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PubMed2004

An Asian study on the prevalence of atypical respiratory pathogens in community-acquired pneumonia.

BACKGROUND: In many parts of Asia, the inaccessibility and high cost of diagnostic tests have hampered the study of community-acquired pneumonia (CAP) caused by atypical respiratory pathogens. OBJECTIVE: This surveillance study examined the frequency of infection with Mycoplasma pneumoniae, Chlamydophila pneumoniae, and Legionella pneumophila in 1756 patients presenting with signs and symptoms of CAP at 12 medical centres in Asia, using standardised laboratory techniques and interpretation criteria in all participating centres. METHODS: Diagnosis of current infection was based on significant changes in antibody titer or persisting high antibody titers, together with the presence of bacterial DNA in respiratory secretions, in the case of M. pneumoniae and C. pneumoniae infections, or bacterial antigen in urine, in the case of L. pneumophila serogroup 1 infection. RESULTS: Using these criteria, results from 1374 patients with paired sera showed that, overall, 23.5% of CAP cases were associated with infection with atypical respiratory pathogens, with M. pneumoniae, C. pneumoniae, and L. pneumophila being found in 12.2%, 4.7%, and 6.6% of cases, respectively. Persisting high antibody titers indicative of past exposure to M. pneumoniae, C. pneumoniae, and L. pneumophila were seen in 10.2%, 4.8%, and 18.9% of patients, respectively. CONCLUSION: These data reflect the overall high prevalence of these atypical pathogens among Asian patients with CAP.

Adolescent↗

PubMed2004

Emerging resistance among bacterial pathogens in the intensive care unit--a European and North American Surveillance study (2000-2002).

BACKGROUND: Globally ICUs are encountering emergence and spread of antibiotic-resistant pathogens and for some pathogens there are few therapeutic options available. METHODS: Antibiotic in vitro susceptibility data of predominant ICU pathogens during 2000-2 were analyzed using data from The Surveillance Network (TSN) Databases in Europe (France, Germany and Italy), Canada, and the United States (US). RESULTS: Oxacillin resistance rates among Staphylococcus aureus isolates ranged from 19.7% to 59.4%. Penicillin resistance rates among Streptococcus pneumoniae varied from 2.0% in Germany to as high as 20.2% in the US; however, ceftriaxone resistance rates were comparably lower, ranging from 0% in Germany to 3.4% in Italy. Vancomycin resistance rates among Enterococcus faecalis were < or = 4.5%; however, among Enterococcus faecium vancomycin resistance rates were more frequent ranging from 0.8% in France to 76.3% in the United States. Putative rates of extended-spectrum beta-lactamase (ESBL) production among Enterobacteriaceae were low, <6% among Escherichia coli in the five countries studied. Ceftriaxone resistance rates were generally lower than or similar to piperacillin-tazobactam for most of the Enterobacteriaceae species examined. Fluoroquinolone resistance rates were generally higher for E. coli (6.5% - 13.9%), Proteus mirabilis (0-34.7%), and Morganella morganii (1.6-20.7%) than other Enterobacteriaceae spp (1.5-21.3%). P. aeruginosa demonstrated marked variation in beta-lactam resistance rates among countries. Imipenem was the most active compound tested against Acinetobacter spp., based on resistance rates. CONCLUSION: There was a wide distribution in resistance patterns among the five countries. Compared with other countries, Italy showed the highest resistance rates to all the organisms with the exception of Enterococcus spp., which were highest in the US. This data highlights the differences in resistance encountered in intensive care units in Europe and North America and the need to determine current local resistance patterns by which to guide empiric antimicrobial therapy for intensive care infections.

Journal Article↗

PubMed2006

Autophagy in innate and adaptive immunity against intracellular pathogens.

Autophagy delivers cytoplasmic constituents for lysosomal degradation. Recent studies have demonstrated that this pathway mediates resistance to pathogens and is targeted for immune evasion by viruses and bacteria. Lysosomal degradation products, including pathogenic determinants, are then surveyed by the adaptive immune system to elicit antigen-specific T cell responses. CD4(+) T helper cells have been shown to recognize nuclear and cytosolic antigens via presentation by major histocompatibility complex (MHC) class II molecules after autophagy. Furthermore, some sources of natural MHC class II ligands display characteristics of autophagy substrates, and autophagosomes fuse with late endosomes, in which MHC class II loading is thought to occur. Although MHC class II antigen processing via autophagy has so far mainly been described for professional antigen-presenting cells like B cells, macrophages, and dendritic cells, it might be even more important for cells with less endocytic potential, like epithelial cells, when these express MHC class II at sites of inflammation. Therefore, autophagy might contribute to immune surveillance of intracellular pathogens via MHC class II presentation of intracellular pathogen-derived peptides.

Adaptation, Physiological↗

PubMed2003

A 5-year study of the bacterial pathogens associated with acute diarrhoea on the island of Crete, Greece, and their resistance to antibiotics.

During a 5-year period (1995-1999) a total of 7090 stool samples obtained from patients with acute diarrhoea, mostly community-acquired, were examined for bacterial pathogens, in the Greek island of Crete. One or more enteric pathogens were isolated from 987 patients (14%). Salmonella enterica were the most commonly isolated bacteria (6%), followed by Campylobacter spp. (4.2%), and enteropathogenic Escherichia coli (EPEC) (1.8%). Yersinia enterocolitica (0.6%), Shigella spp. (0.3%), and Aeromonas hydrophila (0.04%), were less frequently isolated. Clostridium difficile was isolated from 65 out of 451 diarrhoeal specimens examined (14.4%). Toxin B was detected in all cases. No verotoxigenic E. coli strains were identified. Resistance to ampicillin was observed in 31.5% of the Salmonella, 58.3% of the Shigella and 31.5% of the EPEC isolates. Resistance to trimethoprim-sulfamethoxazole was observed in 4.4% of the Salmonella, 30.5% of the Shigella, and 18.5% of the EPEC isolates. High percentages of resistance to quinolones (44.5% to norfloxacin, and 40.5% to ciprofloxacin), were found among Campylobacter isolates, while resistance to erythromycin was observed in 14.9% of them. With the present study we continue the surveillance of bacterial pathogens associated with diarrhoeal disease on the island of Crete.

Acute Disease↗

PubMed2006

Prevalence and antimicrobial susceptibility patterns among gastroenteritis-causing pathogens recovered in Europe and Latin America and Salmonella isolates recovered from bloodstream infections in North America and Latin America: report from the SENTRY Antimicrobial Surveillance Program (2003).

Gastroenteritis-causing pathogens are the second leading cause of morbidity and mortality worldwide. Complicating the clinical diarrhoea syndrome is the emergence of antimicrobial resistance among the responsible bacterial pathogens. The reported increases in fluoroquinolone resistance in Salmonella, Shigella and Campylobacter have been extremely worrisome considering the primary role of ciprofloxacin as a treatment. In this study, 1479 bacterial isolates from gastroenteritis infections were collected in Europe and Latin America, which included Salmonella spp. (834; 56%), Shigella spp. (311; 21%), Campylobacter spp. (182; 12%) and Aeromonas spp. (72; 5%). The fluoroquinolones displayed the greatest activity against these pathogens, with only three non-Campylobacter spp. strains being non-susceptible using current Clinical and Laboratory Standards Institute (CLSI) breakpoint criteria. Whilst ciprofloxacin resistance in European and Latin American Salmonella was only 0.2% and 0.0%, respectively, a total of 16.2% and 12.9% of isolates were resistant to nalidixic acid, indicating possible first-step gyrA mutations. Among confirmed extended-spectrum beta-lactamase-producing Salmonella strains, CTX-M genes were detected in 15 originating from Russia. Erythromycin and azithromycin were the most potent agents tested against Campylobacter spp. (values of minimum inhibitory concentration for 90% of the organisms, 0.5 mg/L and 0.12 mg/L, respectively), with erythromycin displaying the highest susceptibility (91.1%). Salmonella isolates from bloodstream infections displayed antibiograms that were nearly identical to strains causing gastroenteritis. Considering the role that antimicrobial therapy plays in the management of moderate to severe bacterial gastroenteritis, global surveillance and local/national public health programmes can provide critical data illuminating the dissemination of resistance and guidance for empirical therapy.

Aeromonas↗

PubMed1996

A multicentre collaborative study of the antimicrobial susceptibility of community-acquired, lower respiratory tract pathogens 1992-1993: the Alexander Project.

The Alexander Project is a unique, international, collaborative antimicrobial susceptibility surveillance study of bacterial pathogens causing community-acquired lower respiratory tract infection. Fifteen centres, ten in the European Union (EU) and five in the USA, each submitted up to 400 isolated per year for 2 years (1992 and 1993) to a central laboratory for re-identification and determination of MICs of 15 antimicrobials using the Sensititre microbroth incorporation technique. Of the total of 6385 isolates collected, Haemophilus influenzae (2718), Streptococcus pneumoniae (1856) and Moraxella catarrhalis (818) were the most frequently identified pathogens. Staphylococcus aureus (690). Haemophilus parainfluenzae (183) and Klebsiella pneumoniae (120) were identified less commonly. High-level penicillin resistance in S. pneumoniae (MIC > or = 2 mg/L) was found in 222 isolates, an overall prevalence of 12% which varied from < 1% in Germany, Italy, UK and two of the five USA centres, to 3.8-40.4% in the remainder, with the highest prevalence found in France and Spain. Intermediate penicillin resistance (MIC 0.12-1 mg/L) was identified in 228 isolates of S. pneumoniae, an overall prevalence of 12.3%, with individual centre prevalence varying widely (EU, 0-52.3%; USA, 0-20.9%) and not always following that of high-level resistance. Resistance to other, unrelated, antimicrobials, except notably the fluoroquinolones, was strongly associated with beta-lactam resistance. beta-lactamase production was detected in 492 isolates of H. influenzae, an overall prevalence of 18.1%. Rates of detection varied widely between centres from 1.4% in Weingarten, Germany in 1993 to 38.5% in Barcelona, Spain in 1992. In general, the prevalence of beta-lactamase production was higher and less variable in USA centres than in those of the EU. beta-Lactamase was detected consistently in the majority of isolates of M. catarrhalis with an overall prevalence of 81.7%. Virtually no other resistance phenotype was recognised in this species. Of the 690 collected, most isolates of S. aureus produced beta-lactamase with rates of detection varying from 52.2%-89.1%. Isolates from two centres, Genoa, Italy in 1992 and Paris, France in 1993, were associated with a high prevalence of methicillin-resistance (34.8% and 43.8%, respectively). Combined isolates of H. parainfluenzae and K. pneumoniae accounted for only 4.7% of the total collection. Although the current data are insufficient to allow analysis of trends in resistance, the study participants have continued to collect further isolates in 1994 and 1995 which will be reported in the future.

Amoxicillin↗

PubMed2003

Antimicrobial susceptibility of common bacterial pathogens isolated from a new regional hospital in southern Taiwan.

BACKGROUND: Antimicrobial resistance has become a major health problem in Taiwan. While some trends in antimicrobial resistance are universal, others appear to be unique for specific regions. METHODS: To determine the distribution and antimicrobial drug resistance of bacterial pathogens in a new hospital in southern Taiwan, surveillance data on major bacterial pathogens isolated from Chang Gung Memorial Hospital at Chia-Yi from January 2002 through December 2002 were retrospectively analyzed. RESULTS: The most common gram-positive isolate was Staphylococcus aureus. Escherichia coli and Klebsiella pneumoniae were the two most common gram negative isolates. Pseudomonas aeruginosa ranked the first among gram-negative, glucose non-fermenting isolates, followed in the order of frequency by Acinetobacter baumannii. Oxacillin resistance rate of S. aureus was 58%, while vancomycin and teicoplanin remained effective against all of the isolates. The penicillin non-susceptibility rate of Streptococcus pneumoniae was 52%, and it is notable that the rate of resistance to erythromycin was 87%. Resistance to various antimicrobial agents for P. aeruginosa, Aeromonas hydrophila, and gram-negative enteric bacilli was very common in our study. Infections caused by multidrug-resistant A. baumannii was not uncommon in this hospital but fortunately, imipenem resistant A. baumannii was rarely encountered. Antimicrobial resistance was common in nontyphoid Salmonella, S. choleraesuis and serogroup B isolates in particular. CONCLUSION: The high rates of antimicrobial resistance among these major bacterial pathogens in this new hospital are impressive and alarming. Judicious use of antimicrobial agents can never be overemphasized. Continued surveillance of the changes of resistance patterns over time is necessary.

Drug Resistance, Bacterial↗

PubMed2025

Macrolide-resistant Mycoplasma pneumoniae resurgence in Chinese children in 2023: a longitudinal, cross-sectional, genomic epidemiology study.

BACKGROUND: After a prolonged period of low detection rates, Mycoplasma pneumoniae resurged in China, during September to November, 2023, raising global concern. This study aims to gain a better understanding of the genetic mechanisms underlying the 2023 increase in cases and the evolutionary dynamics of the epidemic populations, which has been previously hampered due to limited genomic data of this pathogen. METHODS: We sequenced 685 M pneumoniae isolates, including 248 isolates from 11 Chinese provinces and municipalities in 2023 and 437 isolates from Beijing (2013-22). By analysing these isolates and 436 publicly global sequences, we reconstructed the pathogen's evolutionary history using time-calibrated phylogenies and effective population size inference. We investigated potential genomic variations contributing to the 2023 resurgence through genome-wide association study and conducted phylogeographic analysis of the 2023 isolates across China. FINDINGS: Two macrolide-resistant epidemic clusters (T1-2-EC1 and T2-2-EC2) were responsible for the 2023 resurgence in China. Both clusters, having acquired the 23S ribosomal RNA A2063G mutation conferring macrolide resistance, emerged in approximately 1997 and 2014, respectively, and subsequently outcompeted their predecessor populations. This coincided with China's large-scale adoption of azithromycin for paediatric community-acquired pneumonia around the early 2000s. Aside from macrolide resistance, T1-2-EC1 independently acquired 17 clade-specific mutations and T2-2-EC2 four clade-specific mutations, which could further explain their increased competitiveness. Whole-genome analysis revealed no resurgence-specific mutations in the 2023 isolates. Phylogeographic analysis showed rapid mixing of T1-2-EC1 isolates between different sampled regions within China. INTERPRETATION: Our study provides evidence that the 2023 resurgence in China is a continuation of the pre-COVID epidemic, rather than emergence of novel variants. The high prevalence of macrolide resistance and rapid intranational spread emphasise the urgent need for enhanced global surveillance of this pathogen. FUNDING: National Key Research and Development Program of China, National Natural Science Foundation of China for Key Programs of China Grants, and Beijing High-Level Public Health Technical Talent Project.

Humans↗

PubMed1993

A population-based assessment of invasive disease due to group B Streptococcus in nonpregnant adults.

BACKGROUND: Group B streptococci (Streptococcus agalactiae) are a major cause of meningitis and septicemia in neonates and pregnant women, but the importance of group B streptococcal disease in nonpregnant adults has not been clearly defined. METHODS: We conducted a prospective surveillance of the pathogens responsible for meningitis for a period of 24 months in 35 hospitals and a referral laboratory in metropolitan Atlanta. We reviewed the clinical and laboratory records of all the nonpregnant adults identified as having invasive group B streptococcal disease during this period. RESULTS: During 1989 and 1990 there were 424 patients with invasive group B streptococcal disease (annual incidence, 9.2 cases per 100,000 population). Of these patients, 46 percent were 1 month of age or younger, 6 percent were older than 1 month but younger than 18 years of age, and 48 percent were 18 or older. Men and nonpregnant women accounted for 68 percent (n = 140) of all cases among adults (annual incidence, 4.4 per 100,000). Clinical and laboratory records were available for 137. In the nonpregnant adult patients (age, 18 to 99 years), the most common clinical diagnoses were skin, soft-tissue, or bone infection (in 36 percent); bacteremia with no identified source (30 percent); urosepsis (14 percent); pneumonia (9 percent); and peritonitis (7 percent). Risk factors included older age (> or = 60 years), the presence of diabetes mellitus, the presence of malignant neoplasms, and infection with the human immunodeficiency virus. The mortality rate in nonpregnant adults was 21 percent, accounting for 67 percent of all deaths related to group B streptococcal infection during the surveillance period. CONCLUSIONS: Invasive group B streptococcal infection is a major problem not only in pregnant women and neonates but also in nonpregnant adults, especially those who are elderly and those who have chronic diseases.

AIDS-Related Opportunistic Infections↗

PubMed2002

BMS284756 (formerly T-3811, a des-fluoroquinolone) potency and spectrum tested against over 10,000 bacterial bloodstream infection isolates from the SENTRY antimicrobial surveillance programme (2000).

BMS284756 is a novel des-F (6)-quinolone, which has a wide range of activity against many species of Gram-positive and -negative organisms. The potency of BMS284756 was compared with that of other quinolones, including ciprofloxacin, gatifloxacin and levofloxacin, and was tested against >10,000 bloodstream isolates from the year 2000 SENTRY antimicrobial surveillance programme. Twelve pathogens accounted for nearly all of the referred isolates and included Staphylococcus aureus, coagulase-negative staphylococci, Escherichia coli, Klebsiella pneumoniae, Enterobacter spp., Serratia spp., Pseudomonas aeruginosa, Acinetobacter spp., Enterococcus spp., Streptococcus pneumoniae and beta-haemolytic or viridans group streptococci. Of the four quinolones tested, BMS284756 was the most active overall against Staphylococcus spp. (MIC(50) < or = 0.03 mg/L) and Streptococcus spp. (MIC(50) 0.06 mg/L). In contrast, BMS284756 was less potent than the other quinolones against the enteric Gram-negative bacilli (MIC(50) < or = 0.03-1 mg/L). With a proposed breakpoint of < or =4 mg/L, BMS284756 may be a therapeutic alternative pending the results of clinical trials.

Anti-Infective Agents↗

PubMed2005

Geographical and ecological analysis of resistance, coresistance, and coupled resistance to antimicrobials in respiratory pathogenic bacteria in Spain.

A multicenter susceptibility surveillance (the S.A.U.C.E. project) including 2,721 Streptococcus pneumoniae, 3,174 Streptococcus pyogenes, and 2,645 Haemophilus influenzae consecutive isolates was carried out in 25 hospitals all over Spain from November 2001 to October 2002 to evaluate the current epidemiology of resistance of the main bacteria involved in community-acquired respiratory tract infections. Susceptibility testing was performed in a single centralized laboratory by a broth microdilution method. The prevalence of resistant S. pneumoniae strains was 0.4% for cefotaxime, 4.4% for amoxicillin and amoxicillin-clavulanic acid, 25.6% for cefuroxime-axetil, 34.5% for erythromycin, clarithromycin, and azithromycin, and 36.0% for cefaclor. Phenotypes of resistance to erythromycin were MLS(B) (macrolide-lincosamide-streptogramin B) in 89.9% (gene ermB) and M (macrolide) in 9.7% of cases (gene mefA). No strain harbored both genes simultaneously. Serotypes 19, 6, 23, 14, and 3 were the most prevalent, accounting for 54.6% of the total isolates. Resistance to macrolides seems to be the most alarming point, since among penicillin-susceptible isolates it reached 15.1% compared to 55.8% among penicillin-resistant strains. Geographically, a number of regions had rates of erythromycin resistance above 40% (even higher in children). Resistance to erythromycin was also high in S. pyogenes isolates: mean regional 33.2%, beta-lactamase-producing H. influenzae were 20%, whereas 4.4% had a beta-lactamase-negative, ampicillin-resistant phenotype. We highlight the importance of different geographical frequencies of coresistance (associations of resistance to different drugs within the same species) and coupled resistance (association of resistance between different species) probably resulting from different local coselective events.

Anti-Infective Agents↗

PubMed2006

Development and validation of a PulseNet standardized pulsed-field gel electrophoresis protocol for subtyping of Vibrio cholerae.

PulseNet is a network that utilizes standardized pulsed-field gel electrophoresis (PFGE) protocols with the purpose of conducting laboratory-based surveillance of foodborne pathogens. PulseNet standardized PFGE protocols are subject to rigorous testing during the developmental phase and careful evaluation during a validation process assessing its robustness and reproducibility in different laboratories. Here we describe the development and validation of a rapid PFGE protocol for subtyping Vibrio cholerae for use in PulseNet International activities. While the protocol was derived from the existing PulseNet protocol for Escherichia coli O157, various aspects of this protocol were optimized for use with V. cholerae, most notably a change of the primary and secondary restriction enzyme to SfiI and NotI, respectively, and the use of a two-block electrophoresis program. External validation of this protocol was undertaken through a collaboration between three PulseNet Asia Pacific laboratories (Public Health Laboratory Centre, Hong Kong, National Institute of Infectious Diseases, Japan, and International Center for Diarrhoeal Diseases Research-Bangladesh) and PulseNet USA. Comparison of PFGE patterns generated by each of the participating laboratories demonstrated that the protocol is robust and reproducible.

Bangladesh↗

PubMed2005

Dissemination and diversity of metallo-beta-lactamases in Latin America: report from the SENTRY Antimicrobial Surveillance Program.

Carbapenem resistance among Pseudomonas aeruginosa and Acinetobacter spp. is becoming a critical therapeutic problem worldwide. The SENTRY Antimicrobial Surveillance Program monitors pathogen frequency and antimicrobial resistance patterns of nosocomial and community-acquired infections through sentinel hospitals on five continents. Pseudomonas spp. and Acinetobacter spp. strains resistant to imipenem (MIC, >/=16 mg/l), meropenem (MIC, >/=16 mg/l), and ceftazidime (MIC, >/=32 mg/l) collected from January 2001 to December 2003 were routinely screened for antimicrobial resistance genes. Resistant isolates were initially tested for metallo-beta-lactamase (MbetaL) production by phenotypic tests (disk approximation or MbetaL Etest strip) and then characterization of the MbetaL (hydrolysis assays, PCR for bla(IMP), bla(VIM), bla(SPM), gene sequencing). Eighty-nine isolates (33 Acinetobacter spp., 54 Pseudomonas aeruginosa, and 2 P. fluorescens) had positive phenotypic screening tests. Among those, 34 isolates producing MbetaL were identified, including 7 Acinetobacter spp., 25 P. aeruginosa and 2 P. fluorescens. The MbetaLs identified were IMP-1, VIM-2 and two newly described enzymes: SPM-1 and IMP-16. The greatest concentration of MbetaL strains was in Brazil, where imipenem-resistant P. aeruginosa increased significantly in the time period evaluated by the SENTRY Program. MbetaL-producing P. aeruginosa was detected in São Paulo (SPM-1) and Brasilia (SPM-1 and IMP-16), Brazil and Caracas, Venezuela (VIM-2); while MbetaL-producing Acinetobacter spp. isolates were detected in São Paulo, Brazil (IMP-1). P. fluorescens isolates producing IMP-1 and VIM-2 were detected in São Paulo, Brazil and Santiago, Chile, respectively. The emergence and dissemination of mobile MbetaL-producing isolates represent an alarming factor for increasing resistance to carbapenems in several medical centres evaluated by the SENTRY Program in Latin America.

Acinetobacter↗

PubMed2025

Development and Validation of Amplicon-Based Protocol for Sequencing of Respiratory Syncytial Virus Genome.

The most prevalent cause of severe respiratory infections in children is the human respiratory syncytial virus (RSV). The advent of next-generation sequencing (NGS) has made it possible to incorporate this technology into pathogen monitoring and surveillance. Whole-genome sequencing (WGS) of RSV has now become a relatively widely used method for tracking viral evolution. Here we report an improved high-throughput RSV-WGS assay performed directly on clinical samples that is suitable for short-read sequencing platforms. A total of 100 RSV-positive samples collected between November 2022 and March 2024 fulfilled the inclusion cycle quantification criteria and were randomly included in the validation process. The WGS protocol was designed to amplify three distinct amplicons to cover the entire RSV genome. The protocol described here can be successfully replicated in several instances (approximately 95%) in samples with a relatively low viral load, typically corresponding to cycle of quantification values of 27-32. The amplicon-based protocol produced meaningful sequencing results in terms of median depth of coverage (more than 12000×) and median of mapped reads (> 1 × 106 reads). The sequences that had passed the filters showed a coverage of at least 98% across the entire genome, with cycle quantification values of 32. Based on the obtained data resulting in an easy-to-perform protocol helpful for the molecular epidemiology surveillance of RSV.

Humans↗

PubMed1998

Surveillance for transfusion-transmitted viral infections in the United States.

Surveillance is part of a multi-faceted programme to monitor the safety of the U. S. blood supply. The Centers for Disease Control and Prevention administers several national surveillance programmes, including pathogen- and disease-specific systems (e.g. human immunodeficiency virus, hepatitis) and programmes that focus on donors and recipients of blood and plasma products (e.g. persons with haemophilia). Data collected in these systems can be used to monitor temporal and epidemiological trends, identify risk factors for infection, facilitate identification and investigation of potential outbreaks, and evaluate intervention and prevention strategies.

Blood Donors↗

PubMed2001

Natural killer cells express estrogen receptor-alpha and estrogen receptor-beta and can respond to estrogen via a non-estrogen receptor-alpha-mediated pathway.

Natural killer (NK) cells play a crucial role in host defense against pathogens and immune surveillance against cancer. Given that estrogens have been reported to suppress NK cell activity, we sought to elucidate the mechanisms by which estrogen mediates this effect. We demonstrate by immunocytochemical staining with estrogen receptor-alpha (ERalpha)- and estrogen receptor-beta (ERbeta)-specific antibodies that both ERalpha and ERbeta are expressed in murine NK cells. We also compared the ability of high doses of 17beta-estradiol ( approximately 800 pg/ml) to regulate NK cell activity in wild-type and estrogen receptor-alpha-deficient (ERalphaKO) mice. 17beta-estradiol elicited a significant decrease in NK cell activity in both wild-type and ERalphaKO mice (P < 0.001). These data suggest that ERbeta or possibly a novel receptor is involved in mediating estrogen action on NK cell activity and raise the potential for therapeutic modulation of NK cell activity with selective estrogen receptor modulators (SERMS).

Animals↗

PubMed2003

All great truths are iconoclastic: selective decontamination of the digestive tract moves from heresy to level 1 truth.

OBJECTIVE: The objective was to compare evidence of the effectiveness, costs and safety of the traditional parenteral antibiotic-only approach against that gathered from 53 randomised trials involving more than 8,500 patients and six meta-analyses on selective decontamination of the digestive tract (SDD) to control infection on the intensive care unit (ICU). PHILOSOPHY: Traditionalists believe that all infections are due to breaches of hygiene except those established in the first 2 days, and that all micro-organisms can cause death. In contrast, newer insights show that transmission via the hands of carers are responsible only for infections occurring after one week, and that only a limited range of 15 potential pathogens contribute to mortality. INTERVENTIONS TO PREVENT ICU INFECTION: The traditional approach is based on hand disinfection aiming at the prevention of transmission of all micro-organisms, to control all infections that occur after 2 days on the ICU. The second feature is the restrictive use of systemic antibiotics, only in cases of microbiologically proven infection. In contrast, SDD aims to control the three types of infection: primary, secondary endogenous and exogenous due to 15 potential pathogens. The classical SDD tetralogy comprises four components: (i) a parenteral antibiotic, cefotaxime, administered for three days to prevent primary endogenous infections typically occurring "early"; (ii) the oropharyngeal and enteral antimicrobials, polymyxin E, tobramycin and amphotericin B administered in throat and gut throughout the treatment on the ICU to prevent secondary endogenous infections tending to develop "late"; (iii) a high standard of hygiene to control transmission of potential pathogens; and (iv) surveillance samples of throat and rectum to monitor the efficacy of the treatment. ENDPOINTS: (i) Infectious morbidity; (ii) mortality; (iii) antimicrobial resistance; and (iv) costs. RESULTS: Properly designed trials on hand disinfection have never demonstrated a reduction in either pneumonia and septicaemia, or mortality. Two randomised trials using restrictive antibiotic policies failed to show a survival benefit at 28 days. In both trials the proportion of resistant isolates obtained from the lower ways was >60% despite significantly less use of antibiotics in the test group. A formal cost effectiveness analysis of the traditional antibiotic policies has not been performed. On the other hand, two meta-analyses have shown that SDD reduces the odds ratio for lower airway infections to 0.35 (0.29-0.41) and mortality to 0.80 (0.69-0.93), with a 6% overall mortality reduction from 30% to 24%. No increase in the rate of super infections due to resistant bacteria could be demonstrated over a period of 20 years of clinical research. Four randomised trials found the cost per survivor to be substantially lower in patients receiving SDD than for those traditionally managed. CONCLUSIONS: The traditionalists still rely on level 5 evidence, i.e. expert opinion, with a grade E recommendation, whilst the proponents of SDD are able to cite level 1 evidence allowing a grade A recommendation in their attempts to control infection on the ICU. The main reason for SDD not being widely used is the primacy of opinion over evidence.

Anti-Bacterial Agents↗

PubMed2026

Identification of aviadenovirus and dependoparvovirus in an Adélie penguin fecal sample from Cape Royds (Ross Island, Antarctica).

Adenoviruses (Adenoviridae) and their associated replication-deficient dependoparvoviruses (Parvoviridae) are recognized as significant components of the avian virome. While well-studied in domestic birds, these viruses remain underexplored in wild Antarctic birds. Information is limited on viruses circulating in penguins, particularly outside of the Antarctic Peninsula Region. Here we leverage a fecal sample collected for diet analyses to identify an aviadenovirus (37,731 nt) and two distinct dependoparvoviruses. The Adélie penguin (Pygoscelis adeliae) feces-derived adenovirus exhibits a genome organization consistent with members of the genus Aviadenovirus but shares only ~64% amino acid identity in the DNA polymerase protein with its closest known relative and thus represents a new species of aviadenovirus identified in penguins. Additionally, we identified two new dependoparvoviruses, one in length of 4,869 nt and a second of 4,162 nt. These two dependoparvoviruses are diverse, sharing <61% Rep amino acid identity with those of other dependoparvoviruses. Penguin dependoparvovirus 1 represents a new species. The co-detection of these viruses in a single seasonal sample could suggest a potential helper-satellite relationship in Adélie penguins. This study provides the first evidence of aviadenoviruses in Adélie penguin feces. These findings highlight the importance of surveillance to understand pathogen dynamics in isolated Antarctic populations.

Animals↗