Methicillin-resistant Staphylococcus Aureus Pneumonia Research Articles

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Introduction: Dexmedetomidine (DEX), a commonly used sedative in critically ill patients, is an alpha-2 adrenergic receptor agonist that is selective for alpha-2a receptors in low concentration and loses selectivity with higher concentrations. A hyperthermic response attributed to alpha-2c receptor overexpression has been previously described with MDMA (Ecstasy) in the literature, but a patient case demonstrating this concept has not been described with DEX. We describe a case of hyperthermic response attributable to DEX. Case: A 58 year old obese man with alcoholic cirrhosis, acquired thrombocytopenia, hypertension, and DMT2 presents with dyspnea, MRSA bacteremia and respiratory distress secondary to MRSA pneumonia. Despite appropriate initiation of antibiotic therapy and achievement of therapeutic vancomycin concentrations, mechanical ventilation was required on hospital day 2. The patient received etomidate, fentanyl and midazolam for intubation. The patient developed acute agitation (RASS +4), soon after and was started on DEX a rate of 1 mcg/kg/hr, which was increased to 1.5 mcg/kg/hr at 3 hours of therapy. The temperature recorded prior to intubation was 98° F. After 3 hours of DEX, the temperature increased to 99.4°F, and continued to increase over the next 12 hours to 104.3°F. At that time, drug-induced hyperthermia was suspected and DEX was discontinued. A maximum temperature recorded 90 minutes later was 105.1°F. A steady decrease to normothermia occurred over the next 12 hours. The patient remained afebrile, and was extubated on hospital day 4. Scheduled medications administered during the hyperthermic episode included vancomycin, cefepime, aspirin, famotidine, and diltiazem. No changes in therapeutic management of the patient could explain the hyperthermia demonstrated in this patient with the exception of the utilization of dexmedetomidine. Discussion: Activation of alpha-2c adrenergic receptor by high-dose dexmedetomidine may play a role in the hyperthermic response demonstrated in our patient. Recognition and discontinuation of DEX was associated with normalization of body temperature. Clinicians should be aware of this possible reaction.

A comparison of microbiology and demographics among patients with healthcare-associated, hospital-acquired, and ventilator-associated pneumonia: a retrospective analysis of 1184 patients from a large, international study

BackgroundAcceptance of healthcare-associated pneumonia (HCAP) as an entity and the associated risk of infection by potentially multidrug-resistant (MDR) organisms such as methicillin-resistant Staphylococcus aureus (MRSA), Pseudomonas and Acinetobacter have been debated. We therefore compared patients with HCAP, hospital-acquired pneumonia (HAP), and ventilator-associated pneumonia (VAP) enrolled in a trial comparing linezolid with vancomycin for treatment of pneumonia.MethodsThe analysis included all patients who received study drug. HCAP was defined as pneumonia occurring < 48 hours into hospitalization and acquired in a long-term care, subacute, or intermediate health care facility; following recent hospitalization; or after chronic dialysis.ResultsData from 1184 patients (HCAP = 199, HAP = 379, VAP = 606) were analyzed. Compared with HAP and VAP patients, those with HCAP were older, had slightly higher severity scores, and were more likely to have comorbidities. Pseudomonas aeruginosa was the most common gram-negative organism isolated in all pneumonia classes [HCAP, 22/199 (11.1%); HAP, 28/379 (7.4%); VAP, 57/606 (9.4%); p = 0.311]. Acinetobacter spp. were also found with similar frequencies across pneumonia groups. To address potential enrollment bias toward patients with MRSA pneumonia, we grouped patients by presence or absence of MRSA and found little difference in frequencies of Pseudomonas and Acinetobacter.ConclusionsIn this population of pneumonia patients, the frequencies of MDR gram-negative pathogens were similar among patients with HCAP, HAP, or VAP. Our data support inclusion of HCAP within nosocomial pneumonia guidelines and the recommendation that empiric antibiotic regimens for HCAP should be similar to those for HAP and VAP.

Predictive Value of Methicillin-Resistant Staphylococcus aureus (MRSA) Nasal Swab PCR Assay for MRSA Pneumonia

Pneumonia due to methicillin-resistant Staphylococcus aureus (MRSA) is associated with poor outcomes and frequently merits empirical antibiotic consideration despite its relatively low incidence. Nasal colonization with MRSA is associated with clinical MRSA infection and can be reliably detected using the nasal swab PCR assay. In this study, we evaluated the performance of the nasal swab MRSA PCR in predicting MRSA pneumonia. A retrospective cohort study was performed in a tertiary care center from January 2009 to July 2011. All patients with confirmed pneumonia who had both a nasal swab MRSA PCR test and a bacterial culture within predefined time intervals were included in the study. These data were used to calculate sensitivity, specificity, positive predictive value, and negative predictive value for clinically confirmed MRSA pneumonia. Four hundred thirty-five patients met inclusion criteria. The majority of cases were classified as either health care-associated (HCAP) (54.7%) or community-acquired (CAP) (34%) pneumonia. MRSA nasal PCR was positive in 62 (14.3%) cases. MRSA pneumonia was confirmed by culture in 25 (5.7%) cases. The MRSA PCR assay demonstrated 88.0% sensitivity and 90.1% specificity, with a positive predictive value of 35.4% and a negative predictive value of 99.2%. In patients with pneumonia, the MRSA PCR nasal swab has a poor positive predictive value but an excellent negative predictive value for MRSA pneumonia in populations with low MRSA pneumonia incidence. In cases of culture-negative pneumonia where initial empirical antibiotics include an MRSA-active agent, a negative MRSA PCR swab can be reasonably used to guide antibiotic de-escalation.

The ZEPHyR study: A randomized comparison of linezolid and vancomycin for MRSA pneumonia

BackgroundMethicillin-resistant Staphylococcus aureus (MRSA) accounts for 10–40% of hospital-acquired pneumonia, and even more in intensive care units. The current guidelines for the treatment of MRSA nosocomial pneumonia include vancomycin and linezolid. The authors of 2 prospective randomized trials comparing vancomycin and linezolid in nosocomial pneumonia had concluded to the non-inferiority of linezolid. A slight superiority of linezolid was observed in the MRSA pneumonia subgroup, in terms of clinical success and survival, but no definite conclusion could be drawn. MethodsA prospective randomized study was made to compare a fixed linezolid dose to dose-optimized vancomycin for the treatment of bacteriologically proven MRSA nosocomial pneumonia (ZEPHyR Study). ResultsAmong the 165 patients treated by linezolid (57.6%) in the PP population, 95 were clinically cured at the end of the study, compared to 81 of the 174 patients treated by vancomycin (46.6%) (IC 95% of the difference 0.5%–21.6%, P=0.042). Nephrotoxicity in the mITT population reached 8.4% in the linezolid group compared to 18.2% in the vancomycin group. ConclusionLNZ was superior to vancomycin for the treatment of MRSA nosocomial pneumonia.

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.

Prediction of methicillin-resistant Staphylococcus aureusin patients with non-nosocomial pneumonia

BackgroundMethicillin-resistant Staphylococcus aureus (MRSA) is recognized as an important cause of not only hospital acquired pneumonia, but also non-nosocomial pneumonia. However, the risk factors for non-nosocomial MRSA pneumonia are not clearly defined. Our objective was to identify risk factors at admission that were associated with non-nosocomial MRSA pneumonia.MethodsWe evaluated 943 patients admitted to a university-affiliated hospital with culture-positive bacterial pneumonia developed outside the hospital from January 2008 to December 2011. We compared the clinical characteristics between MRSA and non-MRSA pneumonia, and identified risk factors associated with MRSA pneumonia.ResultsOf 943 patients, MRSA was identified in 78 (8.2%). Higher mortality was observed in MRSA than in non-MRSA patients (33.3% vs. 21.5%; P = 0.017). In a logistic regression analysis, MRSA pneumonia was observed more frequently in patients with a previous history of MRSA infection (OR = 6.05; P < 0.001), a PSI score ≥120 (OR = 2.40; P = 0.015), intravenous antibiotic treatment within 30 days of pneumonia (OR = 2.23; P = 0.018). By contrast, non-MRSA pneumonia was observed more often in patients with a single infiltrate on chest radiography (OR = 0.55; P = 0.029).ConclusionsAnti-MRSA antibiotics could be considered in hospitalized non-nosocomial patients with several risk factors identified herein. The presence or absence of these factors would provide useful guidance in selecting initial empirical antibiotics.

Transcriptional Events during the Recovery from MRSA Lung Infection: A Mouse Pneumonia Model

Community associated methicillin-resistant Staphylococcus aureus (CA-MRSA) is an emerging threat to human health throughout the world. Rodent MRSA pneumonia models mainly focus on the early innate immune responses to MRSA lung infection. However, the molecular pattern and mechanisms of recovery from MRSA lung infection are largely unknown. In this study, a sublethal mouse MRSA pneumonia model was employed to investigate late events during the recovery from MRSA lung infection. We compared lung bacterial clearance, bronchoalveolar lavage fluid (BALF) characterization, lung histology, lung cell proliferation, lung vascular permeability and lung gene expression profiling between days 1 and 3 post MRSA lung infection. Compared to day 1 post infection, bacterial colony counts, BALF total cell number and BALF protein concentration significantly decreased at day 3 post infection. Lung cDNA microarray analysis identified 47 significantly up-regulated and 35 down-regulated genes (p<0.01, 1.5 fold change [up and down]). The pattern of gene expression suggests that lung recovery is characterized by enhanced cell division, vascularization, wound healing and adjustment of host adaptive immune responses. Proliferation assay by PCNA staining further confirmed that at day 3 lungs have significantly higher cell proliferation than at day 1. Furthermore, at day 3 lungs displayed significantly lower levels of vascular permeability to albumin, compared to day 1. Collectively, this data helps us elucidate the molecular mechanisms of the recovery after MRSA lung infection.

Nasal MRSA screening for surgical patients: predictive value for postoperative infections caused by MRSA

Postoperative methicillin-resistant Staphylococcus aureus (MRSA) infections are occasionally fatal. We hypothesized that nasal MRSA screening might predict the risk of postoperative MRSA infections. The aim of the current study was to elucidate the relationship between the positivity of nasal MRSA screening and postoperative MRSA infections. Six hundred and fourteen surgical patients who were admitted to the intensive care unit and underwent nasal MRSA screening between April 2006 and March 2011 were divided into MRSA-positive and -negative groups. The incidence of postoperative MRSA infections in the MRSA-positive and MRSA-negative groups were compared, and various risk factors for MRSA infections were evaluated. The incidence of postoperative MRSA infections, such as pneumonia and enteritis, in the MRSA-positive group was significantly higher than that in the MRSA-negative group (41.9 vs. 3.1 %). The significant independent risk factors for postoperative MRSA infections were a positive MRSA screening, an operation lasting more than 300 min and an emergency operation. A positive MRSA screening was the most statistically significant risk factor for postoperative MRSA pneumonia and enteritis, but was not a risk factor for MRSA surgical site infections. Nasal MRSA screening can help to identify patients who have an increased risk of developing postoperative MRSA infections, and would enable physicians to take a prompt action if these complications occur.

Improving Outcomes of Ventilator-Associated Pneumonia

Nosocomial pneumonia, especially ventilator-associated pneumonia (VAP), is a major cause of morbidity and mortality in the intensive care unit (ICU). This article discusses updates on bacterial resistance relevant to VAP, with a focus on methicillin-resistant Staphylococcus aureus (MRSA), treating MRSA pneumonia in the ICU, the use of tigecycline and doripenem for hospital-acquired pneumonia and VAP, and the potential utility of inhaled antibiotics as an alternative in the treatment of patients with VAP.

Linezolid Exerts Greater Bacterial Clearance but No Modification of Host Lung Gene Expression Profiling: A Mouse MRSA Pneumonia Model

BackgroundLinezolid (LZD) is beneficial to patients with MRSA pneumonia, but whether and how LZD influences global host lung immune responses at the mRNA level during MRSA-mediated pneumonia is still unknown.MethodsA lethal mouse model of MRSA pneumonia mediated by USA300 was employed to study the influence of LZD on survival, while the sublethal mouse model was used to examine the effect of LZD on bacterial clearance and lung gene expression during MRSA pneumonia. LZD (100mg/kg/day, IP) was given to C57Bl6 mice for three days. On Day 1 and Day 3 post infection, bronchoalveolar lavage fluid (BALF) protein concentration and levels of cytokines including IL6, TNFα, IL1β, Interferon-γ and IL17 were measured. In the sublethal model, left lungs were used to determine bacterial clearance and right lungs for whole-genome transcriptional profiling of lung immune responses.ResultsLZD therapy significantly improved survival and bacterial clearance. It also significantly decreased BALF protein concentration and levels of cytokines including IL6, IL1β, Interferon-γ and IL17. No significant gene expression changes in the mouse lungs were associated with LZD therapy.ConclusionLZD is beneficial to MRSA pneumonia, but it does not modulate host lung immune responses at the transcriptional level.

Risk factors for methicillin-resistant Staphylococcus aureus in patients with community-onset and hospital-onset pneumonia

The risk factors for methicillin-resistant Staphylococcus aureus (MRSA) pneumonia have not been fully characterized and are likely to be different depending on whether infection is acquired in the community or the hospital. We conducted a case-control study of 619 adults hospitalized between 2005 and 2010 with either MRSA or methicillin-sensitive S. aureus (MSSA) pneumonia. Patients with a respiratory culture within 48h of hospitalization had community-onset pneumonia whereas patients with a culture collected after this time point had hospital-onset pneumonia. Among patients with community-onset disease, the risk for MRSA was increased by tobacco use (OR 2.31, CI 1.23-4.31), chronic obstructive pulmonary disease (OR 3.76, CI 1.74-8.08), and recent antibiotic exposure (OR 4.87, CI 2.35-10.1) in multivariate analysis while patients with hospital-onset disease had an increased MRSA risk with tobacco use (OR 2.66, CI 1.38-5.14), illicit drug use (OR 3.52, CI 2.21-5.59), and recent antibiotic exposure (OR 2.04, CI 3.54-13.01). Hospitalization within the prior three months was associated with decreased risk (OR 0.64, CI 0.46-0.89) in multivariate analysis. This study suggests there are common and distinct risk factors for MRSA pneumonia based on location of onset. The decreased risk for MRSA pneumonia associated with recent hospitalization is unexpected and warrants further investigation. This case-control study showed that there are common and distinct risk factors associated with MRSA pneumonia depending on whether the infection onset is in the hospital or in the community. Recent hospitalization was unexpectedly shown to be associated with decreased risk for MRSA pneumonia and warrants further investigation.

Comparative Antimicrobial Effect of Vancomycin Serum Trough Level and AUC24/MIC in Patients with MRSA Pneumonia

Comparative Antimicrobial Effect of Vancomycin Serum Trough Level and AUC24/MIC in Patients with MRSA Pneumonia

Addition of Rifampin to Vancomycin for Methicillin-Resistant Staphylococcus aureus Infections: What Is the Evidence?

To evaluate evidence supporting efficacy and safety of the combination of vancomycin and rifampin for treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections. MEDLINE (1946-February 2013), EMBASE (1974-February 2013) and Cochrane Database of Systematic Reviews were searched. All human prospective trials and retrospective studies evaluating clinical outcomes of vancomycin-rifampin combinations were included. Case reports, case series, and in vitro or animal data were excluded. Full-text articles were included and abstracts excluded; 43 of 421 references were reviewed. Five articles met inclusion and were evaluated. A nonrandomized prospective trial reported complete clearance of MRSA bacteremia at 24 hours in all 14 burn patients receiving vancomycin-rifampin therapy. In a case-control study of 42 patients with MRSA endocarditis, adding rifampin prolonged bacteremia (5.2 vs 2.1 days, p < 0.001), decreased survival rates (79% vs 95%, p = 0.048), resulted in drug interactions (52% of cases), and increased hepatic transaminases (21% vs 2%, p = 0.014). In a retrospective analysis of 28 patients with persistent MRSA bacteremia requiring salvage therapy, switching from vancomycin-based to linezolid-based treatment was associated with better salvage success than adding rifampin (88% vs 0%, p < 0.001). In a randomized open-label trial of 42 patients with MRSA endocarditis, addition of rifampin to vancomycin did not affect cure rates (90% combination vs 82% monotherapy, p > 0.20), but increased duration of bacteremia (9 vs 7 days, p > 0.20) compared with vancomycin monotherapy. Another randomized open-label trial of combination versus monotherapy for MRSA pneumonia in 93 intensive care unit patients reported higher clinical successes (53.7% vs 31.0%, p = 0.047), similar 30-day mortality rates, and more adverse events with combination therapy (11 vs 6). Limited evidence exists to support the adjunctive use of rifampin to treat MRSA infections. The combination may increase drug interactions, adverse effects, and rifampin resistance. Further studies are needed to define the role of rifampin adjunct therapy.

Subtherapeutic Linezolid Concentrations in a Patient with Morbid Obesity and Methicillin-Resistant Staphylococcus aureus Pneumonia: Case Report and Review of the Literature

To report a case of subtherapeutic linezolid concentrations in a patient with morbid obesity. A 34-year-old male with morbid obesity (265 kg, body mass index 82 kg/m(2)) was admitted for severe sepsis due to respiratory failure requiring emergent intubation and treatment of community-acquired pneumonia. Admission tracheal aspirate culture revealed methicillin-resistant Staphylococcus aureus (MRSA) for which vancomycin was prescribed. Therapy subsequently was changed to linezolid, because the patient's clinical status worsened, with significant hypoxia (partial pressure of arterial oxygen/fraction of inspired oxygen [PaO2/FiO2] ratio 145), increasing leukocytosis (white blood cell count from 10,800/μL on admission to 15,400/μL on hospital day 6), and persistent fever (38.3 °C). After 48 hours of linezolid monotherapy, the patient remained febrile with continued leukocytosis, worsening hypoxemia, and a persistently positive MRSA culture from a repeat endotracheal aspirate. Linezolid serum concentrations were obtained and vancomycin was reinstituted, after which the patient began to improve (afebrile, improving PaO2/FiO2 ratio, decreasing leukocytosis). On hospital day 12, the patient removed his endotracheal tube, and a sputum sample was obtained for culture. The patient's clinical status subsequently declined, prompting addition of cefepime to his antibiotic regimen. This sputum culture revealed not only MRSA, but also quinolone-resistant Escherichia coli. After completing treatment for both organisms the patient was discharged home. Limited data on linezolid dosing in the morbidly obese population show lower serum drug concentrations than those in nonobese patients, but no clinical failure has been reported when treating MRSA skin and soft tissue infections or MRSA tracheitis. In our patient, low steady-state linezolid serum concentrations (peak 4.13 μg/mL [reference 15-27] and trough 1.27 μg/mL [reference 2-9]) were thought to contribute to his poor clinical response. To our knowledge, this is the first report of subtherapeutic linezolid concentrations correlated with decreased clinical effectiveness when during treatment of MRSA pneumonia in a patient with morbid obesity.

Macrophage destruction and loss of immunoregulatory function contributes to the pathology associated with MRSA pneumonia

Methicillin‐resistant Staphylococcus aureus (MRSA) USA300 produce numerous toxins that lyse specific population of leukocytes, including macrophages. We hypothesized that MRSA leads to immune dysregulation due to macrophage killing. We quantified macrophage gene products by qRT‐PCR and cytokine array after a 4‐hour exposure to MRSA USA300. THP‐1 cells significantly upregulated pro‐inflammatory cytokines including IL‐1β, IL‐1α, IL‐12 and MIP‐1α 4 hours after exposure to MRSA (≥2 fold each). Anti‐inflammatory cytokines IL‐27 (over 100‐fold, P&lt;0.01) and IL‐10 (over 10‐fold, P&lt;0.01) were induced 24 hours post‐MRSA infection. The cytotoxicity induced by MRSA was measured by LDH assay, cell viability by propidium iodide staining and flow cytometry analysis. Low dose (MOI 10) MRSA killed 35% of THP‐1 cells after 2 hours and over 70% after 4 hours. Macrophage cell death was not associated with annexin‐V staining, but was caspase‐dependent, as Z‐VAD‐FMK, a pan‐caspase inhibitor, significantly reduced THP‐1 cells’ cytotoxicity (40% reduction; P&lt;0.001). A α‐hemolysin null mutant of MRSA USA300 killed significantly less macrophages than wild‐type MRSA (19% vs 28%; P&lt;0.01), consistent with the role of Hla in activating the NLRC3 inflammasome. These results suggest the leukocidal activity of MRSA targeting macrophages can result in loss of their immunoregulatory activity.

Innate Stat3-mediated induction of the antimicrobial protein Reg3γ is required for host defense against MRSA pneumonia

Pulmonary Staphylococcus aureus (SA) infections are a public health concern and a major complication of hyper-IgE syndrome, caused by mutations in STAT3. In contrast to previous findings of skin infection, we observed that clearance of SA from the lung did not require T, B, or NK cells but did require Stat3 activation. Immunohistochemistry showed robust Stat3 phosphorylation in the lung epithelium. We identified that a critical Stat3 target gene in lung epithelium is Reg3g (regenerating islet-derived 3 γ), a gene which is highly expressed in gastrointestinal epithelium but whose role in pulmonary host defense is uncharacterized. Stat3 regulated Reg3g transcription through direct binding at the Reg3g promoter region. Recombinant Reg3γ bound to SA and had both bacteriostatic and bactericidal activity in a dose-dependent fashion. Stat3 inhibition in vivo reduced Reg3g transcripts in the lung, and more importantly, recombinant Reg3γ rescued mice from defective SA clearance. These findings reveal an antibacterial function for lung epithelium through Stat3-mediated induction of Reg3γ.

Emergence of methicillin-resistant Staphylococcus aureus USA300 genotype as a major cause of late-onset nosocomial pneumonia in intensive care patients in the USA

To compare demographic and clinical characteristics, and methicillin-resistant Staphylococcus aureus (MRSA) strain characteristics, in patients with early-onset (EO) and late-onset (LO) MRSA nosocomial pneumonia. This was a retrospective analysis of data from a multicenter observational study of nosocomial pneumonia patients admitted between November 2008 and July 2010. Laboratory analyses performed on MRSA isolates included confirmation of antimicrobial susceptibility and heteroresistance to vancomycin, USA typing, staphylococcal cassette chromosome (SCC) mec typing, and detection of Panton-Valentine leukocidin (PVL) genes. We identified 134 patients; 42 (31%) had EO MRSA pneumonia and 92 (69%) had LO MRSA pneumonia. The patients in the LO group were more likely to have risk factors for multidrug-resistant pathogens (98% vs. 76%, p<0.001). The MRSA USA300 strain was found with equal frequency in the EO and LO groups. Likewise, both groups had similar frequencies of isolates exhibiting PVL and SCCmec type IV. Our findings provide further evidence of the continued migration of community-associated MRSA into the healthcare setting in the USA. MRSA USA300 genotype has emerged as a significant cause of LO nosocomial pneumonia in intensive care units. Appropriate anti-MRSA antimicrobial therapy should be considered for both EO and LO hospital-acquired pneumonia and ventilator-associated pneumonia.

Prevalence and clinical prognosis of heteroresistant vancomycin-intermediate Staphylococcus aureus in a tertiary care center in China

Background The emergence of heteroresistant vancomycin-intermediate Staphylococcus aureus (hVISA) is increasingly challenging the methods for detection in diagnostic microbiology laboratories. However, the report of hVISA is rare in China. This study summarizes the prevalence and clinical features associated with hVISA infections at our institution and the local impact they have on clinical outcome. Methods A total of 122 methicillin-resistant Staphylococcus aureus (MRSA) isolates which were of the causative pathogens were collected. One hundred and two patients for whom we had full information of MRSA pneumonia were included. Isolates of MRSA were collected using PCR to detect the mecA gene. Both Etest and macro Etest were performed to screen for hVISA. The Staphylococcal chromosome cassette mec (SCCmec) types were determined by multiplex PCR strategy. Logistic regression analysis was used to determine the risk factors. Results Among the 122 MRSA isolates collected, 25 (20.5%) strains were identified as hVISA. There were 119 (97.5%) SCCmec III isolates, two (1.6%) SCCmec II isolates, and one (0.8%) SCCmec V isolate. The 30-day mortality of MRSAhospital acquired pneumonia (HAP) was 37.3%, and 62.5% for hVISA-HAP. Vancomycin treatment was the independent risk factor of hVISA. Factors independently associated with 30-day mortality in all patients were acute physiology and Chronic Health Evaluation (APACHE) II score &gt;20, multiple lobe lesions, and creatinine clearance rate (CCR) &lt;15 ml/min. Conclusions The prevalence of hVISA is 20.5% at our institution. hVISA-HAP patients had a poor clinical outcome. Vancomycin treatment was the independent predictors for hVISA infection. Factors independently associated with 30-day mortality in all patients were APACHE II score &gt;20, multiple lobe lesions and CCR &lt;15 ml/min.

Linezolid versus teicoplanin for MRSA pneumonia: A meta-analysis

Objective To systematically review the effectiveness and safety of linezolid versus teicoplanin in patients with MRSA pneumonia. Methods Such databases as CBM, CNKI, WanFang Data, VIP, Science Direct, PubMed, Ovid, SciFinder, The Cochrane Library (Issue 3, 2013) and EMbase were electronically searched for published articles (randomized controlled trials or non-randomized prospective trials with comparable baseline between groups) at home and abroad on the clinical effectiveness and safety of linezolid versus teicoplanin in patients with MRSA pneumonia from January 2003 to March 2013. Using the Cochrane methods, two reviewers independently screened literature, extracted data, and assessed the methodological quality of included studies. Then, meta-analysis was performed using RevMan 5.2 software in clinical cure rates, clinical effective rates, microbiologic eradication rates, and adverse reaction incidences. Results Finally, 7 studies were included involving 637 patients. The results of meta-analysis were clinical effective rates (RR=1.17, 95%CI 1.04 to 1.32, P=0.009), clinical cure rates (RR=1.06, 95%CI 0.94 to 1.19, P=0.37), bacterial clearance rates (RR=1.32, 95%CI 1.03 to 1.68, P=0.03), and adverse events rates (RR=1.24, 95%CI 0.78 to 1.97, P=0.37). The results of Begg test and Egger test were not significant (P>0.05). Conclusion Current evidence shows that, in treating MRSA pneumonia, linezolid is better than teicoplanin in clinical effective rates and bacterial clearance rates. However, they are alike in clinical cure rates and bacterial clearance rates.

The Impact of Serum Vancomycin Levels and Minimum Inhibitory Concentrations of Methicillin‐Resistant Staphylococcus aureus on Mortality in Patients with Nosocomial Pneumonia

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. 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). 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. 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. 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.