The association between vitamin D deficiency and community-acquired pneumonia: A meta-analysis of observational studies.

Emerging evidence has shown that vitamin D deficiency may be related with community-acquired pneumonia (CAP), but individually published studies showed inconclusive results. The aim of this study was to quantitatively summarize the association between vitamin D and the CAP.We conducted this meta-analysis though a systematic literature search of PubMed, Medline, and EMBASE up to 31 September 2018 with the following keywords 'vitamin D' or 'cholecalciferol' or '25-hydroxyvitamin D' or '25(OH)D' in combination with 'community-acquired pneumonia' or 'CAP' or 'pneumonia' with no limitations. This meta-analysis was performed following the guidelines of Meta-analysis of Observational Studies in Epidemiology. The association between vitamin D levels and CAP were measured as odds ratio (OR) and weighted mean difference (WMD). Results were combined using a random-effect or a fix-effect meta-analysis, and sensitivity analyses were conducted to explore potential factors.Eight observational studies involving 20,966 subjects were included. In this meta-analysis, CAP patients with vitamin D deficiency (serum 25(OH)D levels <20 ng/mL) experienced a significantly increased risk of CAP (odds ratio (OR) = 1.64, 95% confidence intervals (CI): 1.00, 2.67), and an obvious decrease of -5.63 ng/mL (95% CI: -9.11, -2.14) in serum vitamin D was demonstrated in CAP patients. Sensitivity analysis showed that exclusion of any single study did not materially alter the overall combined effect.The evidence from this meta-analysis indicates an association between vitamin D deficiency and an increased risk of CAP patients. However, well-designed trails are required to determine the explicit effect of vitamin D supplementation.

Association between serum 25-hydroxyvitamin D concentration and pulmonary infection in children.

We assessed the relationship between serum 25-hydroxyvitamin D (25(OH)D) level and community-acquired pneumonia (CAP) among Chinese children.This observational study examined children aged 3 days to 14 years (n = 1582) from the Capital Institute of Pediatrics in 2009 to 2011. There were 797 children in the CAP group and 785 controls. The CAP group was divided into 2 groups: a pneumonia group and pneumonia-induced sepsis group. The serum 25(OH)D level was estimated using micro whole blood chemiluminescence.The average serum 25(OH)D level in all samples was 25.32 ±â€Š14.07 ng/mL, with the CAP group showing a lower value than the control group (P < .001). There were also significant differences between the pneumonia group and pneumonia-induced sepsis group (P < .001). In the pneumonia-induced sepsis group, significant differences in serum 25(OH)D levels were observed in children who received mechanical ventilation or presenting with multiple organ dysfunction (P < .01).All serum 25(OH)D levels in the pneumonia group and pneumonia-induced sepsis group were below normal levels, particularly in the sepsis group. A lower serum 25(OH)D level was associated with more serious symptoms in CAP children. Children with low serum 25(OH)D levels may be at higher risk of receiving mechanical ventilation and presenting with multiple organ dysfunction. These findings suggest that vitamin D supplements are beneficial for the treatment and prevention of CAP.

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.

Etiologies of community-onset urinary tract infections requiring hospitalization and antimicrobial susceptibilities of causative microorganisms.

BACKGROUND: Community-onset urinary tract infections (CoUTIs) are the most common bacterial infections, and a decline in antibiotic susceptibility causes many clinical challenges. Adequate empiric antibiotic treatment can decrease unnecessary hospital stays and complications, while reducing the antimicrobial resistance progression. METHODS: From October 2014 to April 2015, we retrospectively enrolled patients who were at least 18 years old and required hospitalization for CoUTIs. Demographic variables of these patients, and uropathogens and their antimicrobial susceptibilities were evaluated. RESULTS: In total, 457 patients were enrolled in this study. Their mean age was 71.9 years, and 35.2% of the patients were male. Escherichia coli (54.5%) was the most common uropathogen, followed by Klebsiella pneumoniae (13.1%), Enterococcus spp. (7.1%), Pseudomonas aeruginosa (4.6%), and Proteus mirabilis (3.5%). Bacteremia was present in 25.2% of patients. Diabetes mellitus and acute kidney injury at admission were risk factors for CoUTIs with concomitant bacteremia. Among the UTI-associated bloodstream strains, E. coli (53.1%) was also the most predominant pathogen, followed by K. pneumoniae (11.3%), Staphylococcus aureus (6.1%), and P. mirabilis (4.3%). The overall susceptibility of cefazolin was 62.8%, ceftriaxone 71.4%, ceftazidime 82.8%, flomoxef 82%, cefepime 94.5%, ampicillin-sulbactam 41.6%, piperacillin-tazobactam 85%, levofloxacin 65.2%, trimethoprim-sulfamethoxazole 61.5%, imipenem 92.3%, gentamicin 76.1%, and amikacin 97.5%. Cefazolin-susceptible isolates could be found more frequently among patients who are less than 65 years of age and without diabetes mellitus, had no UTI episode in the past year, and have no bacteremia risk. Patients with nasogastric tube retention more commonly experienced antimicrobial resistance to all the third-generation cephalosporins. CONCLUSION: Third-generation cephalosporins effectively treated CoUTIs. However, patients with nasogastric tube retention more commonly experienced cephalosporin resistance. Cefepime, imipenem, and amikacin may be used in patients with higher antimicrobial resistance. In selected patients, cefazolin may still be an adequate drug of choice for CoUTIs.

Pneumococcal urinary antigen test: diagnostic yield and impact on antibiotic treatment.

BACKGROUND: The pneumococcal urinary antigen test (PUAT) is commonly used for the etiological diagnosis of community-acquired pneumonia (CAP) and can be useful for targeting pathogen-directed therapy. OBJECTIVES: The aim of our study was to evaluate the diagnostic yield of the PUAT and the impact of a positive PUAT result on antibiotic treatment in patients with CAP in a clinical non-research setting. METHODS: Adults hospitalized with CAP between January 2005 and November 2007 were studied retrospectively. All patients were tested by PUAT. The sensitivity of the PUAT was determined and changes in antibiotic therapy were assessed. RESULTS: A total of 681 patients with CAP were included. The microorganism most frequently identified was Streptococcus pneumoniae. It was found in 95 (14.0%) patients, and the PUAT increased the diagnostic yield to a total of 184 (27.0%) patients. The S. pneumoniae antigen was detected in 37 of 55 patients with definitive pneumococcal pneumonia (67.3%). Pneumococcal urinary antigen was positive in 56 of 95 pneumococcal cases (definite and probable), resulting in an overall test sensitivity of 59.0%. Positive results of the PUAT led physicians to narrow the spectrum of antibiotic treatment in 69 (45.1%) patients. CONCLUSIONS: The PUAT is a useful method for early detection of S. pneumoniae in patients with CAP, but the test was less sensitive in this clinical setting than prospective studies indicated. The PUAT results led physicians to narrow the spectrum of antibiotic treatment in approximately half of the relevant cases, which limited the impact of a positive PUAT.

Community acquired bacterial pneumonia: aetiology, laboratory detection and antibiotic susceptibility pattern.

This cross sectional study was conducted to identify the common bacterial causes of community acquired pneumonia (CAP) from sputum and blood by culture and polymerase chain reaction (PCR) and to evaluate the effectiveness of these tests. A total of 105 sputum and blood samples were collected from patients with pneumonia on clinical suspicion. Common causative bacterial agents of pneumonia were detected by Gram staining, cultures, biochemical tests and PCR. Among 55 sputum culture positive cases, a majority (61.82%) of the patients were in the age group between 21-50 years and the ratio between male and female was 2.5:1. Most (61.90%) of the cases were from the lower socio-economic group. Out of 105 samples, 23 (37.12%) were positive by Gram stain, 29 (27.62%) yielded growth in culture media and 37 (35.24%) were positive by PCR for Streptococcus pneumoniae and Haemophilus influenzae. Streptococcus pneumoniae was the most common aetiological agent (19.05%) followed by Klebsiella pneumoniae (13.33%), Haemophilus influenzae (8.57%) and Pseudomonas aeruginosa (5.71%). Multiplex PCR is a useful technique for rapid diagnosis of bacterial causes of pneumonia directly from sputum and blood. Considering culture as a gold standard, the sensitivity of PCR was 96.55% and specificity was 88.15%. More than 80% of Streptococcus pneumoniae isolates were found to be sensitive to ampicillin, amoxycillinclavulanate, and ceftriaxone. Susceptibilities to other antimicrobials ranged from 65% for azithromycin to 70% for levofloxacin. On the other hand, the Gram negative organisms were more sensitive to meropenem, ceftriaxone, amoxycillin-clavulanate and amikacin.

Angiotensin-converting enzyme inhibitor use and pneumonia risk in community-dwelling older adults: results from a population-based case-control study.

PURPOSE: To test whether angiotensin-converting enzyme (ACE) inhibitor use is associated with decreased risk of community-acquired pneumonia in older adults. METHODS: We analyzed data from a nested case-control study of community-dwelling, immunocompetent adults aged 65-94 within an integrated healthcare delivery system. Cases of ambulatory and hospitalized pneumonia from 2000 to 2003 were identified from International Classification of Disease, version 9, codes and validated using medical record review. Controls were matched to cases by age, sex, and calendar year. Using health plan pharmacy data, we defined current use as filling ≥2 prescriptions during the 180 days prior to the case's diagnosis date. We calculated standardized doses per day using World Health Organization defined daily doses. Multivariable conditional logistic regression estimated adjusted odds ratios (ORs) for pneumonia in relation to ACE inhibitor use, adjusting for comorbidity, functional and cognitive status, and other covariates from medical record review and pharmacy data. RESULTS: Current use of ACE inhibitors was seen in 23% (242/1039) of cases and 21% (433/2022) of controls. Lisinopril accounted for 95% of prescriptions. The OR for pneumonia comparing current use to no current use was 0.99 (95% confidence interval [CI] 0.83-1.19). The OR for use of more than two standardized daily doses per day was 1.39 (95% CI 0.93-2.06) compared to no current use. CONCLUSIONS: ACE inhibitor use is not associated with reduced pneumonia risk in community-dwelling older adults.

Elderly patients with community-acquired pneumonia: optimal treatment strategies.

Community-acquired pneumonia (CAP) is a common infectious disease that still causes substantial morbidity and mortality. Elderly people are frequently affected, and several issues related to care of this condition in the elderly have to be considered. This article reviews current recommendations of guidelines with a special focus on aspects of the care of elderly patients with CAP. The most common pathogen in CAP is still Streptococcus pneumoniae, followed by other pathogens such as Haemophilus influenzae, Mycoplasma pneumoniae, Chlamydophila pneumoniae and Legionella species. Antimicrobial resistance is an increasing problem, especially with regard to macrolide-resistant S. pneumoniae and fluoroquinolone-resistant strains. With regard to ß-lactam antibacterials, resistance by H. influenzae and Moraxella catarrhalis is important, as is the emergence of multidrug-resistant Staphylococcus aureus. The main management decisions should be guided by the severity of disease, which can be assessed by validated clinical risk scores such as CURB-65, a tool for measuring the severity of pneumonia based on assessment of confusion, serum urea, respiratory rate and blood pressure in patients aged ≥65 years. For the treatment of low-risk pneumonia, an aminopenicillin such as amoxicillin with or without a ß-lactamase inhibitor is frequently recommended. Monotherapy with macrolides is also possible, although macrolide resistance is of concern. When predisposing factors for special pathogens are present, a ß-lactam antibacterial combined with a ß-lactamase inhibitor, or the combination of a ß-lactam antibacterial, a ß-lactamase inhibitor and a macrolide, may be warranted. If possible, patients who have undergone previous antibacterial therapy should receive drug classes not previously used. For hospitalized patients with non-severe pneumonia, a common recommendation is empirical antibacterial therapy with an aminopenicillin in combination with a ß-lactamase inhibitor, or with fluoroquinolone monotherapy. With proven Legionella pneumonia, a combination of ß-lactams with a fluoroquinolone or a macrolide is beneficial. In severe pneumonia, ureidopenicillins with ß-lactamase inhibitors, broad-spectrum cephalosporins, macrolides and fluoroquinolones are used. A combination of a broad-spectrum ß-lactam antibacterial (e.g. cefotaxime or ceftriaxone), piperacillin/tazobactam and a macrolide is mostly recommended. In patients with a predisposition for Pseudomonas aeruginosa, a combination of piperacillin/tazobactam, cefepime, imipenem or meropenem and levofloxacin or ciprofloxacin is frequently used. Treatment duration of more than 7 days is not generally recommended, except for proven infections with P. aeruginosa, for which 15 days of treatment appears to be appropriate. Further care issues in all hospitalized patients are timely administration of antibacterials, oxygen supply in case of hypoxaemia, and fluid management and dose adjustments according to kidney function. The management of elderly patients with CAP is a challenge. Shifts in antimicrobial resistance and the availability of new antibacterials will change future clinical practice. Studies investigating new methods to detect pathogens, determine the optimal antimicrobial regimen and clarify the duration of treatment may assist in further optimizing the management of elderly patients with CAP.

[Community-acquired Staphylococcus aureus pneumonia following influenza and the choice of empirical antibiotic treatment]. / Thuis opgelopen pneumonie door Staphylococcus aureus na influenza en de keuze voor empirische antibiotische behandeling.

A 30-year-old man presented with community-acquired pneumonia (CAP), directly following influenza. Sputum Gram stain confirmed Staphylococcus aureus pneumonia. Initial empirical antimicrobial therapy did not cover S. aureus. The isolated S. aureus strain contained genes encoding exotoxins, such as Panton-Valentine leukocidin (PVL). This exotoxin is associated with high mortality and methicillin resistance, but in this patient the strain was susceptible to methicillin. The patient died. In the Netherlands the risk of methicillin resistance in PVL-positive S. aureus CAP is low but real. This should be taken into account when selecting empirical treatment, which can include the combination of flucloxacillin and rifampicin. This case report illustrates the difficulty in predicting the causative agent in CAP and highlights the usefulness of the sputum Gram stain. Moreover, clinical awareness and recognition of S. aureus CAP remains essential to the early initiation of directed therapy.