. Finally, two of four patients survived through to hospital discharge. This case series study suggests a potential role of AV in the treatment of MRSA tracheobronchitis, which were accompanied by VAP. Clinical trial addressing the efficacy of AV in MRSA VAT and/or VAP should be needed.

Linezolid versus Vancomycin for the Treatment of Methicillin-Resistant &lt;i&gt;Staphylococcus aureus&lt;/i&gt; in Hospital-Acquired, Ventilator-Associated, and Healthcare-Associated Pneumonia at Tertiary Care Hospital

Aim: To evaluate morbidity and mortality rate, clinical cure rate and cost of linezolid versus vancomycin in patients who have hospital-acquired pneumonia (HAP), ventilator-associated pneumonia (VAP) or Healthcare-associated pneumonia (HCAP) caused by methicillin-resistant Staphylococcus aureus (MRSA). Methods: Retrospective analysis data. Data were collected for adult patients admitted to King Faisal Specialist Hospital and Research Centre-Jeddah (KFSH & RC-J) from January 2010 to May 2015. Method: A total of 88 patients with HAP, VAP and HCAP caused by MRSA treated with vancomycin (IV) or linezolid (IV or PO) either as empirically or directed therapy ≥ 7 days. They are retrospectively evaluated and analyzed. The primary end points are morbidity and mortality rate as well as clinical cure rate. The secondary end point is the cost analysis for each medication. Results: A total of 40 patients (ICU, n = 13 (32.5% and non ICU, n = 27 (67.5%)) were included in the study. Among vancomycin, n = 21 (52.5%); age (54.95 ± 18.255) and linezolid, n = 19 (74.5%); age (48.684 ± 25.593), there was no statistical differences in mortality and morbidity rate (P = 0.375). Clinical cure rate (fever improvement, 12 (57.1%) vs 12 (63.2%); P = 0.698, leukocytosis improvement, 15 (71.4%) vs 14 (73.7%); P = 0.873, purulent sputum improvement, 6 (28.6%) vs 4 (21.1%); P = 0.429, dyspnea improvement, 8 (38.1%) vs 3 (15.8%); P = 0.115,cough improvement 4 (19.0%) vs 4 (21.1%); P = 0.592, microbiological eradication of MRSA from sputum culture, 2 (9.5%) vs 6 (31.6%); P = 0.089 and improvement of radiographic finding (pulmonary infiltration), 17 (81.0%) vs 16 (84.2%); P = 0.559) of vancomycin vs linezolid, respectively. The cost analysis in the treatment of MRSA pneumonia with linezolid is statistical significantly higher than vancomycin. The mean cost of vancomycin = 185.9143 SR and of linezolid = 4547.3684 SR (P Conclusion: There are no statistical differences in mortality and morbidity rate and clinical cure rate between linezolid and vancomycin in the treatment of MRSA in HAP, VAP, and HCAP. However, the cost of linezlid is significantly higher than vancomycin during the treatment period of one patient.

Empiric Methicillin Resistant Staphylococcus aureus Coverage in the Early Ventilator Associated Pneumonia Window: If and When

Choice of empiric antibiotic(s) for early ventilator associated pneumonia (VAP) involves weighing the risks of potential infection with multi-drug resistant (MDR) pathogens against those of over-exposure to broad-spectrum agents. Although early VAP is believed to be rarely caused by MDR pathogens, the overall incidence of all methicillin resistant Staphylococcus aureus (MRSA) infections is increasing. We questioned if MRSA VAP is becoming more common and if these infections were occurring earlier in the patient's hospital course. We hypothesized that 1) early (2-4 d from intubation) VAP caused by MRSA is relatively uncommon and 2) those patients with early VAP because of MRSA had risk factors associated with a MDR organism infection. Bronchoscopies with lavage (BALs) from patients admitted to our SICU from 2010-2013 were reviewed. MRSA VAP was defined as growth of ≥10(5) cfu/mL from BAL. Multi-drug resistant risk factors included a previous MRSA infection or positive nasal swab, antibiotic use within 90 d, hospitalization for >5 d, hemodialysis, homelessness, intravenous drug use, and men having sex with men. In the 3-y period, there were 438 cases of VAP. Forty-seven specimens from 43 patients had quantitative microbiologic confirmation of MRSA VAP for an overall prevalence of 10.7%. Of patients with early VAP, three of 106 (2.8%) were MRSA positive. Culture results were graphed according to ventilator days ( Fig. 1 ). The median days ventilated at the time of MRSA VAP were 8 d (range 2-81). All of the early MRSA VAP patients had identifiable risk factors for MRSA infection. The negative predictive value for patients not having a risk factor was one. These data suggest that the incidence of MRSA VAP is stable. Those patients with early MRSA VAP demonstrated traditional MDR risk factors. Patients without risk factors in the early time period could effectively be ruled out from having MRSA VAP and likely do not require empiric MRSA coverage.

What is the best therapeutic approach to methicillin-resistant Staphylococcus aureus pneumonia?

The purpose of this review is to define what the best therapeutic approach is for the treatment of methicillin-resistant Staphylococcus aureus (MRSA) pneumonia. Although two meta-analyses reported conflicting findings, recent retrospective studies reported higher success rates in patients with MRSA pneumonia treated with linezolid when compared to vancomycin. Only registration trials are available for some anti-MRSA antibiotics, such as telavancin, ceftaroline, and ceftobiprole. Scarce information is available regarding the best therapeutic approach for MRSA community-acquired pneumonia. Linezolid seems to be a better choice than vancomycin for the treatment of MRSA ventilator-associated pneumonia. It is still unclear whether this affirmation holds for other forms of MRSA pneumonia. Further research is needed to define whether newer antibiotics are better alternatives than currently recommended agents.

The Impact of Antimicrobial Resistance and Aging in VAP Outcomes: Experience from a Large Tertiary Care Center

BackgroundVentilator associated pneumonia (VAP) is a serious infection among patients in the intensive care unit (ICU).MethodsWe reviewed the medical charts of all patients admitted to the adult intensive care units of the Massachusetts General Hospital that went on to develop VAP during a five year period.Results200 patients were included in the study of which 50 (25%) were infected with a multidrug resistant pathogen. Increased age, dialysis and late onset (≥5 days from admission) VAP were associated with increased incidence of resistance. Multidrug resistant bacteria (MDRB) isolation was associated with a significant increase in median length of ICU stay (19 vs. 16 days, p = 0.02) and prolonged duration of mechanical ventilation (18 vs. 14 days, p = 0.03), but did not impact overall mortality (HR 1.12, 95% CI 0.51–2.46, p = 0.77). However, age (HR 1.04 95% CI 1.01–1.07, p = 0.003) was an independent risk factor for mortality and age ≥65 years was associated with increased incidence of methicillin-resistant Staphylococcus aureus (MRSA) infections (OR 2.83, 95% CI 1.27–6.32, p = 0.01).ConclusionsMDRB-related VAP is associated with prolonged ICU stay and mechanical ventilation. Interestingly, age ≥ 65 years is associated with MRSA VAP.

Higher clinical success in patients with ventilator-associated pneumonia due to methicillin-resistant Staphylococcus aureus treated with linezolid compared with vancomycin: results from the IMPACT-HAP study.

IntroductionControversy exists regarding optimal treatment for ventilator-associated pneumonia (VAP) due to methicillin-resistant Staphylococcus aureus (MRSA). The primary objective of this study was to compare clinical success of linezolid versus vancomycin for the treatment of patients with MRSA VAP.MethodsThis was a multicenter, retrospective, observational study of patients with VAP (defined according to Centers for Disease Control and Prevention criteria) due to MRSA who were treated with linezolid or vancomycin. MRSA VAP was considered when MRSA was isolated from a tracheal aspirate or bronchoalveolar lavage. Clinical success was evaluated by assessing improvement or resolution of signs and symptoms of VAP by day 14. After matching on confounding factors, logistic regression models were used to determine if an association existed between treatment arm and clinical success.ResultsA total of 188 patients were evaluated (101 treated with linezolid and 87 with vancomycin). The mean ± standard deviation Acute Physiology and Chronic Health Evaluation (APACHE) II score was 21 ± 11 for linezolid- and 19 ± 9 for vancomycin-treated patients (P = 0.041). Clinical success occurred in 85% of linezolid-treated patients compared with 69% of vancomycin-treated patients (P = 0.009). After adjusting for confounding factors, linezolid-treated patients were 24% more likely to experience clinical success than vancomycin-treated patients (P = 0.018).ConclusionsThis study adds to the evidence indicating that patients with MRSA VAP who are treated with linezolid are more likely to respond favorably compared with patients treated with vancomycin.

Methicillin-ResistantStaphylococcus aureusin Early Ventilator-Associated Pneumonia: Cause for Concern?

Ventilator-associated pneumonia (VAP) accounts for almost 90% of infections in mechanically ventilated patients and more than one-quarter of all patients requiring intubation, with associated mortality rates as high as 70%. The rise in methicillin resistance within the community has led to a national increase in methicillin-resistant Staphylococcus aureus (MRSA) rates in early VAP and associated healthcare expenditure. Trauma patients identified via an institutional VAP database were stratified by gender, age, severity of shock (24-h transfusions), and severity of injury. The primary outcome measure was evaluation of the incidence and trend of early MRSA VAP over a 6-y period. Secondary outcomes examined the adequacy of our current empiric antibiotic regimen as it pertained to outcome variables, including mortality. A total of 997 episodes of VAP were identified in 727 patients. Linear regression showed that the incidence of early Staphylococcus aureus (SA) VAP was stable over the 6-y period (slope=-0.911; p=0.490). Over the same 6 y, however, the percentage of MRSA in early SA VAP (slope=3.95; p=0.0154) and the incidence of early MRSA VAP increased. No difference in mortality was detected between early methicillin-susceptible SA and early MRSA VAP. After adjustment for age, ISS, and 24-h transfusion requirements, early MRSA was not an independent predictor of mortality (odds ratio [OR], 0.815; p=0.59). Although the incidence of early SA VAP with methicillin resistance increased significantly within the first 7 d of admission, this study showed no difference in mortality and resource utilization between early VAP from MRSA and other causative organisms, despite lack of empiric MRSA coverage.

Epidemiology and Outcome of Pneumonia Caused by Methicillin-Resistant Staphylococcus aureus (MRSA) in Canadian Hospitals

BackgroundMRSA remains a leading cause of hospital-acquired (HAP) and healthcare-associated pneumonia (HCAP). We describe the epidemiology and outcome of MRSA pneumonia in Canadian hospitals, and identify factors contributing to mortality.MethodsProspective surveillance for MRSA pneumonia in adults was done for one year (2011) in 11 Canadian hospitals. Standard criteria for MRSA HAP, HCAP, ventilator-associated pneumonia (VAP), and community-acquired pneumonia (CAP) were used to identify cases. MRSA isolates underwent antimicrobial susceptibility testing, and were characterized by pulsed-field gel electrophoresis (PFGE) and Panton-Valentine leukocidin (PVL) gene detection. The primary outcome was all-cause mortality at 30 days. A multivariable analysis was done to examine the association between various host and microbial factors and mortality.ResultsA total of 161 patients with MRSA pneumonia were identified: 90 (56%) with HAP, 26 (16%) HCAP, and 45 (28%) CAP; 23 (14%) patients had VAP. The mean (± SD) incidence of MRSA HAP was 0.32 (± 0.26) per 10,000 patient-days, and of MRSA VAP was 0.30 (± 0.5) per 1,000 ventilator-days. The 30-day all-cause mortality was 28.0%. In multivariable analysis, variables associated with mortality were the presence of multiorgan failure (OR 8.1; 95% CI 2.5-26.0), and infection with an isolate with reduced susceptibility to vancomycin (OR 2.5, 95% CI 1.0-6.3).ConclusionsMRSA pneumonia is associated with significant mortality. Severity of disease at presentation, and infection caused by an isolate with elevated MIC to vancomcyin are associated with increased mortality. Additional studies are required to better understand the impact of host and microbial variables on outcome.

Improved outcome of ventilator-associated pneumonia caused by methicillin-resistant Staphylococcus aureus in a trauma population

BackgroundThe treatment of ventilator-associated pneumonia (VAP) secondary to methicillin-resistant Staphylococcus aureus (MRSA) remains controversial. MethodsWe performed a review of all blunt trauma patients diagnosed with MRSA VAP from June 2005 to June 2011. VAP for the first 3 years was diagnosed by sputum aspiration and treated with vancomycin. For the last 3 years of the study period, VAP was diagnosed with bronchoalveolar lavage and treated with linezolid. ResultsMRSA VAP patients treated with vancomycin had an average hospital length of stay (LOS) of 49 days (range 9–99 days), an average intensive care unit (ICU) LOS of 43 days (range 6–98 days), and average ventilator days of 34.4 (range 3–76 days). Seventeen MRSA VAP patients treated with linezolid had an average hospital LOS of 27 days (range 11–61), an average ICU LOS of 22 days (range 10–42) days, and average ventilator days of 16.6 (range 2–42). ConclusionsTrauma patients who develop MRSA VAP appear to have fewer ventilator days and shorter ICU and hospital LOS when treated with linezolid.

Treatment of methicillin-resistant Staphylococcus aureus ventilator-associated pneumonia with high-dose vancomycin or linezolid

The purpose of this study was to determine the clinical cure rate of high-dose vancomycin for the treatment of methicillin-resistant Staphylococcus aureus (MRSA) ventilator-associated pneumonia (VAP) in critically ill trauma patients. Recent trials suggest that a traditional dose of 1 g q12 hours results in unacceptable cure rates for MRSA VAP. Thus, more aggressive vancomycin dosing has the potential to improve efficacy. Based on pharmacokinetic principles, the goal initial dose at the study center has been 20 mg/kg q12 hours or q8 hours since the 1990s. All patients admitted to the trauma intensive care unit from 1997 to 2008 diagnosed with MRSA VAP were retrospectively reviewed. Diagnosis required bacterial growth ≥ 100,000 colony forming units/mL from a bronchoscopic bronchoalveolar lavage, new or changing infiltrate, plus at least two of the following: fever, leukocytosis or leukopenia, or purulent sputum. Overall, 125 patients with 141 episodes of MRSA VAP were identified. Mean age was 47 years ± 21 years, median Injury Severity Score was 29 (22-43), 70% of patients were male, and the mean length of intensive care unit stay was 38 days ± 35 days. The mean initial vancomycin dose was 18.1 mg/kg/dose with a mean duration of therapy of 11 days. Clinical success was achieved in 88% (125 of 131) of episodes, with microbiological success in 89% (66 of 74) of episodes with a follow-up bronchoscopic bronchoalveolar lavage. Overall mortality was 20% (25 of 125), with death due to VAP in 12 of 25 deaths. Mean initial vancomycin trough concentrations were 10.6 mg/L in the clinical success group and 13.3 mg/L in the clinical failure group (p = not significant). High-dose vancomycin provided an acceptable cure rate for MRSA VAP in critically ill trauma patients. Therapeutic study, level III.

Clinical Outcomes of Linezolid vs Vancomycin in Methicillin-Resistant Staphylococcus aureus Ventilator-Associated Pneumonia

Vancomycin has been the treatment standard for methicillin-resistant Staphylococcus aureus (MRSA) infections, but clinical efficacy is limited. We report outcomes of a cohort with MRSA ventilator-associated pneumonia (VAP) treated with vancomycin vs linezolid. Retrospective analysis of 113 participants with MRSA VAP confirmed by bronchoscopy who have been initiated on therapy with either vancomycin or linezolid within 24 hours after bronchoscopy and completed ≥7 days of therapy during their hospitalization from July 2003 to June 2007. The primary endpoints were hospital survival and clinical cure, defined as resolution of signs and symptoms of VAP or microbiological eradication after completion of therapy along with clinical pulmonary infection score (CPIS) ≤6 at day 7 of therapy. At hospital discharge, 23/27 (85.2%) of linezolid and 72/86 (83.7%) of vancomycin recipients had survived (P = .672). In comparison to linezolid recipients, the adjusted odds ratio (OR) for survival was 0.72 (95% confidence interval [CI]: 0.16-3.27) with vancomycin therapy. Clinical cure was achieved in 24/27 (88.9%) of linezolid and 63/86 (73.3%) of vancomycin recipients (P = .066). Compared to linezolid recipients, the adjusted OR for clinical cure was 0.24 (95% CI: 0.05-1.10) with vancomycin therapy. Survival and clinical cure did not differ significantly between vancomycin recipients with trough level ≥15 and <15 μg/mL, respectively. Our results suggested no survival benefit but a trend toward higher cure rate with linezolid therapy. The optimal treatment of MRSA VAP requires further study through randomized, controlled trials.

Pneumonia due to methicillin-resistant Staphylococcus aureus: clinical features, diagnosis and management

The review highlights the clinical findings and the management of community-acquired, health-care associated and nosocomial pneumonia due to methicillin-resistant Staphylococcus aureus (MRSA). Although previously considered as a purely nosocomial event, community-acquired MRSA pneumonia is underestimated and is spreading worldwide. A retrospective study showed that almost half of patients with nonnosocomial MRSA pneumonia admitted to a large teaching hospital did not present established criteria for healthcare-associated infections. Recent data show that MRSA ventilator-associated pneumonia is associated with significantly higher mortality than ventilator-associated pneumonia caused by methicillin-susceptible Staphylococcus aureus. Therefore, prompt and appropriate therapy is essential. The optimal therapy for MRSA pneumonia has not been fully elucidated. Although vancomycin has been considered the gold standard for the treatment of MRSA infections, clinical failures have also been reported in the presence of in-vitro susceptibility. Linezolid may provide improved outcomes compared with vancomycin in patients with MRSA pneumonia, but validation in a prospective trial is currently lacking. Recently licensed tigecycline and dalbavancin, a drug in phase III trial, look promising. Animal models showed that immunization against a cytolytic toxin secreted by most Staphylococcus aureus strains protects against lethal pneumonia. Rapid recognition of possible staphylococcal infection in patients with severe pneumonia is essential. The treatment of MRSA pneumonia must be prompt and effective in order to allow a fast microbiological clearance and to successfully manage the infection.

Effect of linezolid in ventilator-associated pneumonia caused by MRSA

Evaluation of: Wunderink RG, Mendelson MH, Somero MS et al. Early microbiological response to linezolid vs vancomycin in ventilator-associated pneumonia due to methicillin-resistant Staphylococcus aureus. Chest 134, 1200–1207 (2008).Methicillin-resistant Staphylococcus aureus (MRSA) is an important cause of ventilator-associated pneumonia (VAP), especially in patients who develop VAP late in their hospital course. Clinical failure in MRSA VAP is unacceptably high. Linezolid is an oxazolidinone antimicrobial agent that demonstrates bacteriostatic activity against MRSA and has been demonstrated to be equivalent to vancomycin in the treatment of nosocomial pneumonia. Retrospective analysis of two randomized, double-blind, studies suggests that linezolid therapy may confer clinical benefit over vancomycin in patients with MRSA VAP. Linezolid demonstrates excellent penetration into the epithelial-lining fluid and this feature has been postulated to be integral to its therapeutic benefit in MRSA VAP. This article evaluates the findings of a recently published prospective, randomized, open-label, comparator-controlled, multicenter trial that aims to compare the early microbiological efficacy of linezolid with vancomycin in the treatment of VAP caused by MRSA.

Early Microbiological Response to Linezolid vs Vancomycin in Ventilator-Associated Pneumonia Due to Methicillin-Resistant Staphylococcus aureus

Methicillin-resistant Staphylococcus aureus (MRSA) is a common cause of ventilator-associated pneumonia (VAP). This prospective, open-label, multicenter clinical trial compared the early microbiological efficacy of linezolid (LZD) therapy with that of vancomycin (VAN) therapy in patients with MRSA VAP. A total of 149 patients with suspected MRSA VAP were randomized to receive either LZD, 600 mg, or VAN, 1 g every 12 h. Patients with baseline bronchoscopic BAL (BBAL) fluid quantitative culture findings that were positive for MRSA (>or= 10(4) cfu/mL) comprised the study population. The primary outcome was microbiological response (<or= 10(2) cfu/mL) in a second BBAL performed 72 to 96 h following the start of treatment. Thirty LZD-treated patients and 20 VAN-treated patients had microbiologically confirmed MRSA at baseline; 23 and 19 patients, respectively, underwent repeat BBAL. While a greater number of LZD-treated patients than VAN-treated patients achieved a microbiological cure (56.5% vs 47.4%, respectively; p = 0.757; 95% confidence interval, -21.1 to 39.4), this difference was not statistically significant. Nonstatistically significant differences were also seen for LZD-treated patients vs VAN-treated patients in terms of clinical cure (66.7% vs 52.9%, respectively), survival rate (86.7% vs 70.0%, respectively), and the mean duration of ventilation (10.4 vs 14.3 d, respectively), hospitalization (18.8 vs 20.1 d, respectively), ICU stay (12.2 vs 16.2 d, respectively), and time spent alive and not receiving mechanical ventilation (15.5 vs 11.1 d, respectively). Three patients who had been extubated prior to undergoing repeat BBAL had been randomized to receive LZD therapy. Early microbiological cure rates were not statistically significantly higher with LZD therapy than with VAN therapy despite trends in all secondary clinical outcomes favoring LZD therapy. These results suggest that any beneficial effect of LZD therapy may be due to factors other than increased bacterial clearance. Clinicaltrials.gov Identifier: NCT00572559.

Emergence of Staphylococcal Cassette ChromosomemecType IV Methicillin-ResistantStaphylococcus aureusas a Cause of Ventilator-Associated Pneumonia

Staphylococcal cassette chromosome mec (SCCmec) type IV methicillin-resistant Staphylococcus aureus (MRSA) strains were identified in 8 (19.5%) of 41 consecutive patients with MRSA ventilator-associated pneumonia (VAP) in this retrospective, observational study. There were no significant differences in VAP severity and crude mortality rates between patients with SCCmec type II strains and patients with SCCmec type IV strains.

Methicillin-resistant Staphylococcus aureus prolongs intensive care unit stay in ventilator-associated pneumonia, despite initially appropriate antibiotic therapy

To determine the impact of methicillin-resistant Staphylococcus aureus (MRSA) on length of stay in the intensive care unit (ICU) for patients with ventilator-associated pneumonia (VAP) and to control for the effect of initially inappropriate antibiotic treatment on outcomes by focusing only on persons who were given appropriate antibiotic therapy for their infection. Retrospective analysis of pooled, patient-level data from multiple clinical trials in VAP. Multiple ICUs in France. Persons with bronchoscopically confirmed VAP due to either MRSA or methicillin-susceptible S. aureus (MSSA) and who received initially appropriate antibiotic treatment. All persons with MRSA VAP received vancomycin (15 mg/kg intravenously, twice daily). None. We compared patients with MRSA VAP to persons with MSSA VAP. ICU length of stay represented the primary end point and ICU-free days served as a secondary end point. We recorded information regarding multiple confounders, including demographics, reasons for ICU admission and mechanical ventilation (MV), severity of illness at both ICU admission and time of diagnosis of VAP, and duration of mechanical ventilation before and following the onset of VAP. The final cohort included 107 patients, and one third of cases were due to MRSA. Despite receiving initially appropriate antibiotic treatment, median ICU length of stay was significantly longer for persons with MRSA infection (33 days vs. 22 days; p=.047). The median number of ICU-free days was concomitantly lower in MRSA VAP (0 days vs. 5 days; p=.011). Survival analysis employing a Cox proportional hazards model identified several predictors of remaining in the ICU: Pao2/Fio2 ratio at diagnosis of VAP, duration of MV before VAP, duration of MV after diagnosis of VAP, and reason for MV. Additionally, infection with MRSA as opposed MSSA doubled the probability of needing continued ICU care (hazard ratio, 2.08; 95% confidence interval, 1.09-3.95; p=.025). MRSA VAP independently prolongs the duration of ICU hospitalization, and in turn, increases overall costs, even for patients initially given appropriate antibiotic treatment. Confronting the adverse impact of MRSA will require efforts that address more than the initial antibiotic prescription.

Increase in Methicillin-Resistant Staphylococcus aureus Acquisition Rate and Change in Pathogen Pattern Associated with an Outbreak of Severe Acute Respiratory Syndrome

Background. An outbreak of severe acute respiratory syndrome (SARS) occurred in our 22-bed intensive care unit (ICU; Prince of Wales Hospital, Hong Kong, HKSAR, China) from 12 March to 31 May 2003, when only patients with SARS were admitted. This period was characterized by the upgrading of infection control precautions, which included the wearing of gloves and gowns all the time, an extensive use of steroids, and a change in antibiotic prescribing practices. The pattern of endemic pathogenic organisms, the rates of acquisition of methicillin-resistant Staphylococcus aureus (MRSA), and the rates of ventilator-associated pneumonia (VAP) were compared with those of the pre-SARS and post-SARS periods.Methods. Data on pathogenic isolates were obtained from the microbiology department (Prince of Wales Hospital). Data on MRSA acquisition and VAP rates were collected prospectively. MRSA screening was performed for all ICU patients. A case of MRSA carriage was defined as an instance in which MRSA was recovered from any site in a patient, and cases were classified as imported or ICU-acquired if the first MRSA isolate was recovered within 72 h of ICU admission or after 72 h in the ICU, respectively.Results. During the SARS period in the ICU, there was an increase in the rate of isolation of MRSA and Stenotrophomonas and Candida species but a disappearance of Pseudomonas and Klebsiella species. The MRSA acquisition rate was also increased: it was 3.53% (3.53 cases per 100 admissions) during the pre-SARS period, 25.30% during the SARS period, and 2.21% during the post-SARS period (P < .001). The VAP rate was high, at 36.5 episodes per 1000 ventilator-days, and 47% of episodes were caused by MRSA.Conclusions. A SARS outbreak in the ICU led to changes in the pathogen pattern and the MRSA acquisition rate. The data suggest that MRSA cross-transmission may be increased if gloves and gowns are worn all the time.