The Burden and Etiology of Community-Onset Pneumonia in the Aging Japanese Population: A Multicenter Prospective Study

Background

The increasing burden of pneumonia in adults is an emerging health issue in the era of global population aging. This study was conducted to elucidate the burden of community-onset pneumonia (COP) and its etiologic fractions in Japan, the world’s most aged society.

Methods

A multicenter prospective surveillance for COP was conducted from September 2011 to January 2013 in Japan. All pneumonia patients aged ≥15 years, including those with community-acquired pneumonia (CAP) and health care-associated pneumonia (HCAP), were enrolled at four community hospitals on four major islands. The COP burden was estimated based on the surveillance data and national statistics.

Results

A total of 1,772 COP episodes out of 932,080 hospital visits were enrolled during the surveillance. The estimated overall incidence rates of adult COP, hospitalization, and in-hospital death were 16.9 (95% confidence interval, 13.6 to 20.9), 5.3 (4.5 to 6.2), and 0.7 (0.6 to 0.8) per 1,000 person-years (PY), respectively. The incidence rates sharply increased with age; the incidence in people aged ≥85 years was 10-fold higher than that in people aged 15-64 years. The estimated annual number of adult COP cases in the entire Japanese population was 1,880,000, and 69.4% were aged ≥65 years. Aspiration-associated pneumonia (630,000) was the leading etiologic category, followed by Streptococcus pneumoniae-associated pneumonia (530,000), Haemophilus influenzae-associated pneumonia (420,000), and respiratory virus-associated pneumonia (420,000), including influenza-associated pneumonia (30,000).

Conclusions

A substantial portion of the COP burden occurs among elderly members of the Japanese adult population. In addition to the introduction of effective vaccines for S. pneumoniae and influenza, multidimensional approaches are needed to reduce the pneumonia burden in an aging society.     

Emergence of Streptococcus pyogenes emm102 Causing Toxic Shock Syndrome in Southern Taiwan during 2005–2012

Background

Streptococcal toxic shock syndrome (STSS) is an uncommon but life-threatening disease caused by Streptococcus pyogenes.

Methods

To understand the clinical and molecular characteristics of STSS, we analyzed clinical data and explored the emm types, superantigen genes, and pulsed-field gel electrophoresis of causative S. pyogenes isolates obtained between 2005 and 2012.

Results

In total, 53 patients with STSS were included in this study. The median age of the patients was 57 years (range: 9–83 years), and 81.1% were male. The most prevalent underlying disease was diabetes mellitus (45.3%). Skin and soft-tissue infection accounted for 86.8% of STSS. The overall mortality rate was 32.1%. Underlying diseases had no statistical impact on mortality. A total of 19 different emm types were identified. The most prevalent emm type was emm102 (18.9%), followed by emm11 (17%), emm1 (11.3%), emm87 (9.4%), and emm89 (7.5%). There was no statistically significant association between emm type and a fatal outcome. Among the superantigen genes, speB was the most frequently detected one (92.5%), followed by smeZ (90.6%), speG (81.1%), speC (39.6%), and speF (39.6%). The majority of emm102 strains were found to have speB, speC, speG, and smeZ. The presence of speG was negatively associated with a fatal outcome (P = 0.045).

Conclusions

Our surveillance revealed the emergence of uncommon emm types, particularly emm102, causing STSS in southern Taiwan. Characterization of clinical, epidemiological, and molecular characteristics of STSS will improve our understanding of this life-threatening disease.     

Etiology and Factors Associated with Pneumonia in Children under 5 Years of Age in Mali: A Prospective Case-Control Study

Background

There are very limited data on children with pneumonia in Mali. The objective was to assess the etiology and factors associated with community-acquired pneumonia in hospitalized children <5 years of age in Mali.

Methods

A prospective hospital-based case-control study was implemented in the Pediatric department of Gabriel Touré University Hospital at Bamako, Mali, between July 2011-December 2012. Cases were children with radiologically-confirmed pneumonia; Controls were hospitalized children without respiratory features, matched for age and period. Respiratory specimens, were collected to identify 19 viruses and 5 bacteria. Whole blood was collected from cases only. Factors associated with pneumonia were assessed by multivariate logistic regression.

Results

Overall, 118 cases and 98 controls were analyzed; 44.1% were female, median age was 11 months. Among pneumonia cases, 30.5% were hypoxemic at admission, mortality was 4.2%. Pneumonia cases differed from the controls regarding clinical signs and symptoms but not in terms of past medical history. Multivariate analysis of nasal swab findings disclosed that S. pneumoniae (adjusted odds ratio [aOR] = 3.4, 95% confidence interval [95% CI]: 1.6–7.0), human metapneumovirus (aOR = 17.2, 95% CI: 2.0–151.4), respiratory syncytial virus [RSV] (aOR = 7.4, 95% CI: 2.3–23.3), and influenza A virus (aOR = 10.7, 95% CI: 1.0–112.2) were associated with pneumonia, independently of patient age, gender, period, and other pathogens. Distribution of S. pneumoniae and RSV differed by season with higher rates of S. pneumoniae in January-June and of RSV in July-September. Pneumococcal serotypes 1 and 5 were more frequent in pneumonia cases than in the controls (P = 0.009, and P = 0.04, respectively).

Conclusions

In this non-PCV population from Mali, pneumonia in children was mainly attributed to S. pneumoniae, RSV, human metapneumovirus, and influenza A virus. Increased pneumococcal conjugate vaccine coverage in children could significantly reduce the burden of pneumonia in sub-Saharan African countries.     

High Prevalence of Methicillin-Resistant Staphylococcus aureus among Patients with Septic Arthritis Caused by Staphylococcus aureus

Background

This study investigated the clinical characteristics of patients with septic arthritis caused by Staphylococcus aureus and tried to identify the risk factors for methicillin-resistant S. aureus (MRSA) arthritis.

Methods

Between January 2008 and December 2011, patients with septic arthritis caused by S. aureus were identified from the computerized databases of a regional hospital and a medical center in southern Taiwan. The medical records of these patients were retrospectively reviewed.

Results

A total of 93 patients with S. aureus arthritis were identified, and MRSA arthritis was found in 38 (40.9%) cases. The mean age of the patients was 58 years, and 86 (92.5%) episodes were classified as community-acquired infections. Diabetes mellitus (n = 41, 44.1%) was the most common underlying disease, followed by chronic kidney disease and liver cirrhosis. Patients with MRSA arthritis were more frequently elderly and found in the setting of healthcare-associated infection than patients with methicillin-susceptible S. aureus (MSSA) infections. No other significant differences in clinical manifestations and outcomes were noted between these two groups of patients. Overall, the in-hospital mortality rate was 5.4%, and diabetes mellitus was the only risk factor for mortality.

Conclusions

MRSA is emerging in the setting of community-acquired septic arthritis. MRSA septic arthritis is more likely to develop in the elderly and in healthcare-associated infections than MSSA septic arthritis.     

The Importance of Bacterial and Viral Infections Associated with Adult Asthma Exacerbations in Clinical Practice

Background

Viral infection is one of the risk factors for asthma exacerbation. However, which pathogens are related to asthma exacerbation in adults remains unclear.

Objective

The relation between various infections and adult asthma exacerbations was investigated in clinical practice.

Methods

The study subjects included 50 adult inpatients due to asthma exacerbations and 20 stable outpatients for comparison. The pathogens from a nasopharyngeal swab were measured by multiplex PCR analysis.

Results

Asthma exacerbations occurred after a common cold in 48 inpatients. The numbers of patients with viral, bacterial, or both infections were 16, 9, and 9, respectively. The dominant viruses were rhinoviruses, respiratory syncytial virus, influenza virus, and metapneumovirus. The major bacteria were S. pneumoniae and H. influenzae. Compared to pathogen-free patients, the patients with pathogens were older and non-atopic and had later onset of disease, lower FeNO levels, lower IgE titers, and a higher incidence of comorbid sinusitis, COPD, or pneumonia. Compared to stable outpatients, asthma exacerbation inpatients had a higher incidence of smoking and comorbid sinusitis, COPD, or pneumonia. Viruses were detected in 50% of stable outpatients, but a higher incidence of rhinovirus, respiratory syncytial virus, and metapneumovirus infections was observed in asthma exacerbation inpatients. H. influenzae was observed in stable asthmatic patients. Other bacteria, especially S. pneumoniae, were important in asthma exacerbation inpatients.

Conclusion

Viral or bacterial infections were observed in 70% of inpatients with an asthma exacerbation in clinical practice. Infection with S. pneumoniae was related to adult asthma exacerbation.     

Value of Lung Ultrasonography in the Diagnosis and Outcome Prediction of Pediatric Community-Acquired Pneumonia with Necrotizing Change

Background

Lung ultrasonography has been advocated in diagnosing pediatric community-acquired pneumonia. However, its function in identifying necrotizing pneumonia, a complication, has not been explored. This study investigated the value of lung ultrasonography in diagnosing pediatric necrotizing pneumonia and its role in predicting clinical outcomes.

Methods

We retrospectively reviewed 236 children with community-acquired pneumonia who were evaluated using lung ultrasonography within 2–3 days after admission. The ultrasonographic features assessed included lung perfusion, the presence of hypoechoic lesions, and the amount of pleural effusion. Chest computed tomography was also performed in 96 patients as clinically indicated. Detailed records of clinical information were obtained.

Results

Our results showed a high correlation between the degree of impaired perfusion in ultrasonography and the severity of necrosis in computed tomography (r = 0.704). The degree of impaired perfusion can favorably be used to predict massive necrosis in computed tomography (area under the receiver operating characteristic curve, 0.908). The characteristics of impaired perfusion and hypoechoic lesions in ultrasonography were associated with an increased risk of pneumatocele formation (odds ratio (OR), 10.11; 95% CI, 2.95–34.64) and the subsequent requirement for surgical lung resection (OR, 8.28; 95% CI, 1.86–36.93). Furthermore, a longer hospital stay would be expected if moderate-to-massive pleural effusion was observed in addition to impaired perfusion in ultrasonography (OR, 3.08; 95% CI, 1.15–8.29).

Conclusion

Lung ultrasonography is favorably correlated with chest computed tomography in the diagnosis of necrotizing pneumonia, especially regarding massive necrosis of the lung. Because it is a simple and reliable imaging tool that is valuable in predicting clinical outcomes, we suggest that ultrasonography be applied as a surrogate for computed tomography for the early detection of severe necrotizing pneumonia in children.     

Clinical Outcomes and Microbiological Characteristics of Severe Pneumonia in Cancer Patients: A Prospective Cohort Study

Introduction

Pneumonia is the most frequent type of infection in cancer patients and a frequent cause of ICU admission. The primary aims of this study were to describe the clinical and microbiological characteristics and outcomes in critically ill cancer patients with severe pneumonia.

Methods

Prospective cohort study in 325 adult cancer patients admitted to three ICUs with severe pneumonia not acquired in the hospital setting. Demographic, clinical and microbiological data were collected.

Results

There were 229 (71%) patients with solid tumors and 96 (29%) patients with hematological malignancies. 75% of all patients were in septic shock and 81% needed invasive mechanical ventilation. ICU and hospital mortality rates were 45.8% and 64.9%. Microbiological confirmation was present in 169 (52%) with a predominance of Gram negative bacteria [99 (58.6%)]. The most frequent pathogens were methicillin-sensitive S. aureus [42 (24.9%)], P. aeruginosa [41(24.3%)] and S. pneumonia [21 (12.4%)]. A relatively low incidence of MR [23 (13.6%)] was observed. Adequate antibiotics were prescribed for most patients [136 (80.5%)]. In multivariate analysis, septic shock at ICU admission [OR 5.52 (1.92–15.84)], the use of invasive MV [OR 12.74 (3.60–45.07)] and poor Performance Status [OR 3.00 (1.07–8.42)] were associated with increased hospital mortality.

Conclusions

Severe pneumonia is associated with high mortality rates in cancer patients. A relatively low rate of MR pathogens is observed and severity of illness and organ dysfunction seems to be the best predictors of outcome in this population.     

Predictors of Severe Sepsis among Patients Hospitalized for Community-Acquired Pneumonia

Background

Severe sepsis, may be present on hospital arrival in approximately one-third of patients with community-acquired pneumonia (CAP).

Objective

To determine the host characteristics and micro-organisms associated with severe sepsis in patients hospitalized with CAP.

Results

We performed a prospective multicenter cohort study in 13 Spanish hospital, on 4070 hospitalized CAP patients, 1529 of whom (37.6%) presented with severe sepsis. Severe sepsis CAP was independently associated with older age (>65 years), alcohol abuse (OR, 1.31; 95% CI, 1.07–1.61), chronic obstructive pulmonary disease (COPD) (OR, 1.75; 95% CI, 1.50–2.04) and renal disease (OR, 1.57; 95% CI, 1.21–2.03), whereas prior antibiotic treatment was a protective factor (OR, 0.62; 95% CI, 0.52–0.73). Bacteremia (OR, 1.37; 95% CI, 1.05–1.79), S pneumoniae (OR, 1.59; 95% CI, 1.31–1.95) and mixed microbial etiology (OR, 1.65; 95% CI, 1.10–2.49) were associated with severe sepsis CAP.

Conclusions

CAP patients with COPD, renal disease and alcohol abuse, as well as those with CAP due to S pneumonia or mixed micro-organisms are more likely to present to the hospital with severe sepsis.     

Inference of Antibiotic Resistance and Virulence among Diverse Group A Streptococcus Strains Using emm Sequencing and Multilocus Genotyping Methods

Background

Group A Streptococcus pyogenes (GAS) exhibits a high degree of clinically relevant phenotypic diversity. Strains vary widely in terms of antibiotic resistance (AbR), clinical severity, and transmission rate. Currently, strain identification is achieved by emm typing (direct sequencing of the genomic segment coding for the antigenic portion of the M protein) or by multilocus genotyping methods. Phenotype analysis, including critical AbR typing, is generally achieved by much slower and more laborious direct culture-based methods.

Methodology/Principal Findings

We compare genotype identification (by emm typing and PCR/ESI-MS) with directly measured phenotypes (AbR and outbreak associations) for 802 clinical isolates of GAS collected from symptomatic patients over a period of 6 years at 10 military facilities in the United States. All independent strain characterization methods are highly correlated. This shows that recombination, horizontal transfer, and other forms of reassortment are rare in GAS insofar as housekeeping genes, primary virulence and antibiotic resistance determinants, and the emm gene are concerned. Therefore, genotyping methods offer an efficient way to predict emm type and the associated AbR and virulence phenotypes.

Conclusions/Significance

The data presented here, combined with much historical data, suggest that emm typing assays and faster molecular methods that infer emm type from genomic signatures could be used to efficiently infer critical phenotypic characteristics based on robust genotype: phenotype correlations. This, in turn, would enable faster and better-targeted responses during identified outbreaks of constitutively resistant or particularly virulent emm types.     

No Outbreak of Vancomycin and Linezolid Resistance in Staphylococcal Pneumonia over a 10-Year Period

Background

Staphylococci can cause wound infections and community- and nosocomial-acquired pneumonia, among a range of illnesses. Staphylococcus aureus and methicillin-resistant S. aureus (MRSA) have been rapidly increasing as a cause of infections worldwide in recent decades. Numerous reports indicate that S. aureus and MRSA are becoming resistant to many antibiotics, which makes them very dangerous. Therefore, this study retrospectively investigated the resistance to antimicrobial agents in all hospitalized patients suffering from community- or nosocomial-acquired pneumonia due to S. aureus and MRSA.

Methods

Information from the study groups suffering from either community- or nosocomial-acquired pneumonia caused by S. aureus or MRSA was gathered by searching records from 2004 to 2014 at the HELIOS Clinic Wuppertal, Witten/Herdecke University, Germany. The findings of antibiotic resistance were analyzed after the evaluation of susceptibility testing for S. aureus and MRSA.

Results

Total of 147 patients (63.9%, 95% CI 57.5%–69.8%), mean age 67.9 ± 18.5 years, with pneumonia triggered by S. aureus, and 83 patients (36.1%, 95% CI 30.2%–42.5%), mean age 72.3 ± 13.8 years, with pneumonia due to MRSA. S. aureus and MRSA developed no resistance to vancomycin (P = 0.019 vs. < 0.0001, respectively) or linezolid (P = 0.342 vs. < 0.0001, respectively). MRSA (95.3%) and S. aureus (56.3%) showed a high resistance to penicillin. MRSA (87.7%) was also found to have a high antibiotic resistance against ß-lactam antibiotics, compared to S. aureus (9.6%). Furthermore, MRSA compared to S. aureus, respectively, had increased antibiotic resistance to ciprofloxacin (90.1% vs. 17.0%), cefazolin (89.7% vs. 10.2%), cefuroxime (89.0% vs. 9.1%), levofloxacin (88.2% vs. 18.4%), clindamycin (78.0% vs. 14.7%), and erythromycin (76.5% vs. 20.8%).

Conclusion

No development of resistance was found to vancomycin and linezolid in patients with pneumonia caused by S. aureus and MRSA.     

Early Diagnosis of Pneumonia in Severe Stroke: Clinical Features and the Diagnostic Role of C-Reactive Protein

Background

Accurate diagnosis of pneumonia complicating severe stroke is challenging due to difficulties in physical examination, altered immune responses and delayed manifestations of radiological changes. The aims of this study were to describe early clinical features and to examine C-reactive protein (CRP) as a diagnostic marker of post-stroke pneumonia.

Methods

Patients who required nasogastric feeding and had no evidence of pneumonia within 7 days of stroke onset were included in the study and followed-up for 21 days with a daily clinical examination. Pneumonia was diagnosed using modified British Thoracic Society criteria.

Results

60 patients were recruited (mean age 77 years, mean National Institutes of Health Stroke Scale Score 19.47). Forty-four episodes of pneumonia were identified. Common manifestations on the day of the diagnosis were new onset crackles (43/44, 98%), tachypnoea>25/min (42/44, 95%), and oxygen saturation <90% (41/44, 93%). Cough, purulent sputum, and pyrexia >38°C were observed in 27 (61%), 25 (57%) and 15 (34%) episodes respectively. Leucocytosis (WBC>11,000/ml) and raised CRP (>10 mg/l) were observed in 38 (86%) and 43 (97%) cases of pneumonia respectively. The area under the ROC curve for CRP was 0.827 (95% CI 0.720, 0.933). The diagnostic cut-off for CRP with an acceptable sensitivity (>0.8) was 25.60 mg/L (Youden index (J) 0.515; sensitivity 0.848; specificity 0.667). A cut-off of 64.65 mg/L had the highest diagnostic accuracy (J 0.562; sensitivity 0.636; specificity 0.926).

Conclusion

Patients with severe stroke frequently do not manifest key diagnostic features of pneumonia such as pyrexia, cough and purulent sputum early in their illness. The most common signs in this group are new-onset crackles, tachypnoea and hypoxia. Our results suggest that a CRP >25 mg/L should prompt investigations for pneumonia while values >65 mg/L have the highest diagnostic accuracy to justify consideration of this threshold as a diagnostic marker of post-stroke pneumonia.     

Severe Community-Acquired Pneumonia Caused by Human Adenovirus in Immunocompetent Adults: A Multicenter Case Series

Background

Severe community-acquired pneumonia (CAP) caused by human adenovirus (HAdV), especially HAdV type 55 (HAdV-55) in immunocompetent adults has raised increasing concerns. Clinical knowledge of severe CAP and acute respiratory distress syndrome induced by HAdV-55 is still limited, though the pathogen has been fully characterized by whole-genome sequencing.

Methods

We conducted a multicentre retrospective review of all consecutive patients with severe CAP caused by HAdV in immunocompetent adults admitted to the Emergency Department Intensive Care Unit of two hospitals in Northern China between February 2012 and April 2014. Clinical, laboratory, radiological characteristics, treatments and outcomes of these patients were collected and analyzed.

Results

A total of 15 consecutive severe CAP patients with laboratory-confirmed adenovirus infections were included. The median age was 30 years and all cases were identified during the winter and spring seasons. HAdV-55 was the most frequently (11/15) detected HAdV type. Persistent high fever, cough and rapid progression of dyspnea were typically reported in these patients. Significantly increased pneumonia severity index (PSI), respiratory rate, and lower PaO₂/FiO₂, hypersensitive CRP were reported in non-survivors compared to survivors (P = 0.013, 0.022, 0.019 and 0.026, respectively). The rapid development of bilateral consolidations within 10 days after illness onset were the most common radiographic finding, usually accompanied by adjacent ground glass opacities and pleural effusions. Total mortality was 26.7% in this study. Corticosteroids were prescribed to 14 patients in this report, but the utilization rate between survivors and non-survivors was not significant.

Conclusions

HAdV and the HAdV-55 sub-type play an important role among viral pneumonia pathogens in hospitalized immunocompetent adults in Northern China. HAdV should be tested in severe CAP patients with negative bacterial cultures and a lack of response to antibiotic treatment, even if radiologic imaging and clinical presentation initially suggest bacterial pneumonia.     

Severe Human Influenza Infections in Thailand: Oseltamivir Treatment and Risk Factors for Fatal Outcome

Background

Influenza is often not recognized as an important cause of severe or fatal disease in tropical and subtropical countries in Southeast Asia. The extent to which Oseltamivir treatment may protect against a fatal outcome in severe influenza infections is not known. Thailand''s National Avian Influenza Surveillance (NAIS) system affords a unique opportunity to describe the epidemiology of laboratory-confirmed severe and fatal human influenza infections.

Methodology/Principal Findings

During January 2004 through December 2006, 11,641 notifications to the NAIS were investigated in 73 of 76 Thai provinces. Clinical and demographic data and respiratory swab specimens were collected and tested by PCR for influenza. Using the NAIS database, we identified all patients with laboratory confirmed human influenza (A/H3N2, A/H1N1 and Type B) infection. A retrospective medical record review was conducted on all fatal cases with laboratory confirmed influenza and from a sample of hospitalized cases in 28 provinces. The association of underlying risk factors, Oseltamivir treatment and risk of a fatal outcome were examined. Human influenza infections were identified in 2,075 (18%) cases. Twenty-two (1%) deaths occurred including seven deaths in children less than ten years of age. Thirty-five percent of hospitalized human influenza infections had chest X-ray confirmed pneumonia. Current or former smoking; advanced age, hypertension and underlying cardiovascular, pulmonary or endocrine disease were associated with a fatal outcome from human influenza infection. Treatment with Oseltamivir was statistically associated with survival with a crude OR of .11 (95% CI: 0.04–0.30) and .13 (95% CI: 0.04–0.40) after controlling for age.

Conclusions

Severe and fatal human influenza infections were commonly identified in the NAIS designed to identify avian A/H5N1 cases. Treatment with Oseltamivir is associated with survival in hospitalized human influenza pneumonia patients.     

Antibiotic Resistance of Pseudomonas aeruginosa in Pneumonia at a Single University Hospital Center in Germany over a 10-Year Period

Background

Pseudomonas aeruginosa is a common cause of community-acquired and nosocomial-acquired pneumonia. The development of resistance of P. aeruginosa to antibiotics is increasing globally due to the overuse of antibiotics. This article examines, retrospectively, the antibiotic resistance in patients with community-acquired versus nosocomial-acquired pneumonia caused by P. aeruginosa or multidrug-resistant (MDR) P. aeruginosa.

Methods

Data from patients with community-acquired and nosocomial-acquired pneumonia caused by P. aeruginosa and MDR P. aeruginosa were collected from the hospital charts at the HELIOS Clinic, Witten/Herdecke University, Wuppertal, Germany, between January 2004 and August 2014. An antibiogram was created from all study patients with community-acquired and nosocomial-acquired pneumonia caused by P. aeruginosa or MDR P. aeruginosa.

Results

A total of 168 patients with mean age 68.1 ± 12.8 (113 [67.3% males and 55 [32.7%] females) were identified; 91 (54.2%) had community-acquired and 77 (45.8%) had nosocomial-acquired pneumonia caused by P. aeruginosa. Patients with community-acquired versus nosocomial-acquired pneumonia had a mean age of 66.4 ± 13.8 vs. 70.1 ± 11.4 years [59 vs. 54 (64.8% vs. 70.1%) males and 32 vs. 23 (35.2% vs. 29.9%) females]. They included 41 (24.4%) patients with pneumonia due to MDR P. aeruginosa: 27 (65.9%) community-acquired and 14 (34.1%) nosocomial-acquired cases. P. aeruginosa and MDR P. aeruginosa showed a very high resistance to fosfomycin (community-acquired vs. nosocomial-acquired) (81.0% vs. 84.2%; 0 vs. 85.7%). A similar resistance pattern was seen with ciprofloxacin (35.2% vs. 24.0%; 70.4% vs. 61.5%), levofloxacin (34.6% vs. 24.5%; 66.7% vs. 64.3%), ceftazidime (15.9% vs. 30.9; 33.3% vs. 61.5%), piperacillin (24.2% vs. 29.9%; 44.4% vs. 57.1%), imipenem (28.6% vs. 27.3%; 55.6% vs. 50.0%), piperacillin and tazobactam (23.1% vs. 28.6%; 44.4% vs. 50.0%), tobramycin (28.0% vs. 17.2%; 52.0% vs. 27.3%), gentamicin (26.4% vs. 18.2%; 44.4% vs. 21.4%), and meropenem (20.2% vs. 20.3%; 42.3% vs. 50.0%). An elevated resistance of P. aeruginosa and MDR P. aeruginosa was found for cefepime (11.1% vs. 23.3%; 25.9% vs. 50.0%), and amikacin (10.2% vs. 9.1%; 27.3% vs. 9.1%). Neither pathogen was resistant to colistin (P = 0.574).

Conclusion

While P. aeruginosa and MDR P. aeruginosa were resistant to a variety of commonly used antibiotics, they were not resistant to colistin in the few isolates recovered from patients with pneumonia.     

Relationship between Expression of the Family of M Proteins and Lipoteichoic Acid to Hydrophobicity and Biofilm Formation in Streptococcus pyogenes

Background

Hydrophobicity is an important attribute of bacteria that contributes to adhesion and biofilm formation. Hydrophobicity of Streptococcus pyogenes is primarily due to lipoteichoic acid (LTA) on the streptococcal surface but the mechanism(s) whereby LTA is retained on the surface is poorly understood. In this study, we sought to determine whether members of the M protein family consisting of Emm (M protein), Mrp (M-related protein), Enn (an M-like protein), and the streptococcal protective antigen (Spa) are involved in anchoring LTA in a manner that contributes to hydrophobicity of the streptococci and its ability to form biofilms.

Methodology/Principal Findings

Isogenic mutants defective in expression of emm, mrp, enn, and/or spa genes of eight different serotypes and their parental strains were tested for differences in LTA bound to surface proteins, LTA released into the culture media, and membrane-bound LTA. The effect of these mutations on the ability of streptococci to form a hydrophobic surface and to generate biofilms was also investigated. A recombinant strain overexpressing Emm1 was also engineered and similarly tested. The serotypes tested ranged from those that express only a single M protein gene to those that express two or three members of the M protein family. Overexpression of Emm1 led to enhanced hydrophobicity and biofilm formation. Inactivation of emm in those serotypes expressing only a single emm gene reduced biofilm formation, and protein-bound LTA on the surface, but did not alter the levels of membrane-bound LTA. The results were more varied in those serotypes that express two to three members of the M protein family.

Conclusions/Significance

Our findings suggest that the formation of complexes with members of the M protein family is a common mechanism for anchoring LTA on the surface in a manner that contributes to hydrophobicity and to biofilm formation in S. pyogenes, but these activities in some serotypes are dependent on a trypsin-sensitive protein(s) that remains to be identified. The need for interactions between LTA and M proteins may impose functional constraints that limit variations in the sequence of the M proteins, major virulence factors of S. pyogenes.     

Clinical Presentation and Birth Outcomes Associated with Respiratory Syncytial Virus Infection in Pregnancy

Background

Respiratory syncytial virus (RSV) is the most important cause of viral pneumonia in children worldwide. A maternal vaccine may protect both the mother and infant from RSV illness. The epidemiology and clinical presentation of RSV in pregnant and postpartum women is not well-described.

Methods

Data were collected from a prospective, randomized trial of influenza immunization in pregnant women in rural southern Nepal. Women were enrolled in their second trimester of pregnancy and followed until six months postpartum. Active weekly home-based surveillance for febrile respiratory illness was performed. Mid-nasal swabs collected with episodes of respiratory illness were tested for RSV by real-time polymerase chain reaction.

Results

RSV was detected in 14 (0.4%) illness episodes in 3693 women over 3554 person-years of surveillance from 2011–2014. RSV incidence was 3.9/1000 person-years overall, and 11.8/1000 person-years between September and December. Seven (50%) women sought care for RSV illness; none died. Of the 7 (50%) illness episodes during pregnancy, all had live births with 2 (29%) preterm births and a median birthweight of 3060 grams. This compares to 469 (13%) preterm births and a median birthweight of 2790 grams in women without RSV during pregnancy. Of the 7 mothers with postpartum RSV infection, RSV was detected in 4 (57%) of their infants.

Conclusions

RSV was an uncommon cause of febrile respiratory illness in mothers during pregnancy in Nepal. These data will inform prevention and therapeutic strategies against RSV in resource-limited settings.     

A Genomic Approach to Resolving Relapse versus Reinfection among Four Cases of Buruli Ulcer

Background

Increased availability of Next Generation Sequencing (NGS) techniques allows, for the first time, to distinguish relapses from reinfections in patients with multiple Buruli ulcer (BU) episodes.

Methodology

We compared the number and location of single nucleotide polymorphisms (SNPs) identified by genomic screening between four pairs of Mycobacterium ulcerans isolates collected at the time of first diagnosis and at recurrence, derived from a collection of almost 5000 well characterized clinical samples from one BU treatment center in Benin.

Principal Findings

The findings suggest that after surgical treatment—without antibiotics—the second episodes were due to relapse rather than reinfection. Since specific antibiotics were introduced for the treatment of BU, the one patient with a culture available from both disease episodes had M. ulcerans isolates with a genomic distance of 20 SNPs, suggesting the patient was most likely reinfected rather than having a relapse.

Conclusions

To our knowledge, this study is the first to study recurrences in M. ulcerans using NGS, and to identify exogenous reinfection as causing a recurrence of BU. The occurrence of reinfection highlights the contribution of ongoing exposure to M. ulcerans to disease recurrence, and has implications for vaccine development.     

Is Zolpidem Associated with Increased Risk of Fractures in the Elderly with Sleep Disorders? A Nationwide Case Cross-Over Study in Taiwan

Background

We conducted a study using a case-crossover design to clarify the risk of acute effects of zolpidem and benzodiazepine on all-sites of fractures in the elderly.

Design of study

Case-crossover design.

Methods and Materials

Elderly enrollees (n = 6010) in Taiwan’s National Health Insurance Research Database with zolpidem or benzodiazepine use were analyzed for the risk of developing fractures.

Results

After adjusting for medications such as antipsychotics, antidepressants, and diuretics, or comorbidities such as hypertension, osteoarthritis, osteoporosis, rheumatoid arthritis and depression, neither zolpidem nor benzodiazepine was found to be associated with increased risk in all-sites fractures. Subjects without depression were found to have an increased risk of fractures. Diazepam is the only benzodiazepine with increased risk of fractures after adjusting for medications and comorbidities. Hip and spine were particular sites for increased fracture risk, but following adjustment for comorbidities, the associations were found to be insignificant.

Conclusion

Neither zolpidem nor benzodiazepine was associated with increased risk of all-site fractures in this case cross-over study after adjusting for medications or comorbidities in elderly individuals with insomnia. Clinicians should balance the benefits and risks for prescribing zolpidem or benzodiazepine in the elderly accordingly.