Treatable traits and challenges in the clinical management of non-tuberculous mycobacteria lung disease in people with cystic fibrosis.

INTRODUCTION: Over the last ten years an increasing prevalence and incidence of non-tuberculous mycobacteria (NTM) has been reported among patients with cystic fibrosis (CF) Viviani (J Cyst Fibros, 15(5):619-623, 2016). NTM pulmonary disease has been associated with negative clinical outcomes and often requires pharmacological treatment. Although specific guidelines help clinicians in the process of diagnosis and clinical management, the focus on the multidimensional assessment of concomitant problems is still scarce. MAIN BODY: This review aims to identify the treatable traits of NTM pulmonary disease in people with CF and discuss the importance of a multidisciplinary approach in order to detect and manage all the clinical and behavioral aspects of the disease. The multidisciplinary complexity of NTM pulmonary disease in CF requires careful management of respiratory and extra-respiratory, including control of comorbidities, drug interactions and behavioral factors as adherence to therapies. CONCLUSIONS: The treatable trait strategy can help to optimize clinical management through systematic assessment of all the aspects of the disease, providing a holistic treatment for such a multi-systemic and complex condition.

Household Costs Associated with Hospitalization of Children with Severe Pneumonia in Quito, Ecuador.

Pneumonia remains a leading cause of morbidity and mortality in young children. The total cost of pneumonia-related hospitalization, including household-level cost, is poorly understood. To better understand this burden in an urban setting in South America, we incorporated a cost study into a trial assessing zinc supplements in treatment of severe pneumonia among children aged 2-59 months at a public hospital in Quito, Ecuador, which provides such treatment at no charge. Data were collected from children's caregivers at hospitalization and discharge on out-of-pocket payments for medical and nonmedical items, and on employment and lost work time. Analyses encompassed three categories: direct medical costs, direct nonmedical costs, and indirect costs, which covered foregone wages (from caregivers' self-reported lost earnings) and opportunity cost of caregivers' lost time (based on the unskilled labor wage in Ecuador). Caregivers of 153 children completed all questionnaires. Overall, 57% of children were aged less than 12 months, and 46% were female. Just over 50% of mothers and fathers had completed middle school. Most reported direct costs, which averaged $33. Most also reported indirect costs, the mean of which was $74. Fifty-seven reported lost earnings (mean = $79); 29 reported lost time (estimated mean cost = $37). Stratified analyses revealed similar costs for children < 12 months and ≥ 12 months, with variations for specific items. Costs for hospital-based treatment of severe pneumonia in young children represent a major burden for households in low- to middle-income settings, even when such treatment is intended to be provided at no cost.

Hafnia alvei pneumonia: a rare cause of infection in the multimorbid or immunocompromised.

Hafnia alvei is a rare, poorly understood commensal bacterium which has, on occasion, been shown to infect humans. We present two cases. The first patient presented with a 1-week history of dyspnoea, pleurisy and a productive cough, and the second with a prodrome of fatigue and night sweats. The former had a history of severe chronic obstructive pulmonary disease and the latter had a history of Crohn's disease. Both patients had underlying comorbidities and immunosuppression, but differed in presentation, radiological findings and recovery. This case series aims to remind readers of the broad differential of pathogens that can lead to disease in the immunocompromised and that one should not dismiss atypical cultured bacteria as commensal too hastily.

How should we treat acinetobacter pneumonia?

PURPOSE OF REVIEW: To describe recent data about Acinetobacter baumannii pneumonia epidemiology and the therapeutic options including adjunctive nebulized therapy. RECENT FINDINGS: A. baumannii is a major cause of nosocomial pneumonia in certain geographic areas affecting mainly debilitated patients, with prolonged hospitalization and broad-spectrum antimicrobials. Inappropriate empirical treatment has clearly been associated with increased mortality in A. baumannii pneumonia. Carbapenems may not be considered the treatment of choice in areas with high rates of carbapenem-resistant A. baumannii. Nowadays, polymyxins are the antimicrobials with the greatest level of in-vitro activity. Colistin is the antimicrobial most widely used although polymyxin B is associated with less renal toxicity. It is clear that lung concentrations of polymyxins are suboptimal in a substantial proportion of patients. This issue has justified the use of combination therapy or adjunctive nebulized antibiotics. Current evidence does not allow us to recommend combination therapy for A. baumannii pneumonia. Regarding nebulized antibiotics, it seems reasonable to use in patients who are nonresponsive to systemic antibiotics or A. baumannii isolates with colistin minimum inhibitory concentrations close to the susceptibility breakpoints. Cefiderocol, a novel cephalosporin active against A. baumannii, may represent an attractive therapeutic option if ongoing clinical trials confirm preliminary results. SUMMARY: The optimal treatment for multidrug-resistant A. baumannii pneumonia has not been established. New therapeutic options are urgently needed. Well designed, randomized controlled trials must been conducted to comprehensively evaluate the effectiveness and safety of nebulized antibiotics for the treatment of A. baumannii pneumonia.

Activity of Ceftolozane-Tazobactam against Pseudomonas aeruginosa and Enterobacteriaceae Isolates Collected from Respiratory Tract Specimens of Hospitalized Patients in the United States during 2013 to 2015.

The activities of ceftolozane-tazobactam and comparator agents against organisms deemed to be the cause of pneumonia among patients hospitalized in the United States during 2013 to 2015 were evaluated. Organisms included 1,576 Pseudomonas aeruginosa and 2,362 Enterobacteriaceae isolates susceptibility tested using reference broth microdilution methods. Ceftolozane-tazobactam, cefepime, ceftazidime, meropenem, and piperacillin-tazobactam inhibited 96.3%, 84.8%, 83.5%, 80.0%, and 78.6%, respectively, of the P. aeruginosa isolates. Ceftolozane-tazobactam inhibited 77.5 to 85.1% of isolates nonsusceptible to antipseudomonal ß-lactams and 86.6% and 71.0% of the 372 (23.6% overall) multidrug- and 155 (9.8%) extensively drug-resistant isolates tested. The activity of this combination was greater than those of other ß-lactams evaluated against P. aeruginosa groups across all U.S. census divisions. Ceftolozane-tazobactam was active against 90.6% of the Enterobacteriaceae, being less active than only meropenem (95.6% susceptible) among the ß-lactams evaluated. Against 145 Escherichia coli and Klebsiella pneumoniae isolates carrying extended-spectrum-ß-lactamase (ESBL)-encoding genes without carbapenemases, ceftolozane-tazobactam inhibited 82.8% of these isolates and was more active than cefepime and piperacillin-tazobactam (15.2% and 74.3% susceptible, respectively). ESBL genes included in this analysis were mainly blaCTX-M-15-like (89 isolates) and blaCTX-M-14-like (22) genes but also blaSHV (31) and blaTEM (3). Ceftolozane-tazobactam also displayed activity (84.6% susceptible) against 13 isolates harboring acquired AmpC genes. All ß-lactams displayed limited activity against blaKPC-carrying isolates. Ceftolozane-tazobactam was the most active ß-lactam tested against P. aeruginosa isolates from isolates that were the probable cause of pneumonia and displayed in vitro activity against Enterobacteriaceae, including isolates resistant to cephalosporins and carrying ESBL genes.

Solithromycin: A novel ketolide antibiotic.

PURPOSE: The pharmacology, pharmacokinetics, pharmacodynamics, antimicrobial activity, clinical safety, and current regulatory status of solithromycin are reviewed. SUMMARY: Solithromycin is a novel ketolide antibiotic developed for the treatment of community-acquired bacterial pneumonia (CABP). Its pharmacologic, pharmacokinetic, and pharmacodynamic properties provide activity against a broad range of intracellular organisms, including retained activity against pathogens displaying various mechanisms of macrolide resistance. Phase III clinical trials of solithromycin demonstrated noninferiority of both oral and i.v.-to-oral regimens of 5-7 days' duration compared with moxifloxacin for patients with moderately severe CABP. Nearly one third of patients receiving i.v. solithromycin experienced infusion-site reactions. Although no liver-related adverse events were reported in patients receiving oral solithromycin, more patients receiving i.v.-to-oral solithromycin experienced asymptomatic, transient transaminitis, with alanine transaminase levels of >3 to >5 times the upper limit, compared with those treated with moxifloxacin. These results led the Food and Drug Administration to conclude that the solithromycin new drug application was not approvable as filed, adding that the risk of hepatotoxicity had not yet been adequately characterized. The agency further recommended a comparative study of patients with CABP to include approximately 9,000 patients exposed to solithromycin in order to exclude drug-induced liver injury events occurring at a rate of 1 in 3,000 with 95% probability. CONCLUSION: Solithromycin is a novel ketolide antibiotic with activity against a broad spectrum of intracellular organisms, including those displaying macrolide resistance. While demonstrating noninferiority to a current first-line agent in the treatment of CABP, concerns for drug-induced liver injury and infusion-site reactions have placed its regulatory future in doubt.

Effect of quality of colostrum on health, growth and immunoglobulin G concentration in Holstein calves in a hot environment.

The aim of this study was to determine the effect of ingestion of pasteurized and subsequently frozen-thawed pooled colostrum (≥50 mg Ig/mL) with different bacterial counts and immunoglobulin concentration (IgC) on the occurrence of diarrhea and pneumonia in 306 neonatal Holstein calves in a hot environment. Calves were assigned to be fed colostrum with total bacterial counts (TBC) lower or greater than 100 000 colony-forming units (cfu)/mL, total coliform counts (TCC) greater or lower than 10 000 cfu/mL, and IgC lower or higher than 85 mg Ig/mL. Calves fed colostrum with TBC ≥100 000 cfu/mL were more likely (risk ratio 1.34, confidence interval 1.05-1.71; P < 0.05) to present pneumonia than calves receiving colostrum with lower TBC (incidence 53.2 vs. 39.8%). Calves fed colostrum with high TCC had increased chances of suffering pneumonia (51.4 vs. 42.1%; P < 0.05) than calves fed colostrum with lower TCC. Calves fed colostrum with ≥85 mg Ig/mL tended to present higher daily weight gain (505 ± 113 vs. 484 ± 126 g; P = 0.09). TBC and TCC in colostrum did not influence the incidence rate of diarrhea. It was concluded that under the conditions of the present study, heavy contamination of on-farm pasteurized frozen-thawed colostrum is seemingly unavoidable and this contamination poses a threat for pneumonia, but not for diarrhea.

Antimicrobial Activity of Ceftazidime-Avibactam against Gram-Negative Bacteria Isolated from Patients Hospitalized with Pneumonia in U.S. Medical Centers, 2011 to 2015.

Bacterial isolates were collected from patients hospitalized with pneumonia (PHP), including ventilator-associated pneumonia (VAP), from 76 U.S. medical centers in 2011 to 2015. The Gram-negative organisms (n = 11,185, including 1,097 from VAP) were tested for susceptibility to ceftazidime-avibactam and comparators by the broth microdilution method. ß-Lactamase-encoding genes were screened using a microarray-based assay on selected isolates. Pseudomonas aeruginosa and Klebsiella spp. were the most common Gram-negative bacteria isolated from PHP and VAP. Ceftazidime-avibactam was very active against P. aeruginosa (n = 3,402; MIC50/MIC90, 2 and 4 µg/ml; 96.6% susceptible), including isolates nonsusceptible to meropenem (86.3% susceptible to ceftazidime-avibactam), piperacillin-tazobactam (85.6% susceptible), or ceftazidime (80.6% susceptible). Ceftazidime-avibactam was also highly active against Enterobacteriaceae (MIC50/MIC90, 0.12 and 0.5 µg/ml; 99.9% susceptible), including carbapenem-resistant Enterobacteriaceae (CRE) (n = 189; MIC50/MIC90, 0.5 and 2 µg/ml; 98.0% susceptible) and multidrug-resistant (MDR) (n = 674; MIC50/MIC90, 0.25 and 1 µg/ml; 98.8% susceptible) and extensively drug-resistant (XDR) (n = 156; MIC50/MIC90, 0.5 and 2 µg/ml; 98.1% susceptible) Enterobacteriaceae isolates, as well as Klebsiella species isolates showing an extended-spectrum ß-lactamase (ESBL) screening-positive phenotype (n = 433; MIC50/MIC90, 0.25 and 1 µg/ml; 99.5% susceptible). Among Enterobacter spp. (24.8% ceftazidime nonsusceptible), 99.8% of the isolates, including 99.4% of ceftazidime-nonsusceptible isolates, were susceptible to ceftazidime-avibactam. The most common ß-lactamases detected among Klebsiella pneumoniae and E. coli isolates were K. pneumoniae carbapenemase (KPC)-like and CTX-M-15, respectively. Only 8 of 6,209 Enterobacteriaceae isolates (0.1%) were ceftazidime-avibactam nonsusceptible, three NDM-1-producing strains with ceftazidime-avibactam MIC values of >32 µg/ml and five isolates with ceftazidime-avibactam MIC values of 16 µg/ml and negative results for all ß-lactamases tested. Susceptibility rates among isolates from VAP were generally similar or slightly higher than those from all PHP.

Characterization of Mycobacterium Abscessus Subtypes in Shanghai of China: Drug Sensitivity and Bacterial Epidemicity as well as Clinical Manifestations.

The aim of the study was to investigate the epidemic characteristics of Mycobacterium abscessus in Shanghai.Fifty-five strains from 55 M. abscessus pulmonary disease patients were isolated. Drug sensitivity was measured by a broth microdilution method. Subtypes of M. abscessus were identified by DNA sequencing. Multilocus sequence typing (MLST), mining spanning tree (MST), and pulsed-field gel electrophoresis (PFGE) were used to analyze sequence types (ST) and clonal complexes (CC). Clinical manifestations were assessed by CT imaging.We identified 42 A isolates, 11 M, and 2 B-subtypes. A and M were highly sensitive to tigecycline and amikacin (97.6-100%). The A-type easily developed drug resistance against clarithromycin. Both types were highly resistance to sulfonamides, moxifloxacin, doxycycline, imipenem, and tobramycin. MLST analysis identified 41 STs including 32 new STs. The MST algorithm distributed 55 isolates into 12 separate CC. The PFGE analysis exhibited 53 distinct restriction patterns and the M-type was closely clustered according to their ST and CC numbers. CT imaging showed that tree-in-bud and patch shadow were commonly observed in M-type, whereas pulmonary cavities were often found in A-type infection patients (P < 0.001).ST1 in A and ST23 in M-type were the main epidemic strains in Shanghai. The M-type appeared to be prone to epidemic nosocomial transmission.

Implementation of Computerized Physician Order Entry Is Associated With Increased Thrombolytic Administration for Emergency Department Patients With Acute Ischemic Stroke.

STUDY OBJECTIVE: Electronic health record systems with computerized physician order entry and condition-specific order sets are intended to standardize patient management and minimize errors of omission. However, the effect of these systems on disease-specific process measures and patient outcomes is not well established. We seek to evaluate the effect of computerized physician order entry electronic health record implementation on process measures and short-term health outcomes for patients hospitalized with acute ischemic stroke. METHODS: We conducted a quasi-experimental cohort study of patients hospitalized for acute ischemic stroke with concurrent controls that took advantage of the staggered implementation of a comprehensive computerized physician order entry electronic health record across 16 medical centers within an integrated health care delivery system from 2007 to 2012. The study population included all patients admitted to the hospital from the emergency department (ED) for acute ischemic stroke, with an initial neuroimaging study within 2.5 hours of ED arrival. We evaluated the association between the availability of a computerized physician order entry electronic health record and the rates of ED intravenous tissue plasminogen activator administration, hospital-acquired pneumonia, and inhospital and 90-day mortality, using doubly robust estimation models to adjust for demographics, comorbidities, secular trends, and concurrent primary stroke center certification status at each center. RESULTS: Of 10,081 eligible patients, 6,686 (66.3%) were treated in centers after the computerized physician order entry electronic health record had been implemented. Computerized physician order entry was associated with significantly higher rates of intravenous tissue plasminogen activator administration (rate difference 3.4%; 95% confidence interval 0.8% to 6.0%) but not with significant rate differences in pneumonia or mortality. CONCLUSION: For patients hospitalized for acute ischemic stroke, computerized physician order entry use was associated with increased use of intravenous tissue plasminogen activator.

Angiotensin-converting enzyme inhibitors and bacterial pneumonia in patients with Parkinson disease.

BACKGROUND: To evaluate the association of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers with pneumonia development in patients with Parkinson's disease (PD). METHODS: The study cohort consisted of patients aged 50 years or older who were initially diagnosed with PD and had hypertension. We assessed the patients' exposure statuses and accumulated doses of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers. We then evaluated the risk of pneumonia development in the patients who were exposed to these drugs and those who were not. RESULTS: We examined 2,310 patients. During the observation period, 608 patients developed pneumonia. Angiotensin-converting enzyme inhibitors were associated with a lower risk of pneumonia. This association was dose-dependent. CONCLUSION: Angiotensin-converting enzyme inhibitor use was associated with a dose-dependent reduction in the risk of pneumonia in patients with PD and hypertension.

Etiologies of illness among patients meeting integrated management of adolescent and adult illness district clinician manual criteria for severe infections in northern Tanzania: implications for empiric antimicrobial therapy.

We describe the laboratory-confirmed etiologies of illness among participants in a hospital-based febrile illness cohort study in northern Tanzania who retrospectively met Integrated Management of Adolescent and Adult Illness District Clinician Manual (IMAI) criteria for septic shock, severe respiratory distress without shock, and severe pneumonia, and compare these etiologies against commonly used antimicrobials, including IMAI recommendations for emergency antibacterials (ceftriaxone or ampicillin plus gentamicin) and IMAI first-line recommendations for severe pneumonia (ceftriaxone and a macrolide). Among 423 participants hospitalized with febrile illness, there were 25 septic shock, 37 severe respiratory distress without shock, and 109 severe pneumonia cases. Ceftriaxone had the highest potential utility of all antimicrobials assessed, with responsive etiologies in 12 (48%) septic shock, 5 (14%) severe respiratory distress without shock, and 19 (17%) severe pneumonia illnesses. For each syndrome 17-27% of participants had etiologic diagnoses that would be non-responsive to ceftriaxone, but responsive to other available antimicrobial regimens including amphotericin for cryptococcosis and histoplasmosis; anti-tuberculosis therapy for bacteremic disseminated tuberculosis; or tetracycline therapy for rickettsioses and Q fever. We conclude that although empiric ceftriaxone is appropriate in our setting, etiologies not explicitly addressed in IMAI guidance for these syndromes, such as cryptococcosis, histoplasmosis, and tetracycline-responsive bacterial infections, were common.

A cross-sectional study of the clinical characteristics of hospitalized children with community-acquired pneumonia in eight eastern cities in China.

BACKGROUND: Community-acquired pneumonia in children is common in China. To understand current clinical characteristics and practice, we conducted a cross-sectional study to analyze quality of care on childhood pneumonia in eight eastern cities in China. METHODS: Consecutive hospital records between January 1, 2010 and December 31, 2010 were collected from 13 traditional Chinese medicine (TCM) and western medicine (WM) hospitals in February, May, August, and November (25 cases per season, 100 cases over the year), respectively. A predesigned case report form was used to extract data from the hospital medical records. RESULTS: A total of 1298 cases were collected and analyzed. Symptoms and signs upon admission at TCM and WM hospitals were cough (99.3% vs. 98.6%), rales (84.8% vs. 75.0%), phlegm (83.3% vs. 49.1%), and fever (74.9% vs. 84.0%) in frequency. Patients admitted to WM hospitals had symptoms and signs for a longer period prior to admission than patients admitted to TCM hospitals. Testing to identify etiologic agents was performed in 1140 cases (88.4%). Intravenous antibiotics were administered in 99.3% (595/598) of cases in TCM hospitals and in 98.6% (699/700) of cases in WM hospitals. Besides, Chinese herbal extract injection was used more frequently in TCM hospitals (491 cases, 82.1%) than in WM hospitals (212 cases, 30.3%) (p < 0.01). At discharge, 818 cases (63.0%) were clinically cured, with a significant difference between the cure rates in TCM (87.6%) and WM hospitals (42.0%) (OR = 9.8, 95% confidence interval (CI): 7.3 ~ 12.9, p < 0.01). Pathogen and previous medical history were more likely associated with the disappearance of rales (OR = 7.2, 95% CI: 4.8 ~ 10.9). Adverse effects were not reported from the medical records. CONCLUSIONS: Intravenous use of antibiotics is highly prevalent in children with community-acquired pneumonia regardless of aetiology. There was difference between TCM and WM hospitals with regard to symptom profile and the use of antibiotics. Intravenous use of herbal injection was higher in TCM hospitals than in WM hospitals. Most of the cases were diagnosed based on clinical signs and symptoms without sufficient confirmation of aetiology. Audit of current practice is urgently needed to improve care.

Approach to common bacterial infections: community-acquired pneumonia.

Community-acquired pneumonia (CAP) occurs more often in early childhood than at almost any other age. Many microorganisms are associated with pneumonia, but individual pathogens are difficult to identify, which poses problems in antibiotic management. This article reviews the common as well as new, emerging pathogens, as well as the guidelines for management of pediatric CAP. Current guidelines for pediatric CAP continue to recommend the use of high-dose amoxicillin for bacterial CAP and azithromycin for suspected atypical CAP (usually caused by Mycoplasma pneumoniae) in children.

[Bacterial pneumonia in HIV-infected patients (excluding mycobacterial infection)]. / Pneumonies bactériennes chez les personnes infectées par le VIH (hors mycobactéries).

Respiratory infections are the most common complications in HIV patients, regardless of the degree of immunosuppression. Even though antiretroviral therapy has a protective effect on the risk of bacterial pneumonia, this still remains high (including those with CD(4)>500/mm(3)). The most frequently isolated bacteria are Streptococcus pneumoniae and Haemophilus influenzae. The clinical and radiological presentations of lower respiratory tract infections in HIV patients are quite variable. The clinical presentation is more severe and the radiological presentation is more atypical if the immunosuppression is severe. The first-line antibiotic therapy is an injectable third-generation cephalosporin (ceftriaxone or cefotaxime) or co-amoxiclav. Pneumococcal vaccination (as well as influenza vaccine) is recommended. Although rare, Nocardia spp. and Rhodococcus equi seem more common among AIDS patients.

Diagnosis and management of community-acquired pneumonia in adults.

Community-acquired pneumonia is diagnosed by clinical features (e.g., cough, fever, pleuritic chest pain) and by lung imaging, usually an infiltrate seen on chest radiography. Initial evaluation should determine the need for hospitalization versus outpatient management using validated mortality or severity prediction scores. Selected diagnostic laboratory testing, such as sputum and blood cultures, is indicated for inpatients with severe illness but is rarely useful for outpatients. Initial outpatient therapy should include a macrolide or doxycycline. For outpatients with comorbidities or who have used antibiotics within the previous three months, a respiratory fluoroquinolone (levofloxacin, gemifloxacin, or moxifloxacin), or an oral beta-lactam antibiotic plus a macrolide should be used. Inpatients not admitted to an intensive care unit should receive a respiratory fluoroquinolone, or a beta-lactam antibiotic plus a macrolide. Patients with severe community-acquired pneumonia or who are admitted to the intensive care unit should be treated with a beta-lactam antibiotic, plus azithromycin or a respiratory fluoroquinolone. Those with risk factors for Pseudomonas should be treated with a beta-lactam antibiotic (piperacillin/tazobactam, imipenem/cilastatin, meropenem, doripenem, or cefepime), plus an aminoglycoside and azithromycin or an antipseudomonal fluoroquinolone (levofloxacin or ciprofloxacin). Those with risk factors for methicillin-resistant Staphylococcus aureus should be given vancomycin or linezolid. Hospitalized patients may be switched from intravenous to oral antibiotics after they have clinical improvement and are able to tolerate oral medications, typically in the first three days. Adherence to the Infectious Diseases Society of America/American Thoracic Society guidelines for the management of community-acquired pneumonia has been shown to improve patient outcomes. Physicians should promote pneumococcal and influenza vaccination as a means to prevent community-acquired pneumonia and pneumococcal bacteremia.

Fluoroquinolones in the management of community-acquired pneumonia in primary care.

A literature search was conducted to evaluate the pharmacokinetic and pharmacodynamic profile of the respiratory fluoroquinolones (gemifloxacin, levofloxacin and moxifloxacin) and their efficacy and safety in the management of community-acquired pneumonia (CAP). Data show that CAP is a common presentation in primary care practice, and is associated with high rates of morbidity and mortality, particularly in the elderly. Although the causative pathogens differ depending on treatment setting and patient factors, Streptococcus pneumoniae is the primary pathogen in all treatment settings. As a class, the respiratory fluoroquinolones have a very favorable pharmacokinetic and pharmacodynamic profile. Pharmacodynamic criteria suggest that moxifloxacin and gemifloxacin are more potent against S. pneumoniae, which may have the added benefit of reducing resistance selection and enhancing bacterial eradication. The respiratory fluoroquinolones are also generally well tolerated, and are first-line options for outpatient treatment of CAP in patients with comorbidities or previous antibiotic use.

Chemoprophylactic effects of azithromycin against Rhodococcus equi-induced pneumonia among foals at equine breeding farms with endemic infections.

OBJECTIVE: To determine the effect of azithromycin chemoprophylaxis on the cumulative incidence of pneumonia caused by Rhodococcus equi, age at onset of pneumonia, and minimum inhibitory concentration (MIC) of azithromycin for R equi isolates cultured from fecal and clinical samples. DESIGN: Controlled, randomized clinical trial. ANIMALS: 338 foals born and raised at 10 equine breeding farms; each farm had a history of endemic R equi infections. PROCEDURES: Group 1 foals were control foals, and group 2 foals were treated with azithromycin (10 mg/kg [4.5 mg/lb], PO, q 48 h) during the first 2 weeks after birth. Foals were monitored for development of pneumonia attributable to R equi infection and for adverse effects of azithromycin. Isolates of R equi were tested for susceptibility to azithromycin. RESULTS: The proportion of R equi-affected foals was significantly higher for control foals (20.8%) than for azithromycin-treated foals (5.3%). Adverse effects of azithromycin treatment were not detected, and there were no significant differences between groups for the MICs of azithromycin for R equi isolates cultured from fecal or clinical samples. CONCLUSIONS AND CLINICAL RELEVANCE: Azithromycin chemoprophylaxis effectively reduced the cumulative incidence of pneumonia attributable to R equi among foals at breeding farms with endemic R equi infections. There was no evidence of resistance to azithromycin. Nonetheless, caution must be used because it is possible that resistance could develop with widespread use of azithromycin as a preventative treatment. Further investigation is needed before azithromycin chemoprophylaxis can be recommended for control of R equi infections.

The etiology of community-acquired pneumonia in Australia: why penicillin plus doxycycline or a macrolide is the most appropriate therapy.

BACKGROUND: Available data on the etiology of community-acquired pneumonia (CAP) in Australia are very limited. Local treatment guidelines promote the use of combination therapy with agents such as penicillin or amoxycillin combined with either doxycycline or a macrolide. METHODS: The Australian CAP Study (ACAPS) was a prospective, multicenter study of 885 episodes of CAP in which all patients underwent detailed assessment for bacterial and viral pathogens (cultures, urinary antigen testing, serological methods, and polymerase chain reaction). Antibiotic agents and relevant clinical outcomes were recorded. RESULTS: The etiology was identified in 404 (45.6%) of 885 episodes, with the most frequent causes being Streptococcus pneumoniae (14%), Mycoplasma pneumoniae (9%), and respiratory viruses (15%; influenza, picornavirus, respiratory syncytial virus, parainfluenza virus, and adenovirus). Antibiotic-resistant pathogens were rare: only 5.4% of patients had an infection for which therapy with penicillin plus doxycycline would potentially fail. Concordance with local antibiotic recommendations was high (82.4%), with the most commonly prescribed regimens being a penicillin plus either doxycycline or a macrolide (55.8%) or ceftriaxone plus either doxycycline or a macrolide (36.8%). The 30-day mortality rate was 5.6% (50 of 885 episodes), and mechanical ventilation or vasopressor support were required in 94 episodes (10.6%). Outcomes were not compromised by receipt of narrower-spectrum beta-lactams, and they did not differ on the basis of whether a pathogen was identified. CONCLUSIONS: The vast majority of patients with CAP can be treated successfully with narrow-spectrum beta-lactam treatment, such as penicillin combined with doxycycline or a macrolide. Greater use of such therapy could potentially reduce the emergence of antibiotic resistance among common bacterial pathogens.

Haemophilus influenzae type-b and non-b-type invasive diseases in urban children (<5years) of Bangladesh: implications for therapy and vaccination.

OBJECTIVE: To prospectively study the epidemiology and antibiotic resistance of Haemophilus infuenzae isolates from invasive infections in children. METHODS: Children (<5years) with pneumonia, meningitis and septicemia from three hospitals in Dhaka, Bangladesh were enrolled (1999-2003); clinical and laboratory data, and blood for cultures were collected. Cerebrospinal fluid (CSF) of meningitis cases was analyzed (Gram stain, culture and biochemical tests). Hib antigen was detected by latex agglutination (LA) in culture-negative pyogenic CSF and PCR was done for bexA gene in culture- and LA-negative pyogenic CSF. Antibiotic susceptibility was determined by E-Tests and beta-lactamase by nitrocefin stick. RESULTS: Seventy-three cases of H. influenzae infections (46 of 293 meningitis cases, 25 of 1493 pneumonia cases, 2 of 48 septicemia cases) were detected; 63%, 34% and 3% of them had meningitis, pneumonia and septicemia respectively. H. influenzae type b (Hib) caused infections in 80.8% of cases (60.3% meningitis, 20.5% pneumonia). Most (86%) infections clustered in 4-12month infants. The case-fatality in pneumonia was 8% compared to 19% in meningitis. H. influenzae isolates from pneumonia and meningitis children were equally resistant to antibiotics (46% vs 43%). Of 10 drugs tested, isolates were resistant to ampicillin (31%), chloramphenicol (42%), trimethoprim-sulfamethoxazole (44%) and azithromycin (1.4%). Multidrug-resistant (MDR) strains were equally prevalent in Hib (31%) and non-b-type (29%) isolates, and in pneumonia (31%) and meningitis (34%) cases. None was resistant to amoxicillin-clavulanate, ceftriaxone, ciprofloxacin, levofloxacin, moxifloxacin, and gatifloxacin. Of all H. influenzae infections, 40%, 4.4% and 100% of pneumonia, meningitis and septicemia cases were caused by other serotypes or non-typeable strains. All ampicillin-resistant-strains produced beta-lactamase without detection of beta-lactamase-negative-ampicillin-resistant (BLNAR) strains. CONCLUSION: Hib is a leading cause of invasive bacterial infections in infants. Multidrug-resistant H. influenzae is common and requires amoxicillin-clavulanate, ceftriaxone or azithromycin as empirical therapy with specific recommendation for use of ceftriaxone for treatment of meningitis particularly MDR cases. New fluoroquinolines has potential utility. An effective national Hib vaccination programme is essential in Bangladesh although non-Hib infections will remain an issue.