Clinical and bacterial characteristics of Pseudomonas aeruginosa affecting the outcome of patients with bacteraemic pneumonia.

Few studies have assessed the clinical and bacterial characteristics of Pseudomonas aeruginosa (PA) bacteraemic pneumonia (BP) episodes. This study analysed all non-duplicate PA-BP episodes from a tertiary hospital in 2013-2017. Epidemiology, clinical data, antimicrobial therapy and outcomes were recorded. Whole-genome sequencing was performed on PA blood isolates. The impact on early and late overall mortality of host, antimicrobial treatment and pathogen factors was assessed by multivariate logistic regression analysis. Of 55 PA-BP episodes, 32 (58.2%) were caused by extensively drug-resistant (XDR) PA. ST175 (32.7%) and ST235 (25.5%) were the most frequent high-risk clones. ß-Lactamases/carbapenemases were detected in 29 isolates, including blaVIM-2 (27.2%) and blaGES type (25.5%) [blaGES-5 (20.0%), blaGES-1 (3.6%) and blaGES-20 (1.8%)]. The most prevalent O-antigen serotypes were O4 (34.5%) and O11 (30.9%). Overall, an extensive virulome was identified in all isolates. Early mortality (56.4%) was independently associated with severe neutropenia (aOR = 4.64, 95% CI 1.11-19.33; P = 0.035) and inappropriate empirical antimicrobial therapy (aOR = 5.71, 95% CI 1.41-22.98; P = 0.014). Additionally, late mortality (67.3%) was influenced by septic shock (aOR = 8.85, 95% CI 2.00-39.16; P = 0.004) and XDR phenotype (aOR = 5.46, 95% CI 1.25-23.85; P = 0.024). Moreover, specific genetic backgrounds [ST235, blaGES, gyrA (T83I), parC (S87L), exoU and O11 serotype] showed significant differences in patient outcomes. Our results confirm the high mortality associated with PA-BP. Besides relevant clinical characteristics and inappropriate empirical therapy, bacteria-specific genetics factors, such as XDR phenotype, adversely affect the outcome of PA-BP.

Lefamulin vs moxifloxacin for community-acquired bacterial pneumonia.

Lefamulin is a novel pleuromutilin antibiotic with potent in vitro activity against key community-acquired bacterial pneumonia (CABP) pathogens. However, the clinical efficacy and safety of lefamulin for treating CABP remains unclear.An integrated analysis of 2 phase III trials investigating the clinical efficacy and safety of lefamulin vs moxifloxacin in the treatment of CABP was conducted.A total of 1289 patients (lefamulin group: 646 and moxifloxacin group: 643) were included in this analysis. The early clinical response rate was 89.3% and 90.5% among lefamulin and moxifloxacin group, respectively. Lefamulin was noninferior to moxifloxacin (89.3% vs 90.5%, RR: 0.99, 95% CI: 0.95-1.02, I = 0%). In terms of clinical response at test of cure, no significant difference was observed between the lefamulin and moxifloxacin groups (for modified intention to treat population, RR: 0.98, 95% CI: 0.94-1.02, I = 0%; for clinically evaluable population, RR: 0.96, 95% CI: 0.93-1.00, I = 0%). In the subgroup analysis, the early clinical response rate at early clinical assessment and clinical response rate at test of cure of lefamulin was similar to that of moxifloxacin across different subgpopulations and all baseline CABP pathogens. Lefamulin was associated with a similar risk of adverse events as moxifloxacin.Clinical efficacy and tolerability for lefamulin in the treatment of CABP were similar to those for moxifloxacin.

Immune memory induced by intranasal vaccination with a modified-live viral vaccine delivered to colostrum fed neonatal calves.

Bovine respiratory disease (BRD) remains a major health problem despite extensive use of vaccines during the post-weaning period. Apparent vaccine failure is attributed, in part, to primary vaccination during the period of greatest risk for BRD, providing inadequate time for onset of protective immunity. The current study investigated whether intranasal (IN) vaccination of 3-6 week old calves with a modified-live viral (MLV) vaccine induced sufficient immune memory to prevent respiratory disease and accelerate onset of protective immunity 5 months later. Vaccine groups included naïve controls, a single IN vaccination at 3-6 weeks of age, primary IN vaccination at 6 months, and either an IN or subcutaneous (SC) booster vaccination at 6 months (n = 10/group). All calves were challenged with BHV-1 four days after vaccination at 6 months of age. Primary IN vaccination at 6 months did not significantly reduce clinical disease but significantly (P < 0.01) reduced virus shedding. A single IN vaccination at 3-6 weeks of age significantly (P < 0.05) reduced weight loss but did not reduce fever or virus shedding. Both IN and SC booster vaccinations, significantly (P < 0.01) reduced clinical disease but virus shedding was significantly (P < 0.001) reduced only by IN booster vaccination. Reduction in virus shedding was significantly (P < 0.01) greater following booster versus primary IN vaccination at 6 months. All vaccination regimes significantly (P < 0.01) reduced secondary bacterial pneumonia and altered interferon responses relative to naïve controls. Only IN booster vaccination significantly (P < 0.05) increased BHV-1 specific IgA in nasal secretions. These results confirm primary MLV IN vaccination at 3 to 6 weeks of age, when virus neutralizing maternal antibody was present, induced immune memory with a 5 month duration. This immune memory supported rapid onset of protective immunity four days after an IN booster vaccination.

Ceftazidime-Avibactam as Salvage Therapy for Infections Caused by Enterobacteriales Coresistant to Carbapenems and Polymyxins.

In this article, we report a case series of patients with infections caused by Enterobacteriales coresistant to carbapenems and polymyxins who were treated with ceftazidime/avibactam (CAZ-AVI) salvage therapy on a compassionate-use protocol. We enrolled 29 adult patients in 3 centers that had an infection due to a resistant microorganism and for whom the treatments available were considered ineffective, treated them with CAZ-AVI, and assessed clinical and microbiological cure at the end of treatment and all-cause mortality at 14 days and 30 days. The antimicrobial susceptibility profile was determined using broth microdilution, and total genomic DNA was sequenced. Twelve (41.4%) patients had bacteremia, and 48.3% (14/29) of the infections were treated with combination therapy. All strains were producers of KPC-2 and were susceptible to CAZ-AVI (MIC90, 1 µg/ml). Clinical success was high (24/29 [82.7%; 95% confidence interval, 64.2 to 94.2%]), even for the bacteremic cases (75%). The 14-day and 30-day mortality rates were 9/29 (31%) and 15/29 (51.7%), respectively. The 14-day mortality rate for pneumonia was the same as that for bloodstream infections (33.3%) and although not significant, we found that patients with renal impairment that received adjusted doses of CAZ-AVI had high mortality (4/9 [44%]; P = 0.22). We concluded that CAZ-AVI is an option for the treatment of severe infections due to difficult-to-treat drug-resistant Enterobacteriales.

Antibiotic treatment adequacy and death among patients with Pseudomonas aeruginosa airway infection.

OBJECTIVE: The effect of antibiotics on survival in patients with pulmonary Pseudomonas aeruginosa is controversial. The aim of this study is to i) determine the prevalence of adequate antibiotic treatment of P. aeruginosa in an unselected group of adult non-cystic fibrosis patients and ii) to assess the overall mortality in study patients treated with adequate vs. non-adequate antibiotics. METHODS: Prospective, observational study of all adult patients with culture verified P. aeruginosa from 1 January 2010-31 December 2012 in Region Zealand, Denmark. Patients with cystic fibrosis were excluded. Adequate therapy was defined as any antibiotic treatment including at least one antipseudomonal beta-lactam for a duration of at least 10 days. Furthermore, P. aeruginosa had to be tested susceptible to the given antipseudomonal drug and treatment had to be approved by senior clinician to fulfil the adequate-criteria. RESULTS: A total of 250 patients were identified with pulmonary P. aeruginosa. The vast majority (80%) were treated with non-adequate antibiotic therapy. All-cause mortality rate after 12 months was 49% in adequate treatment group vs. 52% in non-adequate treatment group. Cox regression analysis adjusted for age, gender, bacteraemia, comorbidities and bronchiectasis showed no significant difference in mortality between treatment groups (adequate vs. non-adequate: hazard ratio 0.95, 95% CI 0.59-1.52, P = 0.82). CONCLUSION: Adequate antipseudomonal therapy was only provided in a minority of patients with pulmonary P. aeruginosa. Adequate therapy did not independently predict a favourable outcome. New research initiatives are needed to improve the prognosis of this vulnerable group of patients.

Acinetobacter Pneumonia: Improving Outcomes With Early Identification and Appropriate Therapy.

In an era of increasing antimicrobial resistance, Acinetobacter distinguishes itself as one of the most resistant Gram-negative bacteria responsible for significant morbidity and mortality. New solutions are needed to combat the detrimental effects of increasing rates of antimicrobial resistance. Using empiric broad-spectrum antibiotics in patients deemed at risk for infections caused by multidrug-resistant pathogens may protect against attributable mortality, but this temporary solution furthers the risk of antimicrobial resistance. In this article we will review relevant strategies to aid with early identification and appropriate treatment of Acinetobacter pneumonia while preserving antibiotic susceptibility.

Evaluation on clinical efficacy of Fuzheng Jiedu Huayu Decoction combined with antibiotics in the treatment of pneumonia in the elderly - A multi-center, double-blind, parallel, randomized controlled trial.

OBJECTIVE: To evaluate the efficacy and safety of Fuzheng Jiedu Huayu Decoction (FJHD) in treating pneumonia in the elderly. METHODS: Adopting a multi-center, double-blind, parallel, randomized controlled trial, 284 elderly pneumonia patients were enrolled and randomly allocated to the standard treatment with FJHD (treatment group, TG) and the standard treatment with placebo group (control group, CG). Efficacy and safety was evaluated through mortality rate, curative rate, symptom improvement, chest X-ray (CXR) lesion absorption, arterial blood gas (ABG), peripheral blood leukocyte count (PBLC) and adverse events. RESULTS: There was no significant difference in mortality rate between both groups (P > 0.05). TG significantly enhanced the curative rate of a 2-week treatment course (P < 0.05). Compared with CG, TG significantly decreased the expectoration score during the first and second week of treatment (P < 0.05). During the first week, improvement in expectoration was conducive to airway patency. During the second week, wheezing, shortness of breath and other symptoms were also significantly improved. During the third week, body temperature was stable. TG improved lesion absorption with Pneumonia Severity Index (PSI) class II (P < 0.05) and SMART-COP score 1 (P < 0.05). TG significantly decreased the arterial carbon dioxide partial pressure after a 1-week treatment. There were no serious adverse events in TG. CONCLUSION: Standard anti-infection treatment with FJHD is a safe and reliable method of treating elderly patients with pneumonia, improving the curative effect after a 2-week treatment course, ameliorating expectoration and promoting the absorption of pneumonia lesions.

Healthcare-Associated Pneumonia and Hospital-Acquired Pneumonia: Bacterial Aetiology, Antibiotic Resistance and Treatment Outcomes: A Study From North India.

BACKGROUND: Data regarding the comparative profiling of HCAP and HAP from developing countries like India are scant. We set out to address the microbial aetiology, antibiotic resistance and treatment outcomes in patients with HCAP and HAP. METHODS: 318 consenting patients with HCAP (n = 165, aged 16-90 years; median 60 years; 97 males) or HAP (n = 153; aged 16-85 years; median 45 years; 92 males) presenting to a tertiary care hospital in North India from 2013 to 2015 were prospectively recruited for the study. Data on patient characteristics, microbial aetiology, APACHE II scores, treatment outcomes and mortality were studied. Clinical outcomes were compared with various possible predictors employing logistic regression analysis. RESULTS: Patients in HCAP had more comorbidity. Escherichia coli (30, 18%) and Acinetobacter baumannii (62, 41%) were the most commonly isolated bacteria in HCAP and HAP, respectively. Multidrug-resistant bacteria were isolated more frequently in HCAP, only because the incidence of extensively drug-resistant bacteria was markedly high in HAP (p = 0.00). The mean APACHE II score was lower in HCAP (17.55 ± 6.406, range 30) compared to HAP (19.74 ± 8.843, range 37; p = 0.013). The length of stay ≥ 5 days (p = 0.036) and in-hospital mortality was higher in HAP group (p = 0.002). The most reliable predictors of in-hospital mortality in HCAP and HAP were APACHE II score ≥ 17 (OR = 14, p = 0.00; HAP: OR = 10.8, p = 0.00), and septic shock (OR = 4.5, p = 0.00; HAP: OR = 6.9, p = 0.00). CONCLUSION: The patient characteristics in HCAP, treatment outcomes, bacterial aetiology, and a higher incidence of antibiotic-resistant bacteria, suggest that HCAP although not as severe as HAP, can be grouped as a separate third entity.

Cytosolic Phospholipase A2α Promotes Pulmonary Inflammation and Systemic Disease during Streptococcus pneumoniae Infection.

Pulmonary infection by Streptococcus pneumoniae is characterized by a robust alveolar infiltration of neutrophils (polymorphonuclear cells [PMNs]) that can promote systemic spread of the infection if not resolved. We previously showed that 12-lipoxygenase (12-LOX), which is required to generate the PMN chemoattractant hepoxilin A3 (HXA3) from arachidonic acid (AA), promotes acute pulmonary inflammation and systemic infection after lung challenge with S. pneumoniae As phospholipase A2 (PLA2) promotes the release of AA, we investigated the role of PLA2 in local and systemic disease during S. pneumoniae infection. The group IVA cytosolic isoform of PLA2 (cPLA2α) was activated upon S. pneumoniae infection of cultured lung epithelial cells and was critical for AA release from membrane phospholipids. Pharmacological inhibition of this enzyme blocked S. pneumoniae-induced PMN transepithelial migration in vitro Genetic ablation of the cPLA2 isoform cPLA2α dramatically reduced lung inflammation in mice upon high-dose pulmonary challenge with S. pneumoniae The cPLA2α-deficient mice also suffered no bacteremia and survived a pulmonary challenge that was lethal to wild-type mice. Our data suggest that cPLA2α plays a crucial role in eliciting pulmonary inflammation during pneumococcal infection and is required for lethal systemic infection following S. pneumoniae lung challenge.

Efficacy of High-Dose Meropenem (Six Grams per Day) in Treatment of Experimental Murine Pneumonia Induced by Meropenem-Resistant Pseudomonas aeruginosa.

High-dose meropenem (MEPM; 6 g/day) has been approved as a treatment for purulent meningitis; however, little is known regarding its in vivo efficacy in refractory lower respiratory tract infections. The purpose of this study was to evaluate the efficacy of MEPM at 6 g/day in a murine model of severe pneumonia caused by MEPM-resistant Pseudomonas aeruginosa Experimental pneumonia induced by MEPM-resistant P. aeruginosa was treated with normal-dose MEPM (150 mg/kg of body weight, simulating a 3-g/day regimen in humans) or high-dose MEPM (500 mg/kg, simulating a 6-g/day regimen in humans). Mice treated with high-dose MEPM showed significantly restored survival relative to that of untreated mice and tended to show a survival rate higher than that of mice treated with normal-dose MEPM. The viable bacterial counts (of two clinical isolates) in the lungs decreased significantly in mice treated with high-dose MEPM from those for untreated mice (P < 0.001) or mice treated with normal-dose MEPM (P, <0.01 and <0.05). The number of inflammatory cells in the bronchoalveolar lavage fluid (BALF) was also significantly lower in mice treated with high-dose MEPM than in untreated mice. The free MEPM concentration in the epithelial lining fluid (ELF) exceeded 16 µg/ml for 85 min in mice treated with high-dose MEPM, but not for mice treated with normal-dose MEPM. Our results demonstrate that high-dose MEPM (6 g/day) might provide better protection against pneumonia caused by MEPM-resistant strains of P. aeruginosa than the dose normally administered (less than 3 g/day).

Salvage Therapy with Ceftolozane-Tazobactam for Multidrug-Resistant Pseudomonas aeruginosa Infections.

Infections caused by multidrug-resistant Pseudomonas aeruginosa (MDRPA) present a major problem for therapeutic management. We report here our experience with 12 patients with a severe MDRPA infection (6 of which were pneumonia) who received salvage therapy with ceftolozane-tazobactam after inappropriate empirical treatment and/or suboptimal targeted treatment. Although 10 of the 12 patients (83.3%) experienced septic shock, only 3 patients (25%) died during the follow-up period. Microbiological cure in 7 patients (58.3%) was observed.

Clinical characteristics of nursing home-acquired pneumonia in elderly patients admitted to a Korean teaching hospital.

BACKGROUND/AIMS: Nursing home-acquired pneumonia (NHAP) is included under healthcare-associated pneumonia. However, the optimal treatment strategy for NHAP has been controversial in several studies. We evaluated the clinical features of NHAP compared to community-acquired pneumonia (CAP) in elderly patients admitted with pneumonia. METHODS: This was a retrospective study in elderly patients aged ≥ 65 years with NHAP or CAP who were hospitalized at Jeju National University Hospital between January 2012 and April 2013. RESULTS: A total of 209 patients were enrolled, and 58 (27.7%) had NHAP. The patients with NHAP were older, had more frequent central nervous system disorders, and showed worse clinical parameters. Potential drug-resistant pathogens were more frequently detected in the NHAP group (22.4% vs. 9.9%, p = 0.018), and the incidences of Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus were 8.6% and 10.3%, respectively. In-hospital mortality occurred in 13 patients (22.4%) with NHAP and 17 patients (11.2%) with CAP (p = 0.039). In multivariate analyses, only higher pneumonia severity index (PSI) score was associated with increased mortality (p < 0.001), and the PSI score was higher in the NHAP group than that in the CAP group. CONCLUSIONS: Elderly patients admitted with NHAP showed more severe pneumonia at onset, higher rates of potentially drug-resistant pathogens, and worse clinical outcomes than those with CAP. However, higher in-hospital mortality in those with NHAP seemed to be related to the PSI score reflecting host factors and severity of pneumonia rather than the type of pneumonia or the presence of drug-resistant pathogens.

Risk of developing pneumonia is enhanced by the combined traits of fluoroquinolone resistance and type III secretion virulence in respiratory isolates of Pseudomonas aeruginosa.

OBJECTIVES: To determine the differential association of host characteristics, antimicrobial resistance, and type III secretion system virulence of Pseudomonas aeruginosa isolates with respiratory syndromes in hospitalized adult patients. DESIGN: Retrospective, cohort study. SETTING: Community teaching hospital. PATIENTS: Two hundred eighteen consecutive adult patients with respiratory culture positive for P. aeruginosa between January 2005 to January 2010. INTERVENTIONS: Medical charts were reviewed to obtain demographic, laboratory, radiographic, and clinical information. Isolates were assayed by polymerase chain reaction for genes encoding the type III secretion system effectors (ExoU, ExoS, and PcrV) and for strain relatedness using randomly amplified polymorphic DNA analysis. Levofloxacin susceptibility was determined by broth microdilution. Patients were grouped by colonization, bronchitis, or pneumonia and were compared for differential risk of developing the clinical syndrome with respect to host and microbial characteristics. MEASUREMENTS AND MAIN RESULTS: Half of the study cohort (54%, 117 of 218) had pneumonia, 32% (70 of 218) had bronchitis, and 14% (31 of 218) had colonization; in-hospital mortality was 35%, 11%, and 0%, respectively. Host factors strongly associated with pneumonia development were residence in long-term care facility, healthcare-associated acquisition of P. aeruginosa, higher Acute Physiology and Chronic Health Evaluation II score, presence of enteral feeding tube, mechanical ventilation, and recent history of pneumonia. Fluoroquinolone-resistant (57% vs 34%, 16%; p < 0.0001) and multidrug-resistant (36% vs 26%, 7%; p = 0.0045) strains were more likely to cause pneumonia than bronchitis or colonization, respectively. Analysis of host and microbial factors in a multivariate regression model yielded the combined traits of fluoroquinolone resistance and gene encoding the type III secretion system ExoU effector in P. aeruginosa as the single most significant predictor of pneumonia development. CONCLUSIONS: These results suggest that fluoroquinolone-resistant phenotype in a type III secretion system exoU strain background contributes toward the pathogenesis of P. aeruginosa in pneumonia.

The therapeutic effect of tigecycline, unlike that of Ceftazidime, is not influenced by whether the Klebsiella pneumoniae strain produces extended-spectrum ß-lactamases in experimental pneumonia in rats.

The efficacies of tigecycline and ceftazidime against fatal pneumonia in rats caused by an extended-spectrum ß-lactamase (ESBL)-positive Klebsiella pneumoniae strain or its wild-type (WT) progenitor were compared. Ceftazidime at 12.5 or 50 mg/kg of body weight twice daily (b.i.d.) was effective (50% or 100% rat survival) in pneumonia caused by the WT isolate but unsuccessful (100% rat mortality) in pneumonia caused by the ESBL-positive variant. In contrast, tigecycline at 6.25, 12.5, or 25 mg/kg b.i.d. showed dosage-dependent efficacy up to 100% rat survival irrespective of the ESBL character of the infecting organism.

Mortality following nursing home-acquired lower respiratory infection: LRI severity, antibiotic treatment, and water intake.

OBJECTIVE: In some nursing home populations, antibiotic treatment may not reduce mortality following lower respiratory infection (LRI). To better inform treatment decisions, we determined influences on mortality following LRI among antibiotic-treated and non-antibiotic-treated residents in 2 populations. DESIGN: Observational, prospective, cohort studies. SETTING: Ninety-seven nursing homes (36 US, 61 Netherlands). PARTICIPANTS: Residents (1044 US, 513 Netherlands) who met a standardized study definition for LRI. MEASUREMENTS: Demographics, symptoms and physical findings of LRI, functional status, major illness diagnoses, dementia status, treatments, and date of death within 6 months after diagnosis. METHODS: We estimated a 2-period (0-14/15-90 days) weighted proportional hazards model of mortality for antibiotic-treated (n = 1280) and non-antibiotic-treated (n = 277) residents; both weights and regressors provide "doubly robust" risk adjustment-for LRI (illness) severity using a prognostic score and for nonrandom receipt of antibiotic treatment using a propensity score. RESULTS: In both the United States and the Netherlands, 14-day mortality was associated with three factors-LRI severity, water intake at diagnosis, and antibiotic use (not directly by severe dementia)-that accounted for 82% or, sequentially, 39%, 42%, and 1% of the cross-national mortality difference. The LRI Severity Score (based only on at-diagnosis eating dependency, pulse rate, decreased alertness, and breathing difficulty, with adequate discrimination [c ≥ 0.74] and calibration, and cross-indexed to commonly used LRI mortality measures) was related to mortality through 90 days, regardless of treatment. With sufficient water intake at diagnosis, 14-day mortality was unrelated to not receiving antibiotic treatment (adjusted hazard ratio [AHR], 1.20; 95% confidence interval, 0.70-2.04); insufficient water intake was related to increased 14-day mortality with antibiotics (AHR, 1.90; 1.38-2.60) or without (AHR, 7.12; 4.83-10.5). After 14 days, relative mortality worsened for antibiotic-treated residents with insufficient water intake. Inadequate water intake was related to increased eating dependence at onset of the LRI (OR, 4.2; 3.0-5.8). CONCLUSION: LRI severity, water intake, and antibiotic use explain mortality in both studies and reconcile cross-study Dutch/US 14-day mortality differences. LRI severity, derived at 14 days, is related to mortality through 90 days, regardless of treatment, and is key to risk adjustment. With adequate hydration, the survival benefit from antibiotic use is nonsignificant. Conversely, hydration, even without antibiotic treatment, appears central to curative treatment. In LRI guidelines, treatment, and research, the relative benefits of antibiotics and hydration for curative treatment should be addressed.

Guideline adherence and macrolides reduced mortality in outpatients with pneumonia.

BACKGROUND: For outpatients with pneumonia, guidelines recommend empiric antibiotics and some suggest macrolides are preferred agents. We hypothesized that both guideline-concordant antibiotics and macrolides would be associated with reduced mortality. METHODS: All outpatients with pneumonia assessed at 7 Emergency Departments in Edmonton, Alberta, Canada were enrolled in a population-based registry that included clinical-radiographic data, Pneumonia Severity Index (PSI) and treatments. Guideline-concordant regimens included macrolides and respiratory fluoroquinolones; other regimens were "discordant". Main outcome was 30-day all-cause mortality. RESULTS: The study included 2973 outpatients; mean age 51 years, 47% female, most had mild pneumonia (73% PSI Class I-II). Over 30-days, 38 (1%) patients died, 228 (8%) were hospitalized, and 253 (9%) reached the endpoint of death or hospitalization. Most (2845 [96%]) patients received guideline-concordant antibiotics. Compared to patients receiving discordant antibiotics, those receiving guideline-concordant antibiotics were less likely to die within 30-days (8 [6%] versus 30 [1%], adjusted OR 0.23, 95% CI 0.09-0.59, p = 0.002). Within the guideline-concordant subgroup, compared to the 947 (33%) patients treated with fluoroquinolones, those receiving macrolides [1847 (64%)] were less likely to die (25 [3%] versus 4 [0.2%], adjusted OR 0.28, 95% CI 0.09-0.86, p = 0.03). CONCLUSIONS: In outpatients with pneumonia, treatment with guideline-concordant antibiotics and macrolides were both associated with mortality reduction.

Site of infection rather than vancomycin MIC predicts vancomycin treatment failure in methicillin-resistant Staphylococcus aureus bacteraemia.

BACKGROUND: Therapeutic use of vancomycin is characterized by decreased susceptibilities and increasing reports of clinical failures. Few studies have examined the clinical outcomes of patients with methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia treated with vancomycin. The primary objective was to compare clinical outcomes of patients with MRSA bacteraemia treated according to standard of care practices. METHODS: Patients were included if: (i) admitted to University of New Mexico Hospital between 2002 and 2009; (ii) ≥18 years of age; (iii) had one blood culture positive for MRSA; and (iv) received vancomycin. Clinical outcomes were defined as cure, failure (relapse of infection 30 days after completion of therapy, death or change in therapy) or unevaluable. Patient demographics, source of bacteraemia, treatment regimen, and microbiological characteristics were determined. RESULTS: Two hundred patients with MRSA bacteraemia were included. Sixty-one patients were unevaluable, leaving 139 patients for the final analysis. Seventy-two (51.8%) patients were cured and 67 (48.2%) experienced vancomycin failure. Vancomycin MIC(90) was 2 mg/L for both groups by Etest. Patients with endocarditis (P = 0.02) or pneumonia (P = 0.02) were more likely to fail therapy. Panton-Valentine leucocidin, loss of agr functionality and strain type were not predictors of outcomes in this study. CONCLUSIONS: High failure rates were observed in patients with MRSA bacteraemia treated with vancomycin, despite high vancomycin troughs and low rates of nephrotoxicity. Predictors of vancomycin failure included endocarditis and pneumonia. In these situations, vancomycin provides suboptimal therapy.

Moxifloxacin monotherapy versus ß-lactam mono- or combination therapy in hospitalized patients with community-acquired pneumonia.

OBJECTIVE: In this observational study, we compared the outcomes of moxifloxacin monotherapy as compared to ß-lactam monotherapy as well as ß-lactam combination therapy in patients with community-acquired pneumonia (CAP). METHODS: Patients recruited within the German Competence Network for CAP (CAPNETZ) were evaluated for treatment regimen. Primary outcome variables were six months overall mortality, pneumonia-related mortality according to clinical judgment and treatment failures (necessity for treatment change and death). RESULTS: Overall, 4091 patients (mean age 64.4±17.8 (range 18-101) years, 2433 male (59.5%)) were included. 2068 patients received moxifloxacin (n=365) or ß-lactam monotherapy (n=1703). 330 patients died within six months. After controlling for confounders in multivariate analysis, moxifloxacin monotherapy had higher survival as compared to ß-lactam monotherapy (hazard ratio for moxifloxacin 0.57, 95% CI 0.35-0.92). Multivariate analysis including interaction terms showed that the protective effect of moxifloxacin was not present for CRB-65 class 0 but increased with higher CRB-65 scores (HR 0.69, 95% CI 0.50-0.96). Regarding pneumonia-related death, moxifloxacin monotherapy was also protective in multivariate analysis (HR 0.36, 95% CI 0.13-0.99). Moxifloxacin was also significantly associated with less treatment failures (p<0.001). In addition, it was not inferior to combination ß-lactam treatment (p=0.062). CONCLUSIONS: In CRB-65 class 0 moxifloxacin was equivalent to ß-lactams. Our observations are in support of a use of moxifloxacin monotherapy in hospitalized patients with moderate CAP (CRB-65 classes 1 and 2).

Hospital-acquired pneumonia in ICU patients.

BACKGROUND: This prospective study aimed at assessing the effect of initial antibiotic therapy on the mortality of patients with hospital-acquired pneumonia (HAP) by analyzing bacterial pathogens and their resistance to antimicrobial agents. METHODS: Included were patients hospitalized in the Department of Anesthesiology and Intensive Care Medicine, Faculty of Medicine and Dentistry, Palacký University Olomouc and University Hospital Olomouc in 2009 who developed HAP. Bacterial pathogens and their resistance to antibiotics were identified using standard microbiological methods. The patient's mortality with respect to their initial antibiotic therapy was statistically analyzed. RESULTS: The group comprised 51 patients with HAP. Early-onset HAP was identified in 7 (14%) patients and late-onset HAP in 44 (86%) patients. The most frequent bacterial pathogens were strains of Klebsiella pneumoniae, Pseudomonas aeruginosa, Burkholderia cepacia complex and Escherichia coli, together accounting for 72%. Eighteen patients died directly due to HAP, an overall mortality rate of 35%. If initial therapy effective against the bacterial pathogen was selected, 21 patients survived and 9 died. If the bacterial pathogens were resistant to the selected initial antibiotic therapy, 9 patients died and 12 survived. CONCLUSIONS: The mortality rates were 30% and 43% for adequate and inadequate antibiotic therapy, respectively. Given the small group of patients, the difference has low statistical significance. However, it does document the clinical impact of bacterial resistance on the survival or death of patients with HAP.

Efficacy of monotherapy and combined antibiotic therapy for carbapenem-resistant Acinetobacter baumannii pneumonia in an immunosuppressed mouse model.

Acinetobacter baumannii is an important cause of nosocomial infection with increasing carbapenem resistance. The aim of this study was to compare the efficacy of colistin+rifampicin and imipenem+rifampicin combinations with that of several other antibiotic regimens against carbapenem-resistant A. baumannii pneumonia using an immunosuppressed mouse model. Three different A. baumannii strains with diverse resistance mechanisms (OXA-51-, IMP-1- and VIM-2-type beta-lactamases) were used. Among the monotherapy regimens, only rifampicin significantly reduced the bacterial load in lungs 24 h after infection with the OXA-51-producing strain. Addition of rifampicin to either imipenem or colistin yielded synergistic results after 48 h. Rifampicin was bactericidal against the IMP-1-producing strain, and only the imipenem+rifampicin combination yielded synergistic effects. In contrast, rifampicin alone was not effective against the VIM-2-producing strain, but the imipenem+rifampicin combination was bacteriostatic even at 24 h post-infection. Tigecycline and amikacin were not effective against any of the three strains. Rifampicin-based combinations were effective against A. baumannii bacteraemia and improved survival regardless of the strain type. Contrary to the similar minimum inhibitory concentration results, the antibacterial effects of rifampicin were quite different according to the strains; a tailored antibiotic strategy must be considered in treatment. Addition of rifampicin to either imipenem or colistin would be effective.