New antimicrobial approaches to gram positive respiratory infections

Nowadays, we face growing resistance among gram-positive and gram-negative pathogens that cause respiratory infection in the hospital and in the community. The spread of penicillin- and macrolide-resistant pneumococci, Community-acquired methicillin-resistant staphylococcus aureus (Ca-MRSA), the emergence of glycopeptide-resistant staphylococci underline the need for underline the need for therapeutic alternatives. A number of new therapeutic agents, with activity against the above Gram (+) respiratory pathogens, as ceftaroline, ceftopibrole, telavancin, tedizolid have become available, either in clinical trials or have been approved for clinical use. Especially, the development of new oral antibiotics, as nemonaxacin, omadacyclin, cethromycin and solithromycin will give a solution to the lack of oral drugs for outpatient treatment. In the future the clinician needs to optimize the use of old and new antibiotics to treat gram (+) respiratory serious infections

Microbial aetiology of community-acquired pneumonia and its relation to severity

Background: The distribution of the microbial aetiology and mortality of community-acquired pneumonia (CAP) was investigated in relation to the clinical setting and severity scores (pneumonia severity index (PSI) and confusion, blood urea nitrogen, respiratory rate, blood pressure, age (CURB-65)). Methods: 3523 patients with CAP were included (15% outpatients, 85% inpatients). The distribution of the microbial aetiology in relation to the clinical setting and severity scores (PSI, CURB-65) and the relative mortality of different aetiologies across the severity scores were analysed. Results: The aetiology was established in 1463 patients (42%), of whom 257 died (7%). The ranking of aetiologies varied according to site of care, with increasing frequency of Streptococcus pneumoniae and mixed aetiologies and decreasing frequency of atypical pathogens in hospitalised patients and those in ICUs. The distribution of aetiologies according to severity scores showed corresponding patterns; however, the severity scores were more sensitive to Gram-negative enteric bacilli (GNEB) and Pseudomonas aeruginosa and less sensitive in identifying mixed aetiologies as moderate- and high-risk conditions. Mortality rates according to aetiology and severity scoring showed increasing mortality rates for all pathogens except atypical pathogens. S pneumoniae had the highest number of deaths while GNEB, P aeruginosa, Staphylococcus aureus and mixed aetiologies had the highest mortality rates. Legionella pneumophila was similarly distributed according to site of care and prognostic scores. Conclusions: CAP due to atypical bacterial pathogens is recognised both clinically and by severity scoring as a low-risk condition. Severity scores are more sensitive in identifying patients with GNEB and P aeruginosa as moderate- and high-risk aetiologies whereas mixed aetiologies may be underestimated

Nursing Home-Acquired Pneumonia: a 10 year single-centre experience

Background: Pneumonia among nursing home (NH) residents has increased considerably in recent years, but it remains unclear whether it should be considered as community-acquired pneumonia (CAP) or a new category of infection. Methods 150 consecutive cases of NH-acquired pneumonia (NHAP) (from 1 February 1997 to 1 July 2007) were analysed. Results: Patients (median age, 82 years; range, 77-87 years) showed numerous co-morbidities, (neurological, 55%; pulmonary, 38%; cardiac, 35%) and severe disability for daily activities (partial, 32%; total, 31%). Cases of NHAP were mainly classified as mild to moderate according to the CRB-65 score (CRB-65 classes 0-1 and 2, 41% each). In-hospital and 30-day mortality were 8.7% and 20%, respectively. Aetiology was defined in 57 cases (38%). The most common isolates were Streptococcus pneumoniae (58%), Enterobacteriaceae (Gram-negative bacteria (GNB)) (9%), atypical bacteria (7%), respiratory viruses (5%), methicillin-resistant Staphylococcus aureus (MRSA) (5%) and Legionella pneumophila (5%). The most frequent causes of treatment inadequacy were use of β-lactams alone (25%) and lack of aspiration assessment (15%). Prognostic factors of 1-month mortality were neurological comorbidities (OR 4.5; 95% CI 1.3 to 15.7; p=0.020), septic shock (OR 6.6; 95% CI 1.3 to 34.0; p=0.025), pleural effusion (OR 3.6; 95% CI 1.1 to 11.7; p=0.036) and isolation of GNB or MRSA (OR 16.4; 95% CI 2.1 to 128.9; p=0.008). Conclusions: The patients show clinical characteristics (eg, age and co-morbidities) comparable with those with hospital-acquired pneumonia. However, microbiological and mortality data of patients with NHAP are more similar to the data of those with CAP. Isolation of GNB or MRSA was associated with increased mortality risk. CAP empirical antibiotic coverage is still indicated in NHAP, although specific risk factors for multidrug-resistant infections should be assessed on an individual basis

Community-Acquired Pneumonia Due to Multidrug- and Non–Multidrug-Resistant Pseudomonas aeruginosa

Background: Pseudomonas aeruginosa is not a frequent pathogen in community-acquired pneumonia (CAP). However, in patients with severe CAP, P aeruginosa can be the etiology in 1.8% to 8.3% of patients, with a case-fatality rate of 50% to 100%. We describe the prevalence, clinical characteristics, outcomes, and risk factors associated with CAP resulting from multidrug-resistant (MDR) and non-MDR P aeruginosa. Methods: Prospective observational study of 2,023 consecutive adult patients with CAP with definitive etiology. Results: P aeruginosa was found in 77 (4%) of the 2,023 cases with microbial etiology. In 22 (32%) of the 68 cases of P aeruginosa with antibiogram data, the isolates were MDR. Inappropriate therapy was present in 49 (64%) cases of P aeruginosa CAP, including 17/22 (77%) cases of MDR P aeruginosa CAP. Male sex, chronic respiratory disease, C-reactive protein <12.35 mg/dL, and pneumonia severity index risk class IV to V were independently associated with P aeruginosa CAP. Prior antibiotic treatment was more frequent in MDR P aeruginosa CAP compared with non-MDR P aeruginosa (58% vs 29%, P = .029), and was the only risk factor associated with CAP resulting from MDR P aeruginosa. In the multivariate analysis, age ≥65 years, CAP resulting from P aeruginosa, chronic liver disease, neurologic disease, nursing home, criteria of ARDS, acute renal failure, ICU admission, and inappropriate empiric treatment were the factors associated with 30-day mortality. Conclusions: P aeruginosa is an individual risk factor associated with mortality in CAP. The risk factors described can help clinicians to suspect P aeruginosa and MDR P aeruginosa

Twenty-year trend in mortality among hospitalized patients with pneumococcal community-acquired pneumonia

Background There is only limited information on mortality over extended periods in hospitalized patients with pneumococcal community-acquired pneumonia (CAP). We aimed to evaluate the 30-day mortality and whether is changed over a 20-year period among immunocompetent adults hospitalized with pneumococcal CAP. Methods We conducted a retrospective observational study of data that were prospectively collected at the Hospital Clinic of Barcelona of all adult patients hospitalized with diagnosis of pneumococcal CAP over a 20-year period. To aid analysis, results were divided into four periods of 5 years each (1997-2001, 2002-2006, 2007-2011, 2012-2016). The primary outcome was 30-day mortality, but secondary outcomes included intensive care unit (ICU) admission, lengths of hospital and ICU-stays, ICU-mortality, and need of mechanical ventilation. Results From a cohort of 6,403 patients with CAP, we analyzed the data for 1,120 (17%) adults with a diagnosis of pneumococcal CAP. Over time, we observed decreases in the rates of alcohol consumption, smoking, influenza vaccination, and older patients (age ≥65 years), but increases in admissions to ICU and the need for non-invasive mechanical ventilation. The overall 30-day mortality rate was 8% (95% confidence interval, 6%-9%; 84 of 1,120 patients) and did not change significantly between periods (p = 0.33). Although, we observed a decrease in ICU-mortality comparing the first period (26%) to the second one (10%), statistical differences disappeared with adjustment (p0.38). Conclusion Over time, 30-day mortality of hospitalized pneumococcal CAP did not change significantly. Nor did it change in the propensity-adjusted multivariable analysis. Since mortality in pneumococcal pneumonia has remained unaltered for many years despite the availability of antimicrobial agents with proven in vitro activity, other non-antibiotic strategies should be investigated

Microbiology and outcomes of community acquired pneumonia in non cystic-fibrosis bronchiectasis patients

Background: It is general belief that Non-cystic fibrosis bronchiectasis (NCFB) is characterized by frequent community-acquired pneumonia. Nonetheless, the knowledge on clinical characteristics of CAP in NCFBE is poor and no specific recommendations are available. We aim to investigate clinical and microbiological characteristics of NCFBE patients with CAP. Methods: Prospective observational study of 3495 CAP patients (2000-2011). Results: We found 90 (2.0%) NCFBE-CAP that in comparison with non-bronchiectatic CAP (n, 3405) showed older age (mean ± [SD], NCFBE-CAP 73 ± 14 vs. CAP 65 ± 19yrs), more vaccinations (pneumococcal: 35% vs. 14%; influenza: 60% vs. 42%), comorbidities (n ≥ 2: 43% vs. 25%), previous antibiotics (38% vs. 22%), and inhaled steroids (53% vs. 16%) (p < 0.05 each). Streptococcus pneumoniae was the most frequent isolate in both groups (NCFBE-CAP 44.4% vs. CAP 42.7%; p = 0.821) followed by respiratory virus, mixed infections and atypical bacteria. Considering overall frequencies of the main pathogens (including monomicrobial and mixed infections) Pseudomonas aeruginosa (15.5% vs. 2.9%; p < 0.001) and Enterobacteriaceae (8.8% vs. 2.4%; p = 0.025) were more prevalent in NCFBE-CAP patients than in CAP. Despite these clinical and microbiological differences, NCFBE-CAP showed similar outcomes to CAP patients (mortality, length of hospital stay, etc.). Conclusions: NCFBE-CAP patients are usually older and have more comorbidities but similar outcomes than general CAP population. Usual CAP pathogens, such as S. pneumoniae, are also involved in NCFBE-CAP but P. aeruginosa and other Enterobacteriaceae were globally more frequent than in CAP. Therefore, a wide microbiological investigation should be recommended in all NCFBE-CAP cases as well as routine pneumococcal vaccination for prevention of pneumonia

Evaluation of the MagicplexTM sepsis real-time test for the rapid diagnosis of bloodstream infections in adults

Sepsis is a serious health condition worldwide, affecting more than 30 million people globally each year. Blood culture (BC) is generally used to diagnose sepsis because of the low quantity of microbes occurring in the blood during such infections. However, ~50% of bloodstream infections (BSI) give negative BC, this figure being higher for sepsis, which delays the start of appropriate antimicrobial therapy. This prospective study evaluated a multiplex real-time polymerase chain reaction, the MagicplexTM Sepsis test (MP), for the detection of pathogens from whole blood, comparing it to routine BC. We analyzed 809 blood samples from 636 adult patients, with 132/809 (16.3%) of the samples positive for one or more relevant microorganism according to BC and/or MP. The sensitivity and specificity of MP were 29 and 95%, respectively, while the level of agreement between BC and MP was 87%. The rate of contaminated samples was higher for BC (10%) than MP (4.8%) (P < 0.001). Patients with only MP-positive samples were more likely to be on antimicrobial treatment (47%) than those with only BC-positive samples (18%) (P = 0.002). In summary, the MP test could be useful in some clinical setting, such as among patients on antibiotic therapy. Nevertheless, a low sensitivity demonstrated impairs its use as a part of a routine diagnostic algorithm

Community-Acquired Pneumococcal Pneumonia in Virologically Suppressed HIV-Infected Adult Patients: A Matched Case-Control Study

Background: The study aimed to investigate whether the clinical presentations and outcomes (length of stay, ICU admission, and 30-day mortality) of pneumococcal pneumonia in virologically suppressed patients who were HIV-infected on ART with a CD4+ T-cell count > 350 cells/mm3 are comparable to those seen in patients with HIV, using a case-control design. Methods: A case-control study was carried out in Hospital Clinic, Barcelona, Spain (2001-2016). Control patients were matched by age (±10 years), sex, comorbidities, and pneumonia diagnosis in the same calendar period. Clinical presentation and outcomes of pneumococcal pneumonia in patients who were and were not infected with HIV were compared. Results: Pneumococcal pneumonia was studied in 50 cases (HIV infection) and 100 control patients (non-HIV infection). Compared with the control patients, case patients had higher rates of influenza (14% vs 2%, P = .007) and pneumococcal vaccination (10% vs 1%, P = .016). The group of cases also presented a higher rate of coinfection with hepatitis B virus (6% vs 0%, P = .036). Both groups presented similar ICU admission (18% vs 27%, P = .22), need for mechanical ventilation (12% vs 8%; P = .43), length of stay (7 days vs 7 days, P = .76), and 0% of 30-day mortality. No evidence was found of a more severe presentation or a worse clinical outcome in cases than in control patients. Conclusions: Pneumococcal pneumonia episodes requiring hospitalization in virologically suppressed patients with HIV with > 350 CD4+ T-cell count/mm3 were neither more severe nor had worse prognosis compared with uninfected patients. These results support the fact that such patients do not need treatment, admission, or care sites different to the general population

Evaluation of a Mixing versus a Cycling Strategy of Antibiotic Use in Critically-Ill Medical Patients: Impact on Acquisition of Resistant Microorganisms and Clinical Outcomes

OBJECTIVE: To compare the effect of two strategies of antibiotic use (mixing vs. cycling) on the acquisition of resistant microorganisms, infections and other clinical outcomes. METHODS: Prospective cohort study in an 8-bed intensive care unit during 35- months in which a mixing-cycling policy of antipseudomonal beta-lactams (meropenem, ceftazidime/piperacillin-tazobactam) and fluoroquinolones was operative. Nasopharyngeal and rectal swabs and respiratory secretions were obtained within 48h of admission and thrice weekly thereafter. Target microorganisms included methicillin-resistant S. aureus, vancomycin-resistant enterococci, third-generation cephalosporin-resistant Enterobacteriaceae and non-fermenters. RESULTS: A total of 409 (42%) patients were included in mixing and 560 (58%) in cycling. Exposure to ceftazidime/piperacillin-tazobactam and fluoroquinolones was significantly higher in mixing while exposure to meropenem was higher in cycling, although overall use of antipseudomonals was not significantly different (37.5/100 patient-days vs. 38.1/100 patient-days). There was a barely higher acquisition rate of microorganisms during mixing, but this difference lost its significance when the cases due to an exogenous Burkholderia cepacia outbreak were excluded (19.3% vs. 15.4%, OR 0.8, CI 0.5-1.1). Acquisition of Pseudomonas aeruginosa resistant to the intervention antibiotics or with multiple-drug resistance was similar. There were no significant differences between mixing and cycling in the proportion of patients acquiring any infection (16.6% vs. 14.5%, OR 0.9, CI 0.6-1.2), any infection due to target microorganisms (5.9% vs. 5.2%, OR 0.9, CI 0.5-1.5), length of stay (median 5 d for both groups) or mortality (13.9 vs. 14.3%, OR 1.03, CI 0.7-1.3). CONCLUSIONS: A cycling strategy of antibiotic use with a 6-week cycle duration is similar to mixing in terms of acquisition of resistant microorganisms, infections, length of stay and mortality

Time-to-positivity, type of culture media and oxidase test performed on positive blood culture vials to predict Pseudomonas aeruginosa in patients with Gram-negative bacilli bacteraemia

OBJECTIVE: The aim of this study was to determine the usefulness of oxidase test and time-to-positivity (TTP) in aerobic and anaerobic blood culture vials to detect the presence of Pseudomonas aeruginosa in patients with Gram-negative bacilli (GNB) bacteraemia. METHODS: TTP was recorded for each aerobic and anaerobic blood culture vial of monomicrobial bacteraemia due to GNB. Oxidase test was performed in a pellet of the centrifuged content of the positive blood culture. An algorithm was developed in order to perform the oxidase test efficiently taking into account TTP and type of vial. RESULTS: A total of 341 episodes of GNB bacteraemia were analysed. Sensitivity, specificity, positive predictive value and negative predictive value of the oxidase test performed on positive vials with GNB to predict P. aeruginosa were 95%, 99%, 91%, and 99%, respectively. When growth was first or exclusively detected in anaerobic vials, P. aeruginosa was never identified hence the performance of the oxidase test could be avoided. When growth was only or first detected in aerobic vials, a TTP≥8h predicted P. aeruginosa in 37% or cases (63 of 169), therefore oxidase test is highly recommended. CONCLUSIONS: Oxidase test performed onto positive blood culture vials previously selected by TTP and type of vials is an easy and inexpensive way to predict P. aeruginosa. In most cases, this can lead to optimization of treatment in less than 24 hours