Severe Community-acquired Infections Research Articles

Genomic evolution of Klebsiella pneumoniae clones: the good, the bad and the ugly

Klebsiella pneumoniae (Kp) is an infamous cause of multi-drug resistant (MDR) healthcare-associated infections and several MDR clones are globally distributed. A small number of drug-susceptible clones have also become globally distributed, causing severe community-acquired infections. These ‘hypervirulent’ clones are distinguished by expression of highly serum-resistant K1/K2 capsules, plus high prevalence of acquired virulence determinants. While hypervirulence and drug resistance are usually mutually exclusive, there are now increasing reports of convergent strains that are both highly virulent and MDR – a potentially disastrous combination. To better understand the risks of MDR-virulence convergence, we leveraged a collection of >2200 Kp genomes to identify 28 common clones (n≥10 genomes each), and performed a genomic evolutionary comparison. Eight MDR and 6 hypervirulent clones were identified by acquired resistance and virulence gene prevalence. Chromosomal recombination, capsule locus diversity, pan-genome, plasmid and phage dynamics were compared. MDR clones were highly diverse, with frequent chromosomal recombination generating extensive capsule locus diversity. Additional pan-genome diversity was driven by frequent acquisition/loss of both plasmids and phage. In contrast, chromosomal recombination was rare in the hypervirulent clones, which were each associated with only a single capsule locus and showed significant reduction in pan-genome diversity, largely driven by a reduction in plasmid diversity. These data suggest that hypervirulent clones are subject to some sort of constraint for horizontal gene-transfer. Hence we predict MDR clones pose the greatest risk for MDR-virulence convergence because they are more likely to acquire virulence genes than hypervirulent clones are to acquire resistance genes.

Complement Susceptibility in Relation to Genome Sequence of Recent Klebsiella pneumoniae Isolates from Thai Hospitals.

The capacity to resist the bactericidal action of complement (C') is a strong but poorly understood virulence trait in Klebsiella spp. Killing requires activation of one or more C' pathways, assembly of C5b-9 membrane attack complexes (MACs) on the surface of the outer membrane (OM), and penetration of MACs into the target bilayer. We interrogated whole-genome sequences of 164 Klebsiella isolates from three tertiary hospitals in Thailand for genes encoding surface-located macromolecules considered to play a role in determination of C' resistance. Most isolates (154/164) were identified as Klebsiella pneumoniae, and the collection conformed to previously established population structures and antibiotic resistance patterns. The distribution of sequence types (STs) and capsular (K) types were also typical of global populations. The majority (64%) of isolates were resistant to C', and the remainder were either rapidly or slowly killed. All isolates carried genes encoding capsular polysaccharides (K antigens), which have been strongly linked to C' resistance. In contrast to previous reports, there were no differences in the amount of capsule produced by C'-resistant isolates compared to C'-susceptible isolates, nor was there any correlation between serum reactivity and the presence of hypermucoviscous capsules. Similarly, there were no correlations between the presence of genes specifying lipopolysaccharide O-side chains or major OM proteins. Some virulence factors were found more frequently in C'-resistant isolates but were considered to reflect clonal ST expansion. Thus, no single gene accounts for the C' resistance of the isolates sequenced in this study.IMPORTANCE Multidrug-resistant Klebsiella pneumoniae is responsible for an increasing proportion of nosocomial infections, and emerging hypervirulent K. pneumoniae clones now cause severe community-acquired infections in otherwise healthy individuals. These bacteria are adept at circumventing immune defenses, and most survive and grow in serum; their capacity to avoid C'-mediated destruction is correlated with their invasive potential. Killing of Gram-negative bacteria occurs following activation of the C' cascades and stable deposition of C5b-9 MACs onto the OM. For Klebsiella, studies with mutants and conjugants have invoked capsules, lipopolysaccharide O-side chains, and OM proteins as determinants of C' resistance, although the precise roles of the macromolecules are unclear. In this study, we sequenced 164 Klebsiella isolates with different C' susceptibilities to identify genes involved in resistance. We conclude that no single OM constituent can account for resistance, which is likely to depend on biophysical properties of the target bilayer.

A Dual-Replicon Shuttle Vector System for Heterologous Gene Expression in a Broad Range of Gram-Positive and Gram-Negative Bacteria.

Origin of replication (ori in theta-replicating plasmids or dso in rolling circle replicating plasmids) initiates plasmid replication in a broad range of bacteria. These two kinds of plasmids were both identified in Streptococcus, a genus composed of both human commensal bacteria and pathogens with the ability to cause severe community-acquired infections, including meningitides, septicemia, and respiratory tract diseases. Given the important roles of Streptococcus in the exchange of genetic elements with other symbiotic microbes, the genotypes and phenotypes of both Streptococcus spp. and other symbiotic species could be changed during colonization of the host. Therefore, an improved plasmid system is required to study the functional, complicated, and changeable genomes of Streptococcus. In this study, a dual-replicon shuttle vector system named pDRE was constructed to achieve heterologous gene expression. The vector system contained theta replicon for Escherichia coli. The origin of rolling circle replicon was synthesized according to pMV158 in Gram-positive bacteria. By measuring the products of inserted genes at multiple cloning sites, the ability of this vector system in the replication and expression of heterologous genes was assessed in four Streptococcus and three other Gram-positive bacteria: Bacillus subtilis, Lactococcus lactis, and Staphylococcus aureus. The results showed that the newly constructed vector could simultaneously replicate and express heterologous genes in a broad range of Gram-positive and Gram-negative bacteria, thus providing a potentially powerful genetic tool for further functional analysis.

Cost-effectiveness of a potential vaccine candidate for Haemophilus influenzae serotype ‘a’

The preceding decade has witnessed the emergence of severe community-acquired acute infections caused by Haemophilus influenzae serotype a (Hia), with alarming incidence rates in North America, particularly among indigenous populations. The remarkable success of Hib conjugate vaccine over the past 20 years signify the development of an Hia vaccine candidate as a prevention measure to reduce the incidence of invasive Hia disease. However, quantifications of the long-term epidemiologic and economic impacts of vaccination are needed to inform decision on investment in Hia vaccine development and immunization programs. We sought to evaluate the cost-effectiveness of an Hia vaccine with a similar routine infant immunization schedules currently in practice for Hib in Canada. We developed and parameterized an agent-based simulation model using age-specific incidence rates reported for Nunavut, a Canadian territory with predominantly aboriginal populations. Our results, based on statistical analyses of the incremental cost-effectiveness ratio, show that an Hia conjugate vaccine is highly cost-effective. Sustaining an immunization program with vaccine coverages of 77% for primary series and 93% for booster dose over a 10-year period reduces the incidence of invasive disease by 63.8% on average from 9.97 to 3.61 cases, per 100,000 population. The overall costs of disease management in year 10 are reduced by 53.4% from CDN $1.863 million (95% CI: $1.229–$2.519 M) to CDN $0.868 million (95% CI: $0.627–$1.120 M). The findings suggest an important role for a conjugate vaccine in managing Hia disease as a growing public health threat.

The pilgrimage and the burden of pneumococcal disease in adults

Pneumococcal disease is responsible for significant morbidity and mortality. All over the world, 1.6 million people die of pneumococcal disease every year; this estimate includes the deaths of 1 million children aged less than 5 years and the deaths of 600.000- 800.000 adults. The burden of pneumococcal disease is high in adults. Increasing age and the presence of comorbidity has a significant affected of the risk of developing the disease. During mass gatherings, such as pilgrimage individuals, is exposed to severe community-acquired pneumococcal infections. Individuals who has Streptococcus pneumoniae in nasopharynx, have the potential to infection and leave exposed to the risk of pneumococcal disease the other Individuals with sneezing, coughing or out of breath, given breath through droplets of these microorganisms. In the present review, the relationship of pneumococcal disease in adults and pilgrimage, vaccination strategies will be considered and then during a visit to Pilgrimate and Umrah pilgrims against the current vaccine recommendations will be summarised.

Adjunctive rifampicin for Staphylococcus aureus bacteraemia (ARREST): a multicentre, randomised, double-blind, placebo-controlled trial

SummaryBackgroundStaphylococcus aureus bacteraemia is a common cause of severe community-acquired and hospital-acquired infection worldwide. We tested the hypothesis that adjunctive rifampicin would reduce bacteriologically confirmed treatment failure or disease recurrence, or death, by enhancing early S aureus killing, sterilising infected foci and blood faster, and reducing risks of dissemination and metastatic infection.MethodsIn this multicentre, randomised, double-blind, placebo-controlled trial, adults (≥18 years) with S aureus bacteraemia who had received ≤96 h of active antibiotic therapy were recruited from 29 UK hospitals. Patients were randomly assigned (1:1) via a computer-generated sequential randomisation list to receive 2 weeks of adjunctive rifampicin (600 mg or 900 mg per day according to weight, oral or intravenous) versus identical placebo, together with standard antibiotic therapy. Randomisation was stratified by centre. Patients, investigators, and those caring for the patients were masked to group allocation. The primary outcome was time to bacteriologically confirmed treatment failure or disease recurrence, or death (all-cause), from randomisation to 12 weeks, adjudicated by an independent review committee masked to the treatment. Analysis was intention to treat. This trial was registered, number ISRCTN37666216, and is closed to new participants.FindingsBetween Dec 10, 2012, and Oct 25, 2016, 758 eligible participants were randomly assigned: 370 to rifampicin and 388 to placebo. 485 (64%) participants had community-acquired S aureus infections, and 132 (17%) had nosocomial S aureus infections. 47 (6%) had meticillin-resistant infections. 301 (40%) participants had an initial deep infection focus. Standard antibiotics were given for 29 (IQR 18–45) days; 619 (82%) participants received flucloxacillin. By week 12, 62 (17%) of participants who received rifampicin versus 71 (18%) who received placebo experienced treatment failure or disease recurrence, or died (absolute risk difference −1·4%, 95% CI −7·0 to 4·3; hazard ratio 0·96, 0·68–1·35, p=0·81). From randomisation to 12 weeks, no evidence of differences in serious (p=0·17) or grade 3–4 (p=0·36) adverse events were observed; however, 63 (17%) participants in the rifampicin group versus 39 (10%) in the placebo group had antibiotic or trial drug-modifying adverse events (p=0·004), and 24 (6%) versus six (2%) had drug interactions (p=0·0005).InterpretationAdjunctive rifampicin provided no overall benefit over standard antibiotic therapy in adults with S aureus bacteraemia.FundingUK National Institute for Health Research Health Technology Assessment.

Complete Genome Sequence of a Divergent Human Rhinovirus C Isolate from an Infant with Severe Community-Acquired Pneumonia in Colorado, USA.

ABSTRACTHere, we report the genome sequence of a divergent human rhinovirus C isolate identified from an infant with a severe community-acquired respiratory infection. RNA sequencing performed on an Illumina platform identified reads aligning to human rhinovirus species, which were de novo assembled to produce a coding-complete genome sequence.

Identifying and characterizing preventable adverse drug events for prioritizing pharmacist intervention in hospitals.

The approach and results for identifying and characterizing preventable adverse drug events (pADEs) that are key targets for pharmacist medication therapy management (MTM) are summarized. This study was part of a larger effort aimed at developing an electronic health record-based prediction model (the complexity score, or C-score) that ranks hospitalized patients according to their risk for pADEs. An environmental scan of published epidemiologic pADE studies and national patient safety priority areas was conducted. The final list of candidate pADEs was then disseminated to ASHP members and a national technical expert panel (TEP) to evaluate the importance, prevalence, severity, preventability, and measurability of these pADEs. Polychoric correlation tests were performed to evaluate and quantify associations between importance and any of the constructs' mean rankings for each individual pADE. The environmental scan yielded a total of 21 candidate pADEs, including drug-induced acute kidney injury, falls, respiratory depression, altered mental status, hemorrhage, hepatic failure, hypoglycemia, seizures, hypotension and bradycardia, ileus, blood dyscrasias, severe electrolyte imbalances, prolonged hyperglycemia, uncontrolled hypertension, uncontrolled arrhythmia, stress ulcers, hospital-acquired infections, uncontrolled hospital-acquired or community-acquired infection, uncontrolled pain, and venous thromboembolism. The survey confirmed all pADEs were important. Ranking of overall importance was mainly driven by perceived pADE severity and, to a lesser extent, by preventability and prevalence ratings. A literature review and survey of ASHP and TEP members were used to compile a list of important hospital-acquired pADEs for incorporation into a model for prioritizing patients for MTM services.

JAID/JSC Guidelines for Infection Treatment 2015-Intestinal infections.

JAID/JSC Guidelines for Infection Treatment 2015-Intestinal infections.

Sepsis Caused by Achromobacter Xylosoxidans in a Child with Cystic Fibrosis and Severe Lung Disease

Patient: Female, 10Final Diagnosis: SepsisSymptoms: Fever • hypotension • not tollerating enteral feeds • respiratory deteriorationMedication: —Clinical Procedure: IV antibiotics • lungtransplantionSpecialty: Pediatrics and NeonatologyObjective:Unusual clinical courseBackground:Achromobacter xylosoxidans is an aerobic, motile, Gram-negative, opportunistic pathogen that can be responsible for various severe nosocomial and community-acquired infections. It has been found in immunocompromised patients and patients with several other underlying conditions, but the clinical role of this microorganism in cystic fibrosis is unclear.Case Report:We describe a case of septic shock caused by A. xylosoxidans in a 10-year-old child with cystic fibrosis and severe lung disease.Conclusions:As the prevalence of A. xylosoxidans in cystic fibrosis patients is rising and patient-to-patient transmission is highly probable, further studies are warranted to determine its role and to document the appropriate treatment strategy for eradication and long-term treatment of this organism.

Severe Community-Acquired Bloodstream Infection withAcinetobacter ursingiiin Person who Injects Drugs

We report a community-acquired bloodstream infection with Acinteobacter ursingii in an HIV-negative woman who injected drugs. The infection was successfully treated with meropenem. Species identification was performed by using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Improved identification of Acinetobacter spp. by using this method will help identify clinical effects of this underdiagnosed pathogen.

Bacteremic community-acquired infections due to Klebsiella pneumoniae: clinical and microbiological presentation in New Caledonia, 2008-2013.

To provide data on severe bacteremic community-acquired infections due to Klebsiella pneumoniae in New Caledonia. All patients admitted with bacteremic community-acquired infections due to K. pneumoniae at the only tertiary medical center in New Caledonia, from 2008 to 2013, were included retrospectively in this study. Clinical and microbiological characteristics were analyzed, as well as risk factors for mortality. The characteristics of 119 patients were analyzed. The most common clinical presentation was urinary tract infection (40 cases, 33%), followed by pneumonia (28 cases, 23%), deep abscesses (15 cases, 13%), liver abscess (12 cases, 9%), meningitis in (five cases, 4%), and endophthalmitis (two cases, 1%). Multiple localizations were reported in 18 cases (15%) and isolated bacteremia was reported in 22 cases (18%). The overall mortality rate was 22% (26/119) and the mortality rate in the intensive care unit was 33% (14/42). Renal impairment, chronic liver disease, pneumonia, and isolated bacteremia were independent risk factors for mortality. K. pneumoniae is a dominant cause of severe community-acquired bacteremic infection in New Caledonia. Physicians should be aware of the poor prognosis of any patient with a bacteremic K. pneumoniae infection and should monitor patients presenting with risk factors closely.

Clinical and molecular characteristics of bloodstream infection caused by K. pneumonia

Objective To investigate the clinical features and molecular characteristics of bacteremia caused by K. pneumoniae and study on the differences between classical and hypervirulent K. pneumonia(hvKP). Methods The clinical features of 70 cases of K. pneumoniae bacteremia collected from Beijing Chaoyang Hospital from 2008 to 2012 were retrospectively analyzed. The patients were identified according to the records from the Clinical Microbiology Department. Patients' data were obtained from medical records. The molecular characteristics of the K. pneumoniae strains were also studied using PCR, multilocus sequence typing and pulsed field gel electrophoresis(PFGE) methods. Data were analyzed using the statistical package SPSS for windows version 17.0. For categorical data, different groups were compared using the Chi-square test to analyze the quantitative variables. P≤0.05 was considered to be statistically significant. All susceptibility data were analyzed using Whonet, version 5.6. Results The hvKP was identified from 31.4% of the patients with K. pneumoniae bacteremia, which displayed 4 serotypes (K1, K2, K20, and K57). About 40.9% (9/22) hypervirulent strains were isolated from patients without underlying diseases, while 95.8% (46/48) of the classic K. pneumoniae infections were found in patients with the presence of one or more underlying diseases. More hvKP positive patients (95.5%, 21/22) had community-acquired infections compared with classical K. pneumonia (cKP) infected patients (35.4%, 17/48). There was a significant difference between these two groups (χ2=21.912, P<0.001). Two ESBLs-producing hvKP strains were found. The 22 hvKP isolates had 14 different PFGE patterns, among which 6 isolates (patients with primary liver abscess) shared similar PFGE patterns. Conclusions The emerging hvKP was prevalent in patients with severe community-acquired infections in healthy individuals. Two ESBLs-producing hvKP strains were identified. Drug resistance had a rising trend, which called for more attention in clinical settings. (Chin J Lab Med, 2015, 38: 627-631) Key words: Liver abscess; Community-acquired infections; Klebsiella pneumoniae; Virulence

Mapping the Evolution of Hypervirulent Klebsiella pneumoniae.

ABSTRACTHighly invasive, community-acquired Klebsiella pneumoniae infections have recently emerged, resulting in pyogenic liver abscesses. These infections are caused by hypervirulent K. pneumoniae (hvKP) isolates primarily of capsule serotype K1 or K2. Hypervirulent K1 isolates belong to clonal complex 23 (CC23), indicating that this clonal lineage has a specific genetic background conferring hypervirulence. Here, we apply whole-genome sequencing to a collection of K. pneumoniae isolates to characterize the phylogenetic background of hvKP isolates with an emphasis on CC23. Most of the hvKP isolates belonged to CC23 and grouped into a distinct monophyletic clade, revealing that CC23 is a unique clonal lineage, clearly distinct from nonhypervirulent strains. Separate phylogenetic analyses of the CC23 isolates indicated that the CC23 lineage evolved recently by clonal expansion from a single common ancestor. Limited grouping according to geographical origin was observed, suggesting that CC23 has spread globally through multiple international transmissions. Conversely, hypervirulent K2 strains clustered in genetically unrelated groups. Strikingly, homologues of a large virulence plasmid were detected in all hvKP clonal lineages, indicating a key role in K. pneumoniae hypervirulence. The plasmid encodes two siderophores, aerobactin and salmochelin, and RmpA (regulator of the mucoid phenotype); all these factors were found to be restricted to hvKP isolates. Genomic comparisons revealed additional factors specifically associated with CC23. These included a distinct variant of a genomic island encoding yersiniabactin, colibactin, and microcin E492. Furthermore, additional novel genomic regions unique to CC23 were revealed which may also be involved in the increased virulence of this important clonal lineage.

Genomic analysis of diversity, population structure, virulence, and antimicrobial resistance in Klebsiella pneumoniae, an urgent threat to public health

Klebsiella pneumoniae is now recognized as an urgent threat to human health because of the emergence of multidrug-resistant strains associated with hospital outbreaks and hypervirulent strains associated with severe community-acquired infections. K. pneumoniae is ubiquitous in the environment and can colonize and infect both plants and animals. However, little is known about the population structure of K. pneumoniae, so it is difficult to recognize or understand the emergence of clinically important clones within this highly genetically diverse species. Here we present a detailed genomic framework for K. pneumoniae based on whole-genome sequencing of more than 300 human and animal isolates spanning four continents. Our data provide genome-wide support for the splitting of K. pneumoniae into three distinct species, KpI (K. pneumoniae), KpII (K. quasipneumoniae), and KpIII (K. variicola). Further, for K. pneumoniae (KpI), the entity most frequently associated with human infection, we show the existence of >150 deeply branching lineages including numerous multidrug-resistant or hypervirulent clones. We show K. pneumoniae has a large accessory genome approaching 30,000 protein-coding genes, including a number of virulence functions that are significantly associated with invasive community-acquired disease in humans. In our dataset, antimicrobial resistance genes were common among human carriage isolates and hospital-acquired infections, which generally lacked the genes associated with invasive disease. The convergence of virulence and resistance genes potentially could lead to the emergence of untreatable invasive K. pneumoniae infections; our data provide the whole-genome framework against which to track the emergence of such threats.

Clinical and molecular characteristics of emerging hypervirulent Klebsiella pneumoniae bloodstream infections in mainland China.

Recently, the newly emerged hypervirulent Klebsiella pneumoniae strain (hvKP) has caused great concern globally, but the clinical features and molecular characteristics of bacteremia caused by hvKP are rarely reported in mainland China. Seventy patients with K. pneumoniae bacteremia were investigated to study the clinical features of hvKP infection from 2008 till 2012 in Beijing Chao-Yang Hospital. The molecular characteristics of the hvKP strains were also studied using PCR, multilocus sequence typing, and pulsed-field gel electrophoresis (PFGE) methods. hvKP was identified in 31.4% of the patients with K. pneumoniae bacteremia, which displayed 4 serotypes (K1, K2, K20, and K57). Patients with hvKP infection tended to have no underlying diseases compared to those with classic K. pneumoniae (cKP). More hvKP-positive patients (95.5%) had community-acquired infection than did cKP-infected patients (35.4%) (P<0.001). The 30-day mortality rate was lower in hvKP-infected patients than in cKP-infected patients (4.5% compared to 16.7%). Resistance to tested antimicrobials was significantly greater in cKP- than in hvKP-infected patients. Two extended-spectrum-beta-lactamase (ESBL)-producing hvKP strains were found. Seven novel sequence types (STs) and 4 new alleles of K. pneumoniae were revealed. A strong correlation was found between two STs (ST23, ST1265) and the K1 serotype. The hvKP isolates (n=22) had 14 different PFGE patterns, and among them 10 K1 isolates shared similar PFGE patterns. The emerging hvKP strain was prevalent in patients with severe community-acquired infections in healthy individuals in China. Identification of ESBL-producing hvKP strains in hvKP-infected patients will facilitate clinical management of hvKP infection.

Pandemic influenza A(H1)pdm09 in hospitals and intensive care units – results from a new hospital surveillance, Germany 2009/2010

The pandemic influenza A(H1)pdm09 (PI) was introduced to Germany in April 2009. The Robert Koch Institute (RKI) implemented a nationwide voluntary hospital sentinel surveillance for to assess the burden and severity of PI. Three modules were offered: a hospital module collected aggregated data from all hospital units on admissions and fatalities with and without PI; an intensive care module data on admissions, patient-days, and ventilated patient-days with and without PI; and a case-based module retrieved clinical patient data of PI cases. A in-patient with a PCR confirmation was defined as a PI case. Descriptive, trend, uni-, and multivariable analysis were performed. Between week 49/2009 and 13/2010, the hospitals reported 103 (0.07%) PI cases among 159181 admissions and 59/16728 (0.35%) PI-related admissions in intensive care units (ICUs). The weekly average incidence decreased in hospitals by 21.5% and in ICUs by 19.2%. In ICUs, 1848/85559 (2.2%) patient-days were PI-related, 94.8% of those with mechanical ventilation. Case-based data on 43 recovered and 16 fatal PI cases were reported. Among recovered, 61% were admitted to ICUs, 51% were mechanically ventilated, and 16% received extracorporeal membrane oxygenation (ECMO). All fatal cases were admitted to ICUs and received mechanical ventilation, 75% ECMO. Fatal outcome was rather associated with complications than with underlying medical conditions. The surveillance started shortly after the PI peak, which explains the small number of PI cases. The burden of PI disease was low, but higher in ICUs with a high proportion of severe cases needing ventilation and ECMO treatment. A continuous hospital surveillance system could be helpful to measure the burden of severe community-acquired infections.

Role of the (Mn)superoxide dismutase of Enterococcus faecalis in the in vitro interaction with microglia

Enterococcus faecalis is a significant human pathogen worldwide and is responsible for severe nosocomial and community-acquired infections. Although enterococcal meningitis is rare, mortality is considerable, reaching 21 %. Nevertheless, the pathogenetic mechanisms of this infection remain poorly understood, even though the ability of E. faecalis to avoid or survive phagocytic attack in vivo may be very important during the infection process. We previously showed that the manganese-cofactored superoxide dismutase (MnSOD) SodA of E. faecalis was implicated in oxidative stress responses and, interestingly, in the survival within mouse peritoneal macrophages using an in vivo-in vitro infection model. In the present study, we investigated the role of MnSOD in the interaction of E. faecalis with microglia, the brain-resident macrophages. By using an in vitro infection model, murine microglial cells were challenged in parallel with the wild-type strain JH2-2 and its isogenic sodA deletion mutant. While both strains were phagocytosed by microglia efficiently and to a similar extent, the ΔsodA mutant was found to be significantly more susceptible to microglial killing than JH2-2, as assessed by the antimicrobial protection assay. In addition, a significantly higher percentage of acidic ΔsodA-containing phagosomes was found and these also underwent enhanced maturation as determined by the expression of endolysosomal markers. In conclusion, these results show that the MnSOD of E. faecalis contributes to survival of the bacterium in microglial cells by influencing their antimicrobial activity, and this could even be important for intracellular killing in neutrophils and thus for E. faecalis pathogenesis.

Prevalence and characterization of methicillin-resistant Staphylococcus aureus among healthy children in a city of Argentina

Community acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) is a major global problem. Healthy carriers of S. aureus strains have an important role in the dissemination of this bacterium. The aim of this study was to estimate the prevalence of S. aureus and methicillin-resistant S. aureus (MRSA) carriage among healthy children in a city of Buenos Aires province, Argentina, and to determine the potential risk factors for its acquisition. We also described the molecular features of MRSA strains circulating in this population. S. aureus carriage was investigated in all children attending the last year of kindergarten during the 2008 school- year period. Household contacts of MRSA carriers were also screened. Of 316 healthy children, 98 (31.0%) carried S. aureus, including 14 MRSA carriers (4.4%) and 84 methicillin susceptible S. aureus (MSSA) carriers (26.6%). All MRSA isolates carried the SCC mec type IV cassette. Eight of the fourteen isolates were closely related to the clone responsible for most severe community-acquired MRSA infections caused in our country (CAA: PFGE A, SCC mec IV, spa t311, ST5). Two subtypes (A 1 and A 2) were distinguished in this group by PFGE. Both had agr type II and presented the same virulence determinants, except for PVL coding genes and sea that were only harbored by subtype A 1. Our results, based on the analysis of MRSA isolates recovered in the screening of healthy children, provide evidence of a community reservoir of the major CA-MRSA clone described in Argentina.

Relación Entre Virulencia y Resistencia Antimicrobiana en/ Relationship Between Virulence and Antimicrobial Resistance in

Acinetobacter baumanni causa frecuentemente infecciones intrahospitalarias y actualmente se ha relacionado con el desarrollo de infecciones severas adquiridas en la comunidad. La capacidad de colonizar diversos hábitats y la versatilidad en su metabolismo ha influido en el incremento del número de infecciones nosocomiales, siendo responsable del desarrollo de enfermedades como: sepsis, neumonías y meningitis. Estas infecciones aparecen en forma de brotes, dominados por clones epidémicos con multirresistencia a los antibióticos que causan altas tasas de morbilidad y mortalidad. Las Unidades de Cuidados Intensivos son las más afectadas por el uso masivo de antibióticos que ocasiona la aparición de cepas multirresistentes. Es importante estudiar los mecanismos de patogénesis y la resistencia a los antibióticos, como factores directos que determinan el problema de salud.Por otra parte, las islas de patogenecidad que corresponde a material genético exógeno que ha sido integrado al genoma de la bacteria, explicaría en gran medida el carácter patogénico de la bacteria. Estas transportan genes que confieren multirresistencia a los antibióticos y son responsables directos de llevar genes involucrados en mecanismos patogénicos como son: el sistema de captación de hierro, el sistema para la formación de biopelículas en superficies abióticas, el mecanismo de formación de la proteína de membrana externa 38 y los sistemas de secreción de proteínas tipo IV, que han sido demostrados como responsables directos de la patogénesis de diversos patógenos. En este artículo se revisa la situación actual de la incidencia de las infecciones nosocomiales causadas por A. baumannii multirresistente a los antibióticos, los principales mecanismos de resistencia a fármacos y la asociación de ésta con los mecanismos de patogenicidad. El conocimiento de los elementos involucrados en la patogénesis de A. baumannii permitirá establecer los mecanismos que lleven a controlar su diseminación.