Methicillin-resistant S. Aureus Pneumonia Research Articles

Methicillin-Resistant Staphylococcus aureus -Associated Diarrhea in a Critically Ill Burn Patient

Described in surgical patients after antibiotic use in the 1950s and 1960s, Staphylococcus aureus ( S. aureus ) enterocolitis is a rare form of nosocomial diarrhea. However, S. aureus is not routinely tested like Clostridium difficile ( C. difficile ). We report a case of methicillin-resistant S. aureus (MRSA) enterocolitis found on stool culture in a 22-week pregnant female with a previously negative nasal MRSA culture, and a total burn surface area greater than 60%. She also developed necrotizing MRSA pneumonia and bacteremia. After starting broad-spectrum antibiotic for the necrotizing pneumonia with subsequent acute respiratory distress syndrome, the patient exhibited large voluminous diarrhea that tested positive for MRSA and negative for C. difficile in the stool culture. Similar to other reports of high-volume diarrhea, the diarrhea resolved quickly with enteral vancomycin. S. aureus should be considered along with C. difficile during the workup of nosocomial diarrhea, especially with exposure to broad-spectrum antibiotics in the critically ill patient. J Med Cases. 2021;12(7):257-261 doi: https://doi.org/10.14740/jmc3690

Dysfunctional accessory gene regulator (agr) as a prognostic factor in invasive Staphylococcus aureus infection: a systematic review and meta-analysis

The accessory gene regulator (agr) locus of Staphylococcus aureus is a quorum-sensing virulence regulator. Although there are many studies concerning the effect of dysfunctional agr on the outcomes of S. aureus infection, there is no systematic review to date. We systematically searched for clinical studies reporting outcomes of invasive S. aureus infections and the proportion of dysfunctional agr among their causative strains, and we performed a meta-analysis to obtain estimates of the odds of outcomes of invasive S. aureus infection with dysfunctional versus functional agr. Of 289 articles identified by our research strategy, 20 studies were meta-analysed for crude analysis of the impact of dysfunctional agr on outcomes of invasive S. aureus infection. Dysfunctional agr was generally associated with unfavourable outcomes (OR 1.32, 95% CI 1.05–1.66), and the impact of dysfunctional agr on outcome was more prominent in invasive methicillin-resistant S. aureus (MRSA) infections (OR 1.54, CI 1.20–1.97). Nine studies were meta-analysed for the impact of dysfunctional agr on the 30-day mortality of invasive S. aureus infection. Invasive MRSA infection with dysfunctional agr exhibited higher 30-day mortality (OR 1.40, CI 1.03–1.90) than that with functional agr. On the other hand, invasive MSSA infection with dysfunctional agr exhibited lower 30-day mortality (OR 0.51, CI 0.27–0.95). In the post hoc subgroup analysis by the site of MRSA infection, dysfunctional agr was associated with higher 30-day mortality in MRSA pneumonia (OR 2.48, CI 1.17–5.25). The effect of dysfunctional agr on the outcome of invasive S. aureus infection may vary depending on various conditions, such as oxacillin susceptibility and the site of infection. Dysfunctional agr was generally associated with unfavourable clinical outcomes and its effect was prominent in MRSA and pneumonia. Dysfunctional agr may be applicable for outcome prediction in cases of invasive MRSA infection with hardly eradicable foci such as pneumonia.

Survival during influenza-associated bacterial superinfection improves following viral- and bacterial-specific monoclonal antibody treatment.

Postinfluenza bacterial superinfections cause increased morbidity and mortality compared with singular infection with influenza during both pandemics and seasonal epidemics. Vaccines and current treatments provide limited benefit, a rationale to conduct studies utilizing alternative therapies. FY1 and an optimized version, MEDI8852, anti-influenza HA mAbs, have been shown to neutralize influenza virus during singular influenza infection. MEDI4893*, an anti-Staphylococcus aureus α-toxin mAb, has been shown to improve survival when administered prophylactically prior to S. aureus pneumonia. Our objective was to determine if mAbs can improve survival during postinfluenza bacterial pneumonia. We administered FY1 in a murine model of postinfluenza methicillin-resistant S. aureus (MRSA) pneumonia and observed improved survival rates when given early during the course of influenza infection. Our findings indicate decreased lung injury and increased uptake and binding of bacteria by macrophages in the mice that received FY1 earlier in the course of influenza infection, corresponding to decreased bacterial burden. We also observed improved survival when mice were treated with a combination of FY1 and MEDI4893* late during the course of postinfluenza MRSA pneumonia. In conclusion, both FY1 and MEDI4893* prolong survival when used in a murine model of postinfluenza MRSA pneumonia, suggesting pathogen-specific mAbs as a possible therapeutic in the context of bacterial superinfection.

Adhesion requirements of methicillin-resistant Staphylococcus aureus in bacterial pneumonia and influenza super-infection

Abstract In the respiratory tract, Staphylococcus aureus is associated with infections ranging from asymptomatic colonization to severe necrotizing pneumonia. While staphylococcal pneumonia has always been highly associated with influenza infections in young children and the elderly, it has emerged as the major cause of pneumonia associated with influenza since the 2009 H1N1 pandemic. Despite the clinical relevance of methicillin-resistant S. aureus (MRSA), few studies have examined bacterial factors of MRSA in pneumonia and how preceding influenza may alter the behavior of MRSA in the lung. Successful establishment of infection by bacterial pathogens requires adhesion to host cells. Staphylococcal species express a broad range of surface proteins that are involved in adhesion to host cells, known as the MSCRAMM family. MSCRAMM proteins have known roles in upper respiratory tract colonization, however their role in the lung is unknown. Preliminary data suggest that the MSCRAMM family members are important within the lung as MRSA lacking all MSCRAMMs (ΔsrtA) has decreased immune infiltrate in influenza super-infection. Additionally, the MSCRAMM family member SdrD has a role in both bacterial adherence as well as epithelial integrity and immunity in MRSA pneumonia and super-infection. Mice infected with MRSA lacking SdrD (ΔsdrD) have lower bacterial burden and increased expression of epithelial antimicrobial peptides cathelicidin and Reg3g with no difference in overall inflammation measured by immune infiltrate and pro-inflammatory cytokine levels. This suggests that MSCRAMM family members play a role in infection within the lung in both MRSA pneumonia and super-infection and can alter the immune response.

Methicillin-Resistant Staphylococcus aureus: A Pharmacotherapy Primer

Methicillin-Resistant Staphylococcus aureus: A Pharmacotherapy Primer

Prevalence of and outcomes from Staphylococcus aureus pneumonia among hospitalized patients in the United States, 2009-2012.

The burden of Staphylococcus aureus pneumonia is unknown despite being a major cause of mortality. We investigated national estimates of methicillin-resistant S aureus (MRSA) and methicillin-susceptible S aureus (MSSA) pneumonias and predictors of in-hospital mortality and hospital length of stay (LOS). This was a retrospective analysis of the National Inpatient Sample from 2009-2012. Adult patients with an ICD-9-CM primary diagnosis code for MRSA or MSSA pneumonia were included. Data weights were used to derive national estimates. Prevalence rates were reported per 100,000 hospital discharges, with trends presented descriptively. There were 104,562 patients who had a primary diagnosis of S aureus pneumonia, with 81,275 from MRSA. MRSA pneumonia prevalence decreased steadily from 2009 (75.6 cases per 100,000 discharges) to 2012 (56.6 cases per 100,000 discharges), with MSSA pneumonia experiencing a slight decrease. Mortality rates decreased between 2009 and 2012 for MRSA pneumonia (7.9% to 6.4%) and MSSA pneumonia (6.9% to 4.7%; P = .008). LOS was higher for MRSA (6.9-7.8 days) compared with MSSA (6.1-6.4 days). The prevalence of MRSA pneumonia has decreased among hospitalized adults in the United States in recent years accompanied by improvements in mortality and LOS. Although the prevalence of MRSA pneumonia is declining, national vigilance is still warranted.

Staphylococcus aureus bacteremic pneumonia.

Staphylococcus aureus bacteremic pneumonia is an uncommon cause of hospitalization, with a high mortality rate. However, published reports are scarce and have included a small number of cases. All patients with S. aureus bacteremic pneumonia were prospectively collected in our institution from 2000 to 2014, and a retrospective revision was performed to identify risk factors associated with methicillin resistance and to update the mortality of this entity. A total of 98 patients were admitted: 57.1% were due to methicillin-susceptible S. aureus (MSSA) and 42.8% due to methicillin-resistant S. aureus (MRSA). In 40 patients (40.8%), the infection was community acquired. Thirteen were ventilator-associated pneumonia episodes. The most frequent comorbidities were chronic lung disease (34.7%), chronic renal failure (31.6%), diabetes mellitus (29.6%), and cardiovascular disease (31.6%). Septic shock was present in 46 patients (46.9%). The 30-day mortality was 46.9%. MRSA infections occurred in older patients, more frequently with cardiovascular diseases, and they had received antibiotic treatment in the previous month more often than MSSA-infected patients. Patients with infection due to MSSA presented more frequently with septic shock, but they received more frequently appropriate empirical antibiotic therapy than patients with MRSA pneumonia (96% vs. 38.1%), and no differences in mortality were observed between both groups. In conclusion, S. aureus bacteremic pneumonia is a severe infection that, nowadays, affects people with comorbidities and the mortality is still high.

Association between microbial characteristics and poor outcomes among patients with methicillin-resistant Staphylococcus aureus pneumonia: a retrospective cohort study.

BackgroundMethicillin-resistant S. aureus (MRSA) pneumonia is associated with poor clinical outcomes. This study examined the association between microbial characteristics and poor outcomes among patients with methicillin-resistant Staphylococcus aureus pneumonia.FindingsThis retrospective cohort study included 75 patients with MRSA pneumonia who were admitted to two large tertiary care medical centers during 2003–2010. Multivariable models were created using Cox proportional hazards regression and ordinal logistic regression to identify predictors of mortality or increased length of stay (LOS). None of the microbial characteristics (PFGE type, agr dysfunction, SCCmec type, and detection of PVL, ACME, and TSST-1) were significantly associated with 30-day mortality or post-infection hospital length of stay, after adjusting for gender, age, previous hospital admission within 12 months, previous MRSA infection or colonization, positive influenza test, Charlson Comorbidity Index score, and treatment (linezolid or vancomycin).ConclusionLarge prospective studies are needed to examine the impact of microbial characteristics on the risk of death and other adverse outcomes among patients with MRSA pneumonia.Electronic supplementary materialThe online version of this article (doi:10.1186/s13756-015-0092-1) contains supplementary material, which is available to authorized users.

English

The latest published Linezolid in the treatment of subjects with nosocomial pneumonia proven to be due to methicillin-resistant Staphylococcus aureus (ZEPhyR) trial was a phase IV, randomized, double-blind, multicenter, comparator-controlled study comparing the efficacy of fixed-dose linezolid to dose-optimized vancomycin in hospitalized adults for the treatment of methicillin-resistant S. aureus (MRSA) nosocomial pneumonia. They found out that the superiority of linezolid over vancomycin was with regard to both clinical responses and microbiological outcomes but without a survival advantage. However, the study had a number of shortcomings: failing to implement the guideline about vancomycin doing and goal trough level, recruitment of health care-associated pneumonia (HCAP) population, failing to explain mortality rate in different minimal inhibitory concentration (MIC) subgroups and glomerular filtration rates (GFR) subgroups etc. Limitations of the study made us consider routine use of linezolid for the treatment of MRSA pneumonia with prudence. Key words: Nosocomial pneumonia (NP), trough level, ventilator-associated pneumonia (VAP), health care-associated pneumonia (HCAP), methicillin-resistant S. aureus (MRSA).

Timing of post-influenza bacterial superinfection with MRSA dictates the outcome of MRSA pneumonia in mice (P4027)

Abstract Secondary bacterial pneumonias caused by S. aureus, S. pneumoniae and H. influenzae are a common occurrence following influenza infection and are responsible for significant morbidity and mortality worldwide. Others have shown in murine models that 5-8 days after influenza challenge the susceptibility to secondary bacterial infections increases; though the mechanism of this increased susceptibility is still elusive. Here, we report that 2-3 days after influenza challenge (before the onset of clinical symptoms, i.e. body weight loss) mice actually have increased resistance to secondary infection with methicillin resistant S. aureus (MRSA). Importantly, despite this early protection from MRSA, the response to bacteria early in the influenza infection results in increased viral growth and subsequently death of mice. The mechanism of this increased resistance to secondary MRSA pneumonia early after influenza is dependent on the transient presence of IL-13 and on type I IFN signaling, as mice deficient in these cytokine or cytokine receptor do not show increased resistance to secondary MRSA pneumonia 2-3 days after influenza infection, and injection of exogenous IL-13 to mice co-infected with MRSA pneumonia on day 7 increases resistance to bacteria. Thus, depending on the time of secondary infection in relation to influenza, the disease phenotype contracted by mice is greatly different, awareness of which is important for the design of rational treatments in clinics.

Characteristics of Drug-Susceptible and Drug-Resistant Staphylococcus aureus Pneumonia in Patients with HIV

ObjectivesTo examine predictors and outcomes of Staphylococcus aureus Pneumonia (SAP) in people with HIV compared with Streptococcus pneumoniae Pneumonia (SPP), and to compare Methicillin-Resistant S. aureus (MRSA) with Methicillin-Sensitive S. aureus (MSSA) pneumonias in this population.MethodsWe conducted a retrospective case-control study of HIV-infected patients admitted to a single center with culture-proven S. aureus or S. pneumoniae pneumonia. We identified patients through a computerized database, conducted structured chart reviews, and performed bivariate and multivariate analyses using logistic regression.ResultsWe compared 47 SAP episodes in 42 patients with 100 SPP episodes in 93 patients. Use of any antibiotics prior to admission (OR=3.5, p=0.02), a co-morbid illness (OR=4.2, p=0.04), and recent healthcare contact (OR=12.0, p<0.001) were significant independent predictors of SAP. Patients with SAP were more likely to require intensive care (OR=2.7, p=0.02) and mechanical ventilation (OR=3.1, p=0.02), but not to die. MRSA was more common (57% of cases) than MSSA, but outcomes were not significantly worse.ConclusionsPatients with HIV and SAP have worse outcomes than those with SPP. Clinicians should consider empiric antibiotic coverage for MRSA in patients admitted with HIV and pneumonia, given the high prevalence of MRSA. Further studies are warranted to examine morbidity differences between HIV-associated MSSA and MRSA pneumonia.

Health-Care-Associated Pneumonia

Health-Care-Associated Pneumonia

Recent advances in the treatment of infections due to resistant Staphylococcus aureus

This paper reviews recent data on the treatment of infections caused by drug-resistant Staphylococcus aureus, particularly methicillin-resistant S. aureus (MRSA). This review will focus on new findings reported in the English-language medical literature from June 2003 to September 2004. Despite the emergence of resistant and multidrug-resistant S. aureus, we have three effective drugs in clinical use for which little resistance has been observed: quinupristin-dalfopristin, linezolid, and daptomycin. Linezolid looks particularly promising in the treatment of MRSA pneumonia. Daptomycin displays rapid bactericidal activity in vitro, but, so far, clinical trials have only been conducted for the treatment of skin and soft-tissue infections. There are three drugs with broad-spectrum activity against Gram-positive organisms at an advanced stage of testing: two new glycopeptides with potent bacteriocidal activity and long half-lives (oritavancin and dalbavancin), and tigecycline, a minocycline derivative. These drugs have also shown efficacy in the treatment of skin and soft-tissue infections. The promising data that have emerged in the last year indicate that we may have six available drugs to treat resistant S. aureus infections within the next few years. The next goal is to determine the appropriate indications and cost-effectiveness of each of these drugs in our treatment strategy against S. aureus and other Gram-positive pathogens.