Microbiological diagnostic performance of metagenomic next-generation sequencing compared with conventional culture for patients with community-acquired pneumonia.

Background: Community-acquired pneumonia (CAP) is an extraordinarily heterogeneous illness, both in the range of responsible pathogens and the host response. Metagenomic next-generation sequencing (mNGS) is a promising technology for pathogen detection. However, the clinical application of mNGS for pathogen detection remains challenging. Methods: A total of 205 patients with CAP admitted to the intensive care unit were recruited, and broncho alveolar lavage fluids (BALFs) from 83 patients, sputum samples from 33 cases, and blood from 89 cases were collected for pathogen detection by mNGS. At the same time, multiple samples of each patient were tested by culture. The diagnostic performance was compared between mNGS and culture for pathogen detection. Results: The positive rate of pathogen detection by mNGS in BALF and sputum samples was 89.2% and 97.0%, which was significantly higher (P < 0.001) than that (67.4%) of blood samples. The positive rate of mNGS was significantly higher than that of culture (81.0% vs. 56.1%, P = 1.052e-07). A group of pathogens including Mycobacterium abscessus, Chlamydia psittaci, Pneumocystis jirovecii, Orientia tsutsugamushi, and all viruses were only detected by mNGS. Based on mNGS results, Escherichia coli was the most common pathogen (15/61, 24.59%) of non-severe patients with CAP, and Mycobacterium tuberculosis was the most common pathogen (21/144, 14.58%) leading to severe pneumonia. Pneumocystis jirovecii was the most common pathogen (26.09%) in severe CAP patients with an immunocompromised status, which was all detected by mNGS only. Conclusion: mNGS has higher overall sensitivity for pathogen detection than culture, BALF, and sputum mNGS are more sensitive than blood mNGS. mNGS is a necessary supplement of conventional microbiological tests for the pathogen detection of pulmonary infection.

Clinical characteristics and pathogen analysis of bronchoalveolar lavage fluid in elderly patients with community-acquired pneumonia.

OBJECTIVE: To analyze the clinical characteristics and bronchoalveolar lavage fluid pathogens in elderly patients with community-acquired pneumonia (CAP). METHODS: This was a retrospective observational epidemiological study using that elderly cases diagnosed with community-acquired pneumonia receiving treatment at the Affiliated Hospital of North China University of Technology, Tangshan Hongci Hospital and Tangshan Fengnan District Hospital of Traditional Chinese Medicine. A total of 92 cases were divided into two groups according to age. There were 44 patients over 75-year-old and 48 patients between 65 and 74-year-old. RESULTS: Compared with the elderly 65 to 74-year-old, the elderly over 75-year-old with diabetes are more likely to suffer from CAP (35.42% vs. 63.64%, p = 0.007) and are more likely to have mixed infections (6.25% vs. 22.73%, p = 0.023) or larger lesions (45.83% vs. 68.18%, p = 0.031). Their hospital stays will also be extended (39.58% vs. 63.64%, p = 0.020), and the albumin level (37.51 ± 8.92 vs. 30.93 ± 6.58, p = 0.000), the neutrophils level (9.09(6.26-10.63) vs. 7.18(5.35-9.17),p = 0.026) is significantly lower and the d-dimer (505.42 ± 197.12 vs. 611.82 ± 195.85, p = 0.011), PCT (0.08 ± 0.04 vs. 0.12 ± 0.07, p = 0.001) levels are significantly higher. CONCLUSION: The clinical symptoms and signs of elderly CAP patients are not so typical, and the infection is more serious. Attention should therefore be paid to elderly patients. Hypoalbuminemia and high d-dimer can predict the prognosis of patients.

Vitamin D as an adjunct to antibiotics for the treatment of acute childhood pneumonia.

BACKGROUND: Children with acute pneumonia may be vitamin D deficient. Clinical trials have found that prophylactic vitamin D supplementation decreases children's risk of developing pneumonia. Data on the therapeutic effects of vitamin D in acute childhood pneumonia are limited. This is an update of a Cochrane Review first published in 2018. OBJECTIVES: To evaluate the efficacy and safety of vitamin D supplementation as an adjunct to antibiotics for the treatment of acute childhood pneumonia. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, and two trial registries on 28 December 2021. We applied no language restrictions. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that compared vitamin D supplementation with placebo in children (aged one month to five years) hospitalised with acute community-acquired pneumonia, as defined by the World Health Organization (WHO) acute respiratory infection guidelines. For this update, we reappraised eligible trials according to research integrity criteria, excluding RCTs published from April 2018 that were not prospectively registered in a trials registry according to WHO or Clinical Trials Registry - India (CTRI) guidelines (it was not mandatory to register clinical trials in India before April 2018). DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion and extracted data. For dichotomous data, we extracted the number of participants experiencing the outcome and the total number of participants in each treatment group. For continuous data, we used the arithmetic mean and standard deviation (SD) for each treatment group together with number of participants in each group. We used standard methodological procedures expected by Cochrane. MAIN RESULTS: In this update, we included three new trials involving 468 children, bringing the total number of trials to seven, with 1601 children (631 with pneumonia and 970 with severe or very severe pneumonia). We categorised three previously included studies and three new studies as 'awaiting classification' based on the research integrity screen. Five trials used a single bolus dose of vitamin D (300,000 IU in one trial and 100,000 IU in four trials) at the onset of illness or within 24 hours of hospital admission; one used a daily dose of oral vitamin D (1000 IU for children aged up to one year and 2000 IU for children aged over one year) for five days; and one used variable doses (on day 1, 20,000 IU in children younger than six months, 50,000 IU in children aged six to 12 months, and 100,000 IU in children aged 13 to 59 months; followed by 10,000 IU/day for four days or until discharge). Three trials performed microbiological diagnosis of pneumonia, radiological diagnosis of pneumonia, or both. Vitamin D probably has little or no effect on the time to resolution of acute illness (mean difference (MD) -1.28 hours, 95% confidence interval (CI) -5.47 to 2.91; 5 trials, 1188 children; moderate-certainty evidence). We do not know if vitamin D has an effect on the duration of hospitalisation (MD 4.96 hours, 95% CI -8.28 to 18.21; 5 trials, 1023 children; very low-certainty evidence). We do not know if vitamin D has an effect on mortality rate (risk ratio (RR) 0.69, 95% CI 0.44 to 1.07; 3 trials, 584 children; low-certainty evidence). The trials reported no major adverse events. According to GRADE criteria, the evidence was of very low-to-moderate certainty for all outcomes, owing to serious trial limitations, inconsistency, indirectness, and imprecision. Three trials received funding: one from the New Zealand Aid Corporation, one from an institutional grant, and one from multigovernment organisations (Bangladesh, Sweden, and UK). The remaining four trials were unfunded. AUTHORS' CONCLUSIONS: Based on the available evidence, we are uncertain whether vitamin D supplementation has important effects on outcomes of acute pneumonia when used as an adjunct to antibiotics. The trials reported no major adverse events. Uncertainty in the evidence is due to imprecision, risk of bias, inconsistency, and indirectness.

Of onions and men: Report of cavitary community acquired pneumonia due to Burkholderia cepacia complex in an immunocompetent patient and review of the literature.

Burkholderia cepacia complex consists of highly antibiotic resistant gram negative bacilli that are plant symbionts and also potential agents of human infection.  This bacterial family's claim to fame in clinical medicine is as the scourge of cystic fibrosis patients, in whom it is a notorious respiratory pathogen.  Outside of cystic fibrosis, it rarely comes to mind as an etiology of community acquired pneumonia with or without lung cavitation in immunocompetent hosts.  We describe a case of an otherwise healthy, community-dwelling man who presented with subacute cavitary lung disease, the causative organism of which turned out to be Burkholderia cepacia complex.  Our report is accompanied by a review of the literature, which identified an additional eleven cases in the same category.  We analyze all of the available cases for the emergence of any identifiable patterns or peculiarities.

Blind Spots of Traditional Microbiological Tests for Severe Community-Acquired Pneumonia in Adults and Availability of Nonculture Techniques: A Nationwide Survey of Physicians in China.

BACKGROUND: In China, no national survey has been conducted to evaluate physicians' attitudes and compliance with guidelines in the management of adult patients with community-acquired pneumonia (CAP). Therefore, this study aimed to evaluate physicians' awareness of the use of microbiological tests in the management of severe CAP (SCAP) and to investigate the availability of nonculture tests in China. METHODS: A nationwide electronic questionnaire survey was conducted among Chinese physicians between March and July 2018, which assessed their viewpoints concerning the issues in the management of SCAP. RESULTS: A total of 6333 physicians completed this survey, evenly covering all career stages. Among these, 3208 (50.6%) and 1936 (30.6%) had blind spots in the application of blood and sputum cultures in the management of SCAP, respectively. Nonteaching hospital, nonrespirologists, and junior career stage were independently associated with misunderstandings. Regarding nonculture methods, 52.7% of the facilities had no access to polymerase chain reaction-based pathogen detection tests. The accessibility of urinary antigen tests for Streptococcus pneumoniae (42.5%) and Legionella pneumophila (38.5%) was also low. The main barriers were inland and remote region, lower hospital level, and nonteaching hospital. CONCLUSIONS: Insufficient use of sputum and blood cultures, together with low accessibility of major nonculture techniques, were noticeable barriers to achieving microbiological diagnosis of SCAP in China. To help curb the overuse of broad-spectrum antibiotics, further measures should be taken to raise awareness among nonspecialists and promote rapid nonculture tests, especially in nonteaching hospitals and developing regions.

Serum metabolite profiles as potential biochemical markers in young adults with community-acquired pneumonia cured by moxifloxacin therapy.

Despite the utilization of various biochemical markers and probability calculation algorithms based on clinical studies of community-acquired pneumonia (CAP), more specific and practical biochemical markers remain to be found for improved diagnosis and prognosis. In this study, we aimed to detect the alteration of metabolite profiles, explore the correlation between serum metabolites and inflammatory markers, and seek potential biomarkers for young adults with CAP. 13 Eligible young mild CAP patients between the ages of 18 and 30 years old with CURB65 = 0 admitted to the respiratory medical department were enrolled, along with 36 healthy participants as control. Untargeted metabolomics profiling was performed and metabolites including alcohols, amino acids, carbohydrates, fatty acids, etc. were detected. A total of 227 serum metabolites were detected. L-Alanine, 2-Hydroxybutyric acid, Methylcysteine, L-Phenylalanine, Aminoadipic acid, L-Tryptophan, Rhamnose, Palmitoleic acid, Decanoylcarnitine, 2-Hydroxy-3-methylbutyric acid and Oxoglutaric acid were found to be significantly altered, which were enriched mainly in propanoate and tryptophan metabolism, as well as antibiotic-associated pathways. Aminoadipic acid was found to be significantly correlated with CRP levels and 2-Hydroxy-3-methylbutyric acid and Palmitoleic acid with PCT levels. The top 3 metabolites of diagnostic values are 2-Hydroxybutyric acid(AUC = 0.90), Methylcysteine(AUC = 0.85), and L-Alanine(AUC = 0.84). The AUC for CRP and PCT are 0.93 and 0.91 respectively. Altered metabolites were correlated with inflammation severity and were of great diagnostic value for CAP.

Outcomes of Empirical Antimicrobial Therapy for Pediatric Community-onset Febrile Urinary Tract Infection in the Era of Increasing Antimicrobial Resistance.

BACKGROUND: Urinary tract infection (UTI) is a common cause of fever in children. Despite the increasing numbers of extended-spectrum beta-lactamase-producing organisms in the community, the empirical therapy of choice is still third-generation cephalosporins. This study was performed to investigate whether inappropriate empirical therapy (IAT) of community-onset UTI results in adverse clinical outcomes. METHODS: We retrospectively studied a cohort of pediatric patients with first-episode community-onset UTI caused by Escherichia coli, Klebsiella pneumoniae and Proteus spp. at Ramathibodi Hospital from 2011 to 2017. The patients were classified into IAT and appropriate empirical therapy (AT) groups. Medical records were reviewed to assess clinical outcomes. RESULTS: One hundred fifty-one eligible patients were enrolled in this study. The most common causative organism was E. coli (88.8% and 96.2% in the AT and IAT groups, respectively). Among the causative organisms, 19.8% were extended-spectrum beta-lactamase-producing organisms. There was no significant difference in clinical failure, microbiologic failure, relapse or time to defervescence between the 2 groups. No patients in either group developed sepsis after receiving empirical therapy. However, the length of hospital stay was significantly longer in the IAT than AT group [4.00 (4.50-6.00) vs. 7.00 (5.00-11.25) days, respectively; P = 0.000]. CONCLUSIONS: No significant difference in treatment outcomes was found between pediatric patients receiving AT and IAT for the treatment of UTI. In the era of increasing antimicrobial resistance, third-generation cephalosporins may still be a good choice as an empirical antimicrobial for children diagnosed with community-onset UTI.

Successful treatment with daptomycin and ceftaroline of MDR Staphylococcus aureus native valve endocarditis: a case report.

OBJECTIVES: The best therapeutic approach for treating MRSA endocarditis remains unknown, particularly in cases of high vancomycin MICs. We report here a case of daptomycin-non-susceptible, ceftaroline-resistant and fosfomycin-resistant MRSA native left valve endocarditis that was successfully treated with valve repair and a combination of high-dose daptomycin and ceftaroline. METHODS: Antimicrobial testing of the clinical strain was performed using Etest and microdilution broth methods. Time-kill and chequerboard methodologies were used to test the activity of antibiotic combinations. RESULTS: By Etest, the MIC of vancomycin was 2 mg/L, the MIC of daptomycin was 2 mg/L, the MIC of fosfomycin was 1024 mg/L and the MIC of ceftaroline was 1.5 mg/L. At the standard inoculum (105 cfu/mL), the three combinations of daptomycin plus ceftaroline, cloxacillin or fosfomycin were synergistic and bactericidal. However, when these combinations were tested using a higher inoculum (108 cfu/mL), all combinations were synergistic, but only daptomycin plus ceftaroline had bactericidal activity. CONCLUSIONS: These results confirmed a synergistic effect between daptomycin plus ceftaroline and increased bactericidal activity against MRSA, suggesting that this combination may be effective for the treatment of invasive MRSA infection. Our experience highlights the potential clinical use of synergy testing to guide difficult treatment decisions in patients with MDR MRSA infection.

Outbreak of mycoplasmal round pneumonia in an adult population: A case series.

BACKGROUND: Mycoplasmal pneumonia is a common type of adult community-acquired pneumonia in China, but round/spherical pneumonia caused by mycoplasma pneumoniae has rarely been reported. Here, we report an outbreak of mycoplasmal round pneumonia in a military dormitory in China. METHODS: We analysed epidemiological, clinical, imaging and laboratory data from a series of adults affected by an outbreak of mycoplasmal round pneumonia in the dormitory of a military hospital (Fuzhou General Hospital) in Fuzhou, China. The dormitory included 2 separate buildings. Mycoplasma antibody was detected using a passive agglutination assay. RESULTS: The first case in our series, a 23-year-old male intern, presented on July 16, 2015 with a 3-day history of low-grade fever, dizziness, fatigue and chest tightness. Chest computed tomography revealed spherical masses. Over the following 4 days, 11 individuals who had been in close contact with the first patient were found to have similar masses. All 12 cases were mildly symptomatic or asymptomatic, and fever was the only sign visible upon physical examination. Chest radiology revealed single, round consolidations in 3 cases and multiple round consolidations in 9 cases; consolidations ranged in size from 0.2 to 2.9 cm. Most cases had normal blood cell count, erythrocyte sedimentation rate and C reactive protein level. Nasopharyngeal swabs from all cases tested negative for 25 pathogens, including Mycoplasma pneumoniae, in a PCR-based assay performed on August 1, 2015. All 12 patients showed a 4-fold increase in the titre of anti-mycoplasmal pneumonia antibody in paired sera on August 13, 2015. Patients were given the antibiotic moxifloxacin or symptomatic treatment, and 11 of the 12 cases showed complete resolution of round pneumonia lesions within 4 weeks. CONCLUSION: This case series illustrates the diversity of clinical manifestations as well as imaging findings for mycoplasmal pneumonia, to which clinicians should pay more attention. Mycoplasmal round pneumonia should be included in differential diagnosis of multiple pulmonary nodules in adults in order to enable accurate clinical identification of disease and successful treatment and resolution.

Short-course antimicrobial therapy for paediatric respiratory infections (SAFER): study protocol for a randomized controlled trial.

BACKGROUND: Community-acquired pneumonia (CAP) is commonly diagnosed in children. The Infectious Disease Society of America guidelines recommend 10 days of high-dose amoxicillin for the treatment of non-severe CAP but 5-day "short course" therapy may be just as effective. Randomized trials in adults have already demonstrated non-inferiority of 5-day short-course treatment for adults hospitalized with severe CAP and for adults with mild CAP treated as outpatients. Minimizing exposure to antimicrobials is desirable to avoid harms including diarrhoea, rashes, severe allergic reactions, increased circulating antimicrobial resistance, and microbiome disruption. METHODS: The objective of this multicentre, randomized, non-inferiority, controlled trial is to investigate whether 5 days of high-dose amoxicillin is associated with lower rates of clinical cure 14-21 days later as compared to 10 days of high-dose amoxicillin, the reference standard. Recruitment and enrolment will occur in the emergency departments of McMaster Children's Hospital and the Children's Hospital of Eastern Ontario. All children in the study will receive 5 days of amoxicillin after which point they will receive either 5 days of a different formulation of amoxicillin or a placebo. Assuming a clinical failure rate of 5% in the reference arm, a non-inferiority margin of 7.5%, one-sided alpha set at 0.025 and power of 0.80, 270 participants will be required. Participants from a previous feasibility study (n = 60) will be rolled over into the current study. We will be performing multiplex respiratory virus molecular testing, quantification of nasopharyngeal pneumococcal genomic loads, salivary inflammatory marker testing, and faecal microbiome profiling on participants. DISCUSSION: This is a pragmatic study seeking to provide high-quality evidence for front-line physicians evaluating children presenting with mild CAP in North American emergency departments in the post-13-valent pneumococcal, conjugate vaccine era. High-quality evidence supporting the non-inferiority of short-course therapy for non-severe paediatric CAP should be generated prior to making changes to established guidelines. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02380352 . Registered on 2 March 2015.

[Analysis of the efficiency of antimicrobial treatment for community-acquired pneumonia in clinical practice]. / Analiz éffektivnosti antimikrobnoi terapii vnebol'nichnoi pnevmonii v klinicheskoi praktike.

AIM: To analyze actual drug consumption based on the defined daily dose (DDD analysis) and to analyze the utilization of drugs based on their proportion of the total defined daily doses (DU90% analysis) for the antimicrobial therapy of community-acquired pneumonia (CAP) in clinical practice at a hospital in Russia. MATERIAL AND METHODS: The investigation materials were the data of 117 case histories of male (51.3%) and female (48.7%) patients hospitalized with CAP at Nizhny Novgorod City Clinical Hospital Five in 2015. The investigation enrolled all the patients admitted to the hospital over the analyzed period. DDD analysis and DU90% analysis were used as study methods. RESULTS: DDD analysis and DU90% analysis of antimicrobial therapy for CAP were carried out at the hospital in clinical practice during a year. The annual number of defined daily doses (NDDD) for antimicrobial drugs, the number of defined daily doses per 100 bed-days (NDDD/100 bed-days), and a drug load (g) per 1000 CAP patients per day and per CAP patient per year were determined. The largest NDDD/year for CAP treatment with ceftriaxone was 376 g, or 43.43 NDDD/100 bed-days, which is much higher than that with other antimicrobial agents. The daily drug load of ceftriaxone per 1,000 CAP patients was 8.8 g, which exceeds that of moxifloxacin by 18.7 times, azithromycin and levofloxacin by 5 times, and ampicillin/sulbactam by 2.3 times. The daily drug load of ceftriaxone per CAP patient was 3.2 g, which exceeds that of of ampicillin/sulbactam by 2.3 times, levofloxacin and azithromycin by 5 times, and moxifloxacin by 19 times. CONCLUSION: It may be recommended that the proportion of cephalosporins as drugs that promote the rise of resistance in microbes and their production of extended-spectrum ß-lactamases should be further limited, the proportion of penicillins be extended, and the administered ampicillin/sulbactam be added, for example, by amoxicillin/clavulanate. Penicillins contribute to the rise of resistance to a lesser degree, and the use of two different penicillin molecules specified in the guidelines for the treatment of CAP will be able to slow the process further. By the same reasoning, it is also advisable to use cefuroxime (second-generation cephalosporins) along with ceftriaxone in patients in stable condition, without impairing vital functions.

[Methodological quality assessment of community-acquired pneumonia clinical practice guidelines in China based on AGREE â ¡ tool].

This study is aimed to identify and assess the methodological quality of community-acquired pneumonia (CAP) clinical practice guidelines (CPG) in China by using AGREE Ⅱ tool. CNKI, SinoMed, Wanfang, and VIP Chinese databases from database establishment to March 2017 were searched by manual retrieval to collect all the clinical practice guidelines prepared by various associations or organizations, then AGREE Ⅱtool was used to assess them. Data in each CPG were analyzed in terms of six domains, including scope and purpose, participants, rigor, clarity and readability, applicability and editorial independence. A total of 4 CPGs were included. The results showed that the scope and purpose scored 45.8%; the clarity of expression scored 44.75%; the participants scored 31.9%; the rigor scored 18.98%; the applicability scored 7%; and finally the editorial independence scored 1%. It is concluded that the quality of applicability and the editorial independence should attained paid more attention in future development or updating of the guidelines. In addition to strengthening the compliance with international general principles, we should also pay attention to the characteristics of traditional Chinese medicine treatment, especially the related evidences as complementary and alternative treatment for western intervention measures.

Clinical Pathway and Monthly Feedback Improve Adherence to Antibiotic Guideline Recommendations for Community-Acquired Pneumonia.

BACKGROUND: Compliance with community-acquired pneumonia (CAP) guidelines remains poor despite a substantial body of evidence indicating that guideline-concordant care improves patient outcomes. The aim of this study was to compare the relative effectiveness of a general educational and a targeted emergency department intervention on improving physicians' concordance with CAP guidelines. METHODS: Two distinct interventions were implemented over specific time periods. The first intervention was educational, focusing on the development of local CAP guidelines and their dissemination through hospital-wide educational programmes. The second intervention was a targeted one for the emergency department, where a clinical pathway for the initial management of CAP patients was introduced, followed by monthly feedback to the emergency department (ED) physicians about concordance rates with the guidelines. Data on the concordance rate to CAP guidelines was collected from a retrospective chart review. RESULTS: A total of 398 eligible patient records were reviewed to measure concordance to CAP guidelines over the study period. Concordance rates during the baseline and educational intervention periods were similar (28.1% vs. 31.2%; p > 0.05). Significantly more patients were treated in accordance with the CAP guidelines after the ED focused intervention when compared to the baseline (61.5% vs. 28.1%; p < 0.05) or educational period (61.5% vs. 31.2%; p < 0.05). CONCLUSIONS: A targeted intervention with a CAP clinical pathway and monthly feedback was a successful strategy to increase adherence to empirical antibiotic recommendations in CAP guidelines.

SOLITAIRE-IV: A Randomized, Double-Blind, Multicenter Study Comparing the Efficacy and Safety of Intravenous-to-Oral Solithromycin to Intravenous-to-Oral Moxifloxacin for Treatment of Community-Acquired Bacterial Pneumonia.

BACKGROUND: Solithromycin, a novel macrolide antibiotic with both intravenous and oral formulations dosed once daily, has completed 2 global phase 3 trials for treatment of community-acquired bacterial pneumonia. METHODS: A total of 863 adults with community-acquired bacterial pneumonia (Pneumonia Outcomes Research Team [PORT] class II-IV) were randomized 1:1 to receive either intravenous-to-oral solithromycin or moxifloxacin for 7 once-daily doses. All patients received 400 mg intravenously on day 1 and were permitted to switch to oral dosing when clinically indicated. The primary objective was to demonstrate noninferiority (10% margin) of solithromycin to moxifloxacin in achievement of early clinical response (ECR) assessed 3 days after first dose in the intent-to-treat (ITT) population. Secondary endpoints included demonstrating noninferiority in ECR in the microbiological ITT population (micro-ITT) and determination of investigator-assessed success rates at the short-term follow-up (SFU) visit 5-10 days posttherapy. RESULTS: In the ITT population, 79.3% of solithromycin patients and 79.7% of moxifloxacin patients achieved ECR (treatment difference, -0.46; 95% confidence interval [CI], -6.1 to 5.2). In the micro-ITT population, 80.3% of solithromycin patients and 79.1% of moxifloxacin patients achieved ECR (treatment difference, 1.26; 95% CI, -8.1 to 10.6). In the ITT population, 84.6% of solithromycin patients and 88.6% of moxifloxacin patients achieved clinical success at SFU based on investigator assessment. Mostly mild/moderate infusion events led to higher incidence of adverse events overall in the solithromycin group. Other adverse events were comparable between treatment groups. CONCLUSIONS: Intravenous-to-oral solithromycin was noninferior to intravenous-to-oral moxifloxacin. Solithromycin has potential to provide an intravenous and oral option for monotherapy for community-acquired bacterial pneumonia. CLINICAL TRIALS REGISTRATION: NCT01968733.

Community-associated Staphylococcus aureus pneumonia among Greek children: epidemiology, molecular characteristics, treatment, and outcome.

Staphylococcus aureus is an infrequent cause of community-associated (CA-SA) pneumonia in children. The aim of this study was to evaluate the clinical, epidemiological, microbiological, and molecular characteristics of CA-SA pneumonia among children hospitalized in two large tertiary care referral centers during an 8-year period. Cases of CA-SA pneumonia admitted between 2007 and 2014 were retrospectively examined through medical record review. Molecular investigation was performed for available strains; mecA, Panton-Valentine leukocidin (PVL) (lukS-lukF-PV), and fibronectin binding protein A (fnbA) genes were detected by polymerase chain reaction (PCR). Clones were assigned by agr groups, pulsed-field gel electrophoresis (PFGE), SCCmec, and multilocus sequencing typing (MLST). In total, 41 cases were recorded (boys, 61 %), with a median age of 4.3 months (range, 1-175). Methicillin-resistant S. aureus (MRSA) accounted for 31 cases (75.6 %). Complications included empyema (25/41, 61 %), pneumatoceles (7/41, 17 %), and lung abscess (1/41, 2.5 %). Intensive care unit (ICU) admission was required in 58.5 %. Two deaths occurred (4.9 %). Definitive therapy was based on vancomycin with or without other antibiotics (55.9 %), followed by clindamycin and linezolid (26.5 % each). All isolates were susceptible to vancomycin (MIC90 2 mg/L, range 1-2), teicoplanin, and linezolid, whereas 26.8 % were resistant to clindamycin. Among the 25 studied strains, 20 were mecA-positive (MRSA), carrying also the fnbA gene. Of these, 90 % belonged to the ST80-IV/agr3/PVL-positive clone. Methicillin-susceptible S. aureus (MSSA) strains showed polyclonality, 3/5 were PVL-positive, and 3/5 were fnbA-positive. MRSA and particularly the ST80-IV clone predominated among staphylococcal pneumonia cases in children. Treatment provided was effective in all but two patients, despite the relatively high minimum inhibitory concentration (MIC) of vancomycin and a high resistance to clindamycin.

Rapid detection of amoxicillin-susceptible Escherichia coli in fresh uncultured urine: a new tool to limit the use of broad-spectrum empirical therapy of community-acquired pyelonephritis.

Because of the high prevalence of amoxicillin resistance among uropathogens, amoxicillin is not recommended as an empirical treatment of urinary tract infections (UTIs). Quick detection of an amoxicillin-susceptible Escherichia coli (ASEC) would allow prescribing amoxicillin without preliminary broad-spectrum empirical treatment in uncomplicated pyelonephritis. To quickly diagnose UTIs due to ASEC, we developed a real-time PCR that detects in fresh uncultured urine the E. coli-specific gene yccT as well as the blaTEM and blaCTX-M genes. The ASEC rapid test was considered positive if the PCR was positive for the yccT gene but negative for blaTEM and blaCTX-M. The test was compared with culture and susceptibility testing. Among 200 patients with a suspected community-acquired UTI, 61 (30.5%) had a monobacterial UTI due to ASEC. The ASEC rapid test result was obtained in 3 h 13 [95% confidence interval (CI) 3 h 12-3 h 15] and was positive for 43 patients (21.5%). Specificity and sensitivity were 97.8% (95% CI 95.8-99.8%) and 65.6% (95% CI 59.0-72.1%), respectively. Positive and negative predictive values were 93.0% (95% CI 89.5-96.5%) and 86.6% (95% CI 81.9-91.3%), respectively. Owing to its high specificity and positive predictive value, the ASEC rapid test allows the diagnosis of UTI due to ASEC only 3 h after urine sampling. A positive ASEC rapid test may be used to treat uncomplicated pyelonephritis with amoxicillin from the start, without preliminary broad-spectrum empirical treatment. The ASEC rapid test is a promising tool to spare fluoroquinolones and third-generation cephalosporins in UTIs.

Efficacy of zinc sulphate on in-hospital outcome of community-acquired pneumonia in people aged 50 years and over.

SETTING: Some studies have reported a beneficial effect of zinc sulphate in children with community-acquired pneumonia (CAP). OBJECTIVE: To evaluate the effect of adjuvant zinc therapy in adult hospitalised CAP patients aged ⩾50 years on standard antibiotic treatment. METHODS: In a randomised double-blind placebo-controlled clinical trial, 91 hospitalised patients diagnosed with CAP using standard clinical and radiological criteria were randomised to receive 220 mg (110 mg twice daily) zinc sulphate for 4 days or placebo, in addition to antibiotics. The primary endpoint was length of hospital stay, and secondary endpoints were time to normalisation of oxygen saturation, respiratory rate and temperature. Disease severity was scored using CURB-65 (mental Confusion, Urea >20 mg/dl, Respiratory rate ⩾30/min, low Blood pressure and age ⩾65 years) RESULTS: The results did not show significant differences in length of hospital stay, time to normalisation of respiratory rate and oxygen saturation between patients in the zinc sulphate and placebo groups (P = 0.18, 0.65 and 0.26, respectively). CONCLUSION: A short course of zinc supplementation does not improve outcome in hospitalised patients aged ⩾50 years with CAP. In this setting, it should not be recommended as routine adjunctive treatment.

Use of cefuroxime for women with community-onset acute pyelonephritis caused by cefuroxime-susceptible or -resistant Escherichia coli.

BACKGROUND/AIMS: Efforts to decrease the use of extended-spectrum cephalosporins are required to prevent the selection and transmission of multi-drug resistant pathogens, such as extended-spectrum ß-lactamase (ESBL)-producing Enterobacteriaceae. The objectives of this study were to assess the clinical efficacy of intravenous cefuroxime as an empirical antibiotic for the treatment of hospitalized women with acute pyelonephritis (APN) caused by Escherichia coli. METHODS: We analyzed the clinical and microbiologic database of 328 hospitalized women with community-onset APN. RESULTS: Of 328 women with APN, 22 patients had cefuroxime-resistant E. coli APN, and 306 patients had cefuroxime-susceptible E. coli APN. The early clinical success rates were significantly higher (p = 0.001) in the cefuroxime-susceptible group (90.8%, 278/306) than in the cefuroxime-resistant group (68.2%, 15/22) at 72 hours. The clinical cure rates at 4 to 14 days after completing antimicrobial therapy were not significantly different in the cefuroxime-resistant or -susceptible groups, with 88.2% (15/17) and 97.8% (223/228; p = 0.078), respectively. The microbiological cure rates were not significantly different and were 90.9% (10/11) and 93.4% (128/137), respectively (p = 0.550). The median duration of hospitalization in the cefuroxime-resistant and -susceptible groups was 10 days (interquartile range [IQR], 8 to 13) and 10 days (IQR, 8 to 14), respectively (p =0.319). CONCLUSIONS: Cefuroxime, a second-generation cephalosporin, can be used for the initial empirical therapy of community-onset APN if tailored according to uropathogen identification and susceptibility results, especially in areas where the prevalence rate of ESBL-producing uropathogens is low.

Microbiology and resistance in first episodes of spontaneous bacterial peritonitis: implications for management and prognosis.

PURPOSE: International guidelines for antibiotic treatment of spontaneous bacterial peritonitis (SBP) are based on studies conducted decades ago and do not reflect regional differences of bacterial epidemiology. METHODS: We retrospectively analyzed epidemiology of agents, antibiotic resistance patterns, and survival in liver cirrhosis patients with their first episode of SBP during the years 2007-2013. RESULTS: Of the 311 patients included, 114 patients had a positive ascites culture, and 197 had an ascitic neutrophil count >250 µL. Gram-positive bacteria (47.8%) were more frequently found than Gram-negatives (44.9%), fungi in 7.2%. Enterobacter spp. (40.6%), Enterococcus spp. (26.1%), and Staphylcoccus spp. (13.8%) were the most frequently isolated agents. Third-generation cephalosporins covered 70.2% of non-nosocomial and 56.3% of nosocomial-acquired SBP cases.When SBP was diagnosed by a positive ascitic culture, survival was highly significantly reduced (mean: 13.9 ± 2.9 months; 95% confidence interval [CI]: 8.1-19.8) compared with culture-negative SBP patients (mean: 44.1 ± 5.4 months; 95% CI: 33.4-54.9; P = 0.000). Along with model of end-stage liver disease score and intensive care unit contact, a positive ascites culture remained an independent risk factor associated with poor survival (odds ratio: 1.49; 95% CI: 1.09-2.03) in multivariate analysis; piperacillin/tazobactam proved to be an adequate antibiotic for nosocomial and non-nosocomial SBP in 85.1% and 92.5%, respectively. SBP infection with Enterococcus spp. was associated with poor patient survival (P = 0.048). CONCLUSIONS: Third-generation cephalosporins have poor microbial coverage for treatment of SBP. Current guidelines need to adapt for the emerging number of Gram-positive infectious agents in SBP patients.

Community-acquired urinary tract infections: Causative agents and their resistance to antimicrobial drugs.

Background/Aim: Urinary tract infections (UTIs) are among the most common infections in outpatients. The aim of this study was to define the causative agents of urinary tract infections and their resistance to antimicrobial drugs in the urban area of central Serbia, as well as to evaluate eventual differences associated with age and gender of the patients. Methods: This retrospective study analysed data taken from routine, consecutively collected urine cultures of outpatients with symptomatic UTIs, collected from the Department of Microbiology, Institute of Public Health in Kragujevac, Serbia, from January 2009 to December 2013. Results: There were 71,905 urine cultures, and 24,713 (34.37%) of them were positive for bacterial pathogens. The most common pathogen was Escherichia coli (E. coli) (56.56%), followed by Klebsiella spp. (16.20%), Proteus spp. (14.68%), Enterococcus spp. (5.29%) and Pseudomonas aeruginosa (3.74%). E. coli and Enterococcus spp. isolation rates were lower in males ≥ 60 years old (23.71% and 4.87%, respectively), while Klebsiella spp. was more prevalent in this group (32.06%). The most common causative agents isolated from 15­29 years old male patients were Enterococcus spp. and Pseudomonas aeruginosa (13.28% each). Among women, the isolation rate of E.coli was high in all age groups (around 70%). Proteus spp. was frequently isolated from females ≤ 14 years old (13.27%), while Klebsiella spp. was the most frequent in the oldest age female group (10.99%). Conclusion: Choice of antibiotics for treatment of UTIs should be governed not only by the local resistance patterns, but also by gender and age of patients.