Aminopyridines Restore Ventilation and Reverse Respiratory Acidosis at Late Stages of Botulism in Mice.

Botulinum neurotoxin (BoNT) is a potent protein toxin that causes muscle paralysis and death by asphyxiation. Treatments for symptomatic botulism are intubation and supportive care until respiratory function recovers. Aminopyridines have recently emerged as potential treatments for botulism. The clinically approved drug 3,4-diaminopyridine (3,4-DAP) rapidly reverses toxic signs of botulism and has antidotal effects when continuously administered in rodent models of lethal botulism. Although the therapeutic effects of 3,4-DAP likely result from the reversal of diaphragm paralysis, the corresponding effects on respiratory physiology are not understood. Here, we combined unrestrained whole-body plethysmography (UWBP) with arterial blood gas measurements to study the effects of 3,4-DAP, and other aminopyridines, on ventilation and respiration at terminal stages of botulism in mice. Treatment with clinically relevant doses of 3,4-DAP restored ventilation in a dose-dependent manner, producing significant improvements in ventilatory parameters within 10 minutes. Concomitant with improved ventilation, 3,4-DAP treatment reversed botulism-induced respiratory acidosis, restoring blood levels of CO2, pH, and lactate to normal physiologic levels. Having established that 3,4-DAP-mediated improvements in ventilation were directly correlated with improved respiration, we used UWBP to quantitatively evaluate nine additional aminopyridines in BoNT/A-intoxicated mice. Multiple aminopyridines were identified with comparable or enhanced therapeutic efficacies compared with 3,4-DAP, including aminopyridines that selectively improved tidal volume versus respiratory rate and vice versa. In addition to contributing to a growing body of evidence supporting the use of aminopyridines to treat clinical botulism, these data lay the groundwork for the development of aminopyridine derivatives with improved pharmacological properties. SIGNIFICANCE STATEMENT: There is a critical need for fast-acting treatments to reverse respiratory paralysis in patients with botulism. This study used unrestrained, whole-body plethysmography and arterial blood gas analysis to show that aminopyridines rapidly restore ventilation and respiration and reverse respiratory acidosis when administered to mice at terminal stages of botulism. In addition to supporting the use of aminopyridines as first-line treatments for botulism symptoms, these data are expected to contribute to the development of new aminopyridine derivatives with improved pharmacological properties.

Gun violence in K-12 schools in the United States: Moving towards a preventive (versus reactive) framework.

Intentional shootings in K-12 schools in the U.S. persist as a public health problem. The number of shootings in K-12 schools has increased precipitously since 2017. And with approximately 100,000 K-12 public schools nationally serving 51 million children, investing in a comprehensive gun violence prevention strategy is critical. Unfortunately, our current school gun violence prevention approach almost exclusively centers reactive strategies that are in place to respond to acts of gun violence in the moment, rather than preventive strategies that would prevent them from occurring at all. Reliance on these strategies alone, however, is not sufficient. In line with the core tenets of public health prevention and the Whole School, Whole Child, Whole Community model, we present a more expansive school gun violence prevention framework that broadens the spectrum of what constitutes "school gun violence prevention." Our work highlights how enhancing basic neighborhood and school structures-including investments in public libraries, affordable housing, and universal school-based violence prevention programs-are key to both preventing gun violence and promoting well-being. We also highlight the role of stricter gun laws, reasonable school security efforts, bystander interventions, building awareness within school communities, and meaningful investments in early interventions and mental health services. Children, who have been tragically exposed to any number of adverse experiences in the wake of the COVID-19 pandemic, deserve more reasoned choices and large-scale investments in understanding and cutting off the root causes of school gun violence; not just a reliance on strategies that focus on what to do in the moment of a violent act. As gun violence in K-12 schools persists, we must reframe the discourse about school gun violence around prevention, not reaction.

Clinical Manifestations and Stool Load of Atypical Enteropathogenic Escherichia coli Infections in United States Children and Adults.

BACKGROUND & AIMS: There is debate whether atypical enteropathogenic Escherichia coli (aEPEC) causes disease in adults. aEPEC is commonly detected in symptomatic and asymptomatic individuals. aEPEC, in contrast to typical EPEC, lacks bundle-forming pili, altering its pathogenicity. Here, we define for the first time the clinical manifestations of sporadic aEPEC infection in United States children and adults and determine whether EPEC load correlates with disease. METHODS: This is a retrospective case-control study of 380 inpatients/outpatients of all ages. EPEC load in stools was determined by quantitative polymerase chain reaction. RESULTS: Diarrhea, vomiting, abdominal pain, and fever were more prevalent in EPEC-positive cases than in EPEC-negative controls. aEPEC infection caused mostly acute, mild diarrhea lasting for 6 to 13 days. However, some had severe diarrhea with 10 to 40 bowel movements per day or had persistent/chronic diarrhea. Fever, vomiting, and abnormal serum sodium levels were more common in children. Adults more often reported abdominal pain and longer duration of diarrhea. Symptomatic aEPEC infection was associated with leukocytosis in 24% of patients. EPEC load >0.1% was associated with symptomatic infection; however, loads varied greatly. Co-infecting pathogens did not alter diarrhea severity or EPEC load. Longitudinal data reveal that some are colonized for months to years or are repeatedly infected. CONCLUSIONS: aEPEC is associated with a wide array of symptoms in adults, ranging from asymptomatic carriage to severe diarrhea. Higher EPEC loads are associated with presence of symptoms, but bacterial load does not predict disease or severity. Future studies are needed to understand bacterial and host factors that contribute to aEPEC pathogenicity to improve diagnostic tools and clinical care.

Spatial prediction of soil depth using environmental covariates by quantile regression forest model.

Prediction of soil depth for larger areas provides primary information on soil depth and its spatial distribution that becomes vital for land resource management, crop, nutrient, and ecosystem modeling. The present study assessed the spatial distribution of soil depth over 160,205 km2 of Andhra Pradesh, India, using 20 covariables by quantile regression forest (QRF). An aggregate of 2854 soil datasets compiled from various physiographic units were randomly partitioned into 80:20 ratio for calibration (2283 samples) and validation (571 samples). Landsat imagery, terrain datasets (8), and bioclimatic factors (11) were utilized as covariates. The QRF model outputs signified that precipitation, multi-resolution index of valley bottom flatness (MrVBF), mean diurnal range, isothermality, and elevation were the most important variables influencing soil depth variability across the landscape. Spatial prediction of soil depth by QRF model yielded a ME of - 1.81 cm, RMSE of 34 cm, PICP of 90.2, and a R2 value of 42% as compared to ordinary kriging which results in a ME of - 0.14 cm, a RMSE of 37 cm, and a R2 value of 32%. As soil depth is spatially dynamic and has significant correlation with terrain and environmental covariates, better prediction was possible by the QRF model. However, high-density bioclimatic variables could be utilized along with high-resolution terrain variables to improve the predictive accuracy.

Increased Risk of Pancreatitis after Endoscopic Retrograde Cholangiopancreatography Following a Positive Intraoperative Cholangiogram: A Single-Center Experience.

BACKGROUND/AIMS: To determine if patients with a positive intraoperative cholangiogram (IOC) who undergo a subsequent endoscopic retrograde cholangiopancreatography (ERCP) have an increased risk of post-ERCP pancreatitis (PEP) compared to those who undergo ERCP directly for suspected common bile duct stones. METHODS: A retrospective case-control study was performed from 2010 to 2016. Cases included inpatients with a positive IOC at cholecystectomy who underwent subsequent ERCP. The control group included age-sex matched cohorts who underwent ERCP for choledocholithiasis. Multivariate logistic regression was used to assess the association between PEP and positive IOC, adjusting for matching variables and additional potential confounders. RESULTS: Of the 116 patients that met the inclusion criteria, there were 91 women (78%) in each group. Nine patients (7.8%) developed PEP in the IOC group, compared to 3 patients in the control group (2.6%). The use of pancreatic duct stents and rectal indomethacin was similar in both groups. After adjusting for age, sex, total bilirubin levels, and any stent placement, patients with a positive IOC had a significantly increased risk of PEP (odds ratio, 4.79; 95% confidence interval, 1.05-21.89; p<0.05). CONCLUSION: In this single-center case-control study, there was a five-fold increased risk of PEP following a positive IOC compared to an age-sex matched cohort.

Increased Risk of Pancreatitis after Endoscopic Retrograde Cholangiopancreatography Following a Positive Intraoperative Cholangiogram: A Single-Center Experience

Background/Aims@#To determine if patients with a positive intraoperative cholangiogram (IOC) who undergo a subsequent endoscopic retrograde cholangiopancreatography (ERCP) have an increased risk of post-ERCP pancreatitis (PEP) compared to those who undergo ERCP directly for suspected common bile duct stones. @*Methods@#A retrospective case-control study was performed from 2010 to 2016. Cases included inpatients with a positive IOC at cholecystectomy who underwent subsequent ERCP. The control group included age-sex matched cohorts who underwent ERCP for choledocholithiasis. Multivariate logistic regression was used to assess the association between PEP and positive IOC, adjusting for matching variables and additional potential confounders. @*Results@#Of the 116 patients that met the inclusion criteria, there were 91 women (78%) in each group. Nine patients (7.8%) developed PEP in the IOC group, compared to 3 patients in the control group (2.6%). The use of pancreatic duct stents and rectal indomethacin was similar in both groups. After adjusting for age, sex, total bilirubin levels, and any stent placement, patients with a positive IOC had a significantly increased risk of PEP (odds ratio, 4.79; 95% confidence interval, 1.05–21.89; p<0.05). @*Conclusions@#In this single-center case-control study, there was a five-fold increased risk of PEP following a positive IOC compared to an age-sex matched cohort.

The Utility of Endoscopic Ultrasound in Patients with Isolated Elevations in Serum Amylase and/or Lipase.

BACKGROUND/AIMS: The aim of this study was to describe the diagnostic yield of endoscopic ultrasound (EUS) in patients with isolated elevated levels of amylase and/or lipase. METHODS: A retrospective chart review was conducted at a large academic medical center from 2000 to 2016. Patients were selected based on having elevated amylase, lipase, or both, but without a diagnosis of pancreatitis or known pancreatobiliary disease. Patients were excluded if they had abnormal liver function tests or abnormal imaging of the pancreas. RESULTS: Of 299 EUS procedures performed, 38 met inclusion criteria. Symptoms were present in 31 patients, most frequently abdominal pain (87%). In 20 patients (53%), initial EUS most commonly found chronic pancreatitis (n=7; 18%), sludge (5; 13%), or new diagnosis of pancreas divisum (3; 8%). In the asymptomatic patients (7), 3 had a finding on EUS, most importantly sludge (2), stone (1), and pancreas divisum (1). No patients were diagnosed with a mass or pancreatic cyst. During the follow up period, 6 patients (22%) had cholecystectomy. CONCLUSION: In our study of patients with isolated elevations in amylase and/or lipase without acute pancreatitis who underwent EUS, approximately 50% had a pancreatobiliary finding, most commonly chronic pancreatitis or biliary sludge.

The Utility of Endoscopic Ultrasound in Patients with Isolated Elevations in Serum Amylase and/or Lipase

BACKGROUND/AIMS: The aim of this study was to describe the diagnostic yield of endoscopic ultrasound (EUS) in patients with isolated elevated levels of amylase and/or lipase. METHODS: A retrospective chart review was conducted at a large academic medical center from 2000 to 2016. Patients were selected based on having elevated amylase, lipase, or both, but without a diagnosis of pancreatitis or known pancreatobiliary disease. Patients were excluded if they had abnormal liver function tests or abnormal imaging of the pancreas. RESULTS: Of 299 EUS procedures performed, 38 met inclusion criteria. Symptoms were present in 31 patients, most frequently abdominal pain (87%). In 20 patients (53%), initial EUS most commonly found chronic pancreatitis (n=7; 18%), sludge (5; 13%), or new diagnosis of pancreas divisum (3; 8%). In the asymptomatic patients (7), 3 had a finding on EUS, most importantly sludge (2), stone (1), and pancreas divisum (1). No patients were diagnosed with a mass or pancreatic cyst. During the follow up period, 6 patients (22%) had cholecystectomy. CONCLUSIONS: In our study of patients with isolated elevations in amylase and/or lipase without acute pancreatitis who underwent EUS, approximately 50% had a pancreatobiliary finding, most commonly chronic pancreatitis or biliary sludge.

Enzymatic synthesis and chemical inversion provide both enantiomers of bioactive epoxydocosapentaenoic acids.

Epoxy PUFAs are endogenous cytochrome P450 (P450) metabolites of dietary PUFAs. Although these metabolites exert numerous biological effects, attempts to study their complex biology have been hampered by difficulty in obtaining the epoxides as pure regioisomers and enantiomers. To remedy this, we synthesized 19,20- and 16,17-epoxydocosapentaenoic acids (EDPs) (the two most abundant EDPs in vivo) by epoxidation of DHA with WT and the mutant (F87V) P450 enzyme BM3 from Bacillus megaterium WT epoxidation yielded a 4:1 mixture of 19,20:16,17-EDP exclusively as (S,R) enantiomers. Epoxidation with the mutant (F87V) yielded a 1.6:1 mixture of 19,20:16,17-EDP; the 19,20-EDP fraction was ∼9:1 (S,R):(R,S), but the 16,17-EDP was exclusively the (S,R) enantiomer. To access the (R,S) enantiomers of these EDPs, we used a short (four-step) chemical inversion sequence, which utilizes 2-(phenylthio)ethanol as the epoxide-opening nucleophile, followed by mesylation of the resulting alcohol, oxidation of the thioether moiety, and base-catalyzed elimination. This short synthesis cleanly converts the (S,R)-epoxide to the (R,S)-epoxide without loss of enantiopurity. This method, also applicable to eicosapentaenoic acid and arachidonic acid, provides a simple, cost-effective procedure for accessing larger amounts of these metabolites.

Extended-Spectrum Beta-lactamase Producers: Detection for the Diagnostic Laboratory.

BACKGROUND AND OBJECTIVES: Discovered in 1983, Extended spectrum beta-lactamase (ESBL) producers are still the leading cause of infections in India. Its prompt detection is crucial to the clinical management. The Clinical Laboratory Standards Institute (CLSI) recommends phenotypic screening and confirmatory tests to identify the ESBL producer making it cost and time consuming for the diagnostic laboratory. We compare here the screening and confirmatory tests offering a solution to the CLSI recommendation. METHODS: Nosocomial isolates E. coli (71) and K. pneumoniae (25) resistant to cefotaxime and ceftazidime were included. CLSI recommended testing with cefotaxime, ceftazidime and in combination with clavulanic acid by disk diffusion and agar dilution methods were performed. E-test was performed on discrepant results. To determine the genetic relatedness of the organisms, 22 Medical and Surgical ICU isolates were genotyped by PFGE. Dendrogram was constructed using dice co-efficient, UPGMA method with diversity database software. RESULTS AND CONCLUSIONS: Phenotypic screening disk diffusion test versus the confirmatory agar dilution MIC tests with cefotaxime and ceftazidime correlated well with the final ESBL status (kappa 0.852 and 0.905 P < 0.001) and (kappa 0.911 and 0.822 P < 0.001). The tests show 99-100% sensitivity, 75-83.3% specificity, and positive likelihood ratios between 4.0 -5.9. E-test confirmed 6 of 12 discordant results as ESBLs. Of the 96 nosocomial isolates screened as possible ESBL producers by the Kirby-Bauer disk diffusion test, 86.5% were confirmed ESBL producers. Genotyping on the ICU isolates by PFGE revealed a genetically diverse population suggesting no transmission of phenotypically similar ESBL strains within the ICUs.

Brainstem micro-abscesses caused by Burkholderia pseudomallei in a 10-month-old infant: a case report.

Melioidosis is an uncommon tropical infectious disease caused by Burkholderia pseudomallei. Neurological complications of melioidosis are extremely uncommon in infants. A 10-month-old girl is described who presented with disseminated melioidosis with subcutaneous nodules, arthritis, hepatomegaly and a lung cavity, and developed a left medial rectus palsy. Cranial MRI demonstrated mid-brain, pontine and basal ganglia micro-abscesses. Therapy with meropenem and cotrimoxazole led to resolution of the medial nerve palsy. At 5-month follow-up, the child had no residual neurological deficits.

Metabolism of Dopamine in Nucleus Accumbens Astrocytes Is Preserved in Aged Mice Exposed to MPTP.

Parkinson disease (PD) is prevalent in elderly individuals and is characterized by selective degeneration of nigrostriatal dopamine (NSDA) neurons. Interestingly, not all dopamine (DA) neurons are affected equally by PD and aging, particularly mesolimbic (ML) DA neurons. Here, effects of aging were examined on presynaptic DA synthesis, reuptake, metabolism and neurotoxicant susceptibility of NSDA and mesolimbic dopamine (MLDA) neurons and astrocyte DA metabolism. There were no differences in phenotypic markers of DA synthesis, reuptake or metabolism in NSDA or MLDA neurons in aged mice, but MLDA neurons displayed lower DA stores. Astrocyte metabolism of DA to 3-methoxytyramine (3-MT) in the striatum was decreased in aged mice, but was maintained in the nucleus accumbens. Despite diminished DA vesicular storage capacity in MLDA neurons, susceptibility to acute neurotoxicant exposure was similar in young and aged mice. These results reveal an age- and neurotoxicant-induced impairment of DA metabolic activity in astrocytes surrounding susceptible NSDA neurons as opposed to maintenance of DA metabolism in astrocytes surrounding resistant MLDA neurons, and suggest a possible therapeutic target for PD.

Prevalence and characteristics of Streptococcus pneumoniae "putative serotype 6E" isolates from Asian countries.

The prevalence, antimicrobial susceptibility, and genotypes of Streptococcus pneumoniae "putative serotype 6E" isolates from Asian countries were investigated. A total of 244 S. pneumoniae serogroup 6 isolates obtained from 11 Asian countries were included in this study. Of the 244 serogroup 6 isolates, 101 (41.4%) were typed as "putative serotype 6E," followed by serotypes 6A, 6B, 6C, and 6D (27.0, 20.1, 5.7, and 5.7%, respectively). Multilocus sequence typing revealed that clonal complex (CC) 90, including ST90 and its variants, was the most prevalent clonal group of "putative serotype 6E" isolates (n = 63; 62.4%). CC146 and CC315 were also found frequently in some of the countries. Most of the "putative serotype 6E" isolates showed very high resistance rates against cefuroxime, erythromycin, azithromycin, clarithromycin, clindamycin, and trimethoprim/sulfamethoxazole, probably due to their highly resistant to antimicrobials clone, CC90. Our results indicate that "putative serotype 6E" is prevalent in Asian countries. The clonal dissemination of "putative serotype 6E" isolates was also identified.

DFT study on X⁻·(H2O)(n=1-10) (X=OH, NO2, NO3, CO3) anionic water cluster.

A theoretical study to understand the interaction between anion and the water molecules through the hydration (X(-)·(H2O)n (X=OH, NO2, NO3, CO3), where n=1-10), using the density functional theory method with B3LYP functional and 6-311++G(d,p) basis set has been carried out systematically. In these hydrated clusters we notice three different cases of bond arrangements, namely, symmetrical double hydrogen bond, single hydrogen bond and inter-water hydrogen bond. All the complexes are dominated by the O-H⋯O hydrogen bond, in which the anion act as a proton acceptor, while the water molecule act as a proton donor. A linear correlation is obtained between the solvent stabilization energy and the size (n) of the hydrated cluster for all the anions. The weighted average interaction energy values, shows that the water molecules strongly bind with the OH(-) anion. Besides, the solvation of the OH(-) anion requires less number of water molecules when compared with the other anions. Energy decomposition analysis (EDA) shows the strong dominance of the electrostatic energy component within the interaction energy. The total NPA charges on the anions indicate an increase in the solvation due to hydration. From AIM analysis, excellent linear inverse correlation is observed for both the electron density and Laplacian of the electron density with respect to the hydrogen bond length. Natural bonding orbital analysis (NBO) predicts large charge transfer between the OH(-) anion and the water molecules.

Spread of carbapenem-resistant Acinetobacter baumannii global clone 2 in Asia and AbaR-type resistance islands.

In this surveillance study, we identified the genotypes, carbapenem resistance determinants, and structural variations of AbaR-type resistance islands among carbapenem-resistant Acinetobacter baumannii (CRAB) isolates from nine Asian locales. Clonal complex 92 (CC92), corresponding to global clone 2 (GC2), was the most prevalent in most Asian locales (83/108 isolates; 76.9%). CC108, or GC1, was a predominant clone in India. OXA-23 oxacillinase was detected in CRAB isolates from most Asian locales except Taiwan. blaOXA-24 was found in CRAB isolates from Taiwan. AbaR4-type resistance islands, which were divided into six subtypes, were identified in most CRAB isolates investigated. Five isolates from India, Malaysia, Singapore, and Hong Kong contained AbaR3-type resistance islands. Of these, three isolates harbored both AbaR3- and AbaR4-type resistance islands simultaneously. In this study, GC2 was revealed as a prevalent clone in most Asian locales, with the AbaR4-type resistance island predominant, with diverse variants. The significance of this study lies in identifying the spread of global clones of carbapenem-resistant A. baumannii in Asia.

Dissemination of metallo-ß-lactamase-producing Pseudomonas aeruginosa of sequence type 235 in Asian countries.

OBJECTIVES: To investigate the epidemiological traits of metallo-ß-lactamase (MBL)-producing Pseudomonas aeruginosa (MPPA) clinical isolates collected by the Asian Network for Surveillance of Resistant Pathogens (ANSORP). METHODS: A total of 16 MPPA clinical isolates were collected from six Asian countries in 2000 to 2009 by ANSORP. The MBL gene was detected by PCR amplification. The genetic organization of the class 1 integron carrying the MBL gene cassette was investigated by PCR mapping and sequencing. Southern blotting, repetitive sequence-based PCR and multilocus sequence typing (MLST) experiments were performed to characterize the isolates. RESULTS: PCR and sequencing experiments detected the blaVIM-2 (n = 12), blaVIM-3 (n = 1), blaIMP-6 (n = 2) and blaIMP-26 (n = 1) genes. The MBL genes were located on the chromosome in all isolates except one. Furthermore, all the MBL genes were located in a class 1 integron. All the MPPA isolates from Malaysia, Thailand, Sri Lanka and Korea were identified as sequence type (ST) 235 by MLST. Three VIM-2-producing isolates from India were identified as ST773, and one isolate harbouring VIM-3 from Taiwan was identified as ST298. CONCLUSIONS: P. aeruginosa ST235 might play a role in dissemination of MBL genes in Asian countries.

Nasopharyngeal swabs of school children, useful in rapid assessment of community antimicrobial resistance patterns in Streptococcus pneumoniae and Haemophilus influenzae.

OBJECTIVES: The present study evaluates the feasibility of rapid surveillance of community antimicrobial resistance (AMR) patterns of Streptococcus pneumoniae and Haemophilus influenzae in India using nasopharyngeal swabs (NPSs) of school children. It compares the AMR data obtained with that of invasive and nasopharyngeal (NP) isolates studied previously. No one has done such surveillance since our study so we decided to publish and more clearly demonstrate the feasibility of the methodology we did. STUDY DESIGN AND SETTING: This community-based, cross-sectional, cluster sample study had seven centers; each had two sites distant to them. Two hundred sixty school children per center were enrolled. NP swabbing was performed and isolates identified as S. pneumoniae and H. influenzae at each center were sent to reference laboratories. RESULTS: From January to December 2004, 1,988 NP swabs were processed; 776 S. pneumoniae and 64 H. influenzae were isolated. The AMR patterns for S. pneumoniae to co-trimoxazole varied, with sensitivity as low as 6% in Mumbai, 29% in Chennai and Vellore, and 100% in Delhi and Lucknow. For H. influenzae, sensitivity rates to co-trimoxazole ranged from 22% to 62%. The AMR patterns for both bacteria in the present study with data from invasive and NP isolates studied earlier were similar. CONCLUSION: The study demonstrates that it is practical and feasible to rapidly assess the AMR patterns of both S. pneumoniae and H. influenzae in NPSs of school children in different geographic locations all over India.

Changing trends in antimicrobial resistance and serotypes of Streptococcus pneumoniae isolates in Asian countries: an Asian Network for Surveillance of Resistant Pathogens (ANSORP) study.

Antimicrobial resistance in Streptococcus pneumoniae remains a serious concern worldwide, particularly in Asian countries, despite the introduction of heptavalent pneumococcal conjugate vaccine (PCV7). The Asian Network for Surveillance of Resistant Pathogens (ANSORP) performed a prospective surveillance study of 2,184 S. pneumoniae isolates collected from patients with pneumococcal infections from 60 hospitals in 11 Asian countries from 2008 to 2009. Among nonmeningeal isolates, the prevalence rate of penicillin-nonsusceptible pneumococci (MIC, ≥ 4 µg/ml) was 4.6% and penicillin resistance (MIC, ≥ 8 µg/ml) was extremely rare (0.7%). Resistance to erythromycin was very prevalent in the region (72.7%); the highest rates were in China (96.4%), Taiwan (84.9%), and Vietnam (80.7%). Multidrug resistance (MDR) was observed in 59.3% of isolates from Asian countries. Major serotypes were 19F (23.5%), 23F (10.0%), 19A (8.2%), 14 (7.3%), and 6B (7.3%). Overall, 52.5% of isolates showed PCV7 serotypes, ranging from 16.1% in Philippines to 75.1% in Vietnam. Serotypes 19A (8.2%), 3 (6.2%), and 6A (4.2%) were the most prominent non-PCV7 serotypes in the Asian region. Among isolates with serotype 19A, 86.0% and 79.8% showed erythromycin resistance and MDR, respectively. The most remarkable findings about the epidemiology of S. pneumoniae in Asian countries after the introduction of PCV7 were the high prevalence of macrolide resistance and MDR and distinctive increases in serotype 19A.

High prevalence of multidrug-resistant nonfermenters in hospital-acquired pneumonia in Asia.

RATIONALE: Hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) remain important causes of morbidity and mortality. Increasing antimicrobial resistance has aroused the concern of the failure of antibiotic treatment. OBJECTIVES: To determine the distribution of the bacterial isolates of HAP and VAP, their antimicrobial resistance patterns, and impact of discordant antibiotic therapy on clinical outcome in Asian countries METHODS: A prospective surveillance study was conducted in 73 hospitals in 10 Asian countries from 2008-2009. A total of 2,554 cases with HAP or VAP in adults were enrolled and 2,445 bacterial isolates were collected from 1,897 cases. Clinical characteristics and antimicrobial resistance profiles were analyzed. MEASUREMENT AND MAIN RESULTS: Major bacterial isolates from HAP and VAP cases in Asian countries were Acinetobacter spp., Pseudomonas aeruginosa, Staphylococcus aureus, and Klebsiella pneumoniae. Imipenem resistance rates of Acinetobacter and P. aeruginosa were 67.3% and 27.2%, respectively. Multidrug-resistant rates were 82% and 42.8%, and extensively drug-resistant rates were 51.1% and 4.9%. Multidrug-resistant rate of K. pneumoniae was 44.7%. Oxacillin resistance rate of S. aureus was 82.1%. All-cause mortality rate was 38.9%. Discordant initial empirical antimicrobial therapy increased the likelihood of pneumonia-related mortality (odds ratio, 1.542; 95% confidence interval, 1.127-2.110). CONCLUSIONS: Acinetobacter spp., P. aeruginosa, S. aureus, and K. pneumoniae are the most frequent isolates from adults with HAP or VAP in Asian countries. These isolates are highly resistant to major antimicrobial agents, which could limit the therapeutic options in the clinical practice. Discordant initial empirical antimicrobial therapy significantly increases the likelihood of pneumonia-related mortality.

Spread of methicillin-resistant Staphylococcus aureus between the community and the hospitals in Asian countries: an ANSORP study.

OBJECTIVES: Methicillin-resistant Staphylococcus aureus (MRSA) is highly prevalent in hospitals in many Asian countries. Recent emergence of community-associated (CA) MRSA worldwide has added another serious concern to the epidemiology of S. aureus infections. To understand the changing epidemiology of S. aureus infections in Asian countries, we performed a prospective, multinational surveillance study with molecular typing analysis. METHODS: We evaluated the prevalence of methicillin resistance in S. aureus isolates in CA and healthcare-associated (HA) infections, and performed molecular characterization and antimicrobial susceptibility tests of MRSA isolates. RESULTS: MRSA accounted for 25.5% of CA S. aureus infections and 67.4% of HA infections. Predominant clones of CA-MRSA isolates were ST59-MRSA-SCCmec type IV-spa type t437, ST30-MRSA-SCCmec type IV-spa type t019 and ST72-MRSA-SCCmec type IV-spa type t324. Previously established nosocomial MRSA strains including sequence type (ST) 239 and ST5 clones were found among CA-MRSA isolates from patients without any risk factors for HA-MRSA infection. CA-MRSA clones such as ST59, ST30 and ST72 were also isolated from patients with HA infections. CONCLUSIONS: Our findings confirmed that MRSA infections in the community have been increasing in Asian countries. Data also suggest that various MRSA clones have spread between the community and hospitals as well as between countries.