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PubMed1977

Aanerobic isolates in hemovac lines.

Seventeen of 68 patients (25 percent) who required the use of hemovac drainage system after major head and neck procedures had positive anaerobic islates. Co-isolation of aerobic (94 percent) and other anaerobic (29 percent) microorganisms are common. There was an increased rate of psoitive anaerobic islates with procedures requiring exposure of mucosa. Radiotherapy, except in doses greater than 6,800 rads, did not affect the culture rate. Eight of 17 patients (47 percent) with positive anaerobic isolates had infectious-related complications while five of 51 patients (10 percent) with negative cultures had similar complications. Positive anaerobic isolates in hemovac lines can be correlated with pathogens isolated from subsequent complications.

Adult↗
PubMed2001

Antibiotic therapy in intra-abdominal infections--a review on randomised clinical trials.

There have been 79 randomised antibiotic studies in intra-abdominal infections retrieved. The overall success rate of the studied antibiotics ranges from 70-100%. Unfortunately only about one fourth of the studies have used a disease severity classification, e.g., APACHE II score, despite clear recommendations by the Surgical Infections Society of North America. The mortality rate in the published antibiotic studies is still rather low (approximately 4%) and does not correspond to the average mortality in peritonitis (30-40%). Failure analysis is not uniform and only performed in about 1/5 of retrieved studies. Failure analysis included data on diagnosis, type of operation, pathogen isolated at first operation, susceptibility and persistence of pathogen, re-operation or change of antibiotic regimen, and follow-up (ICU duration, death or survival, hospitalisation). Only one study has performed an analysis of the adequacy of the surgical treatment (source control). The clinical success rate of the antibiotics studied in a larger population is comparable for gentamicin + clindamycin (80%), tobramycin + clindamycin (83%), meropenem (89%), imipenem (85%), aztreonam + clindamycin (89%), cefoxitin (88%), cefotetan (92%), moxalactam (83%), cefotaxime + metronidazole (87%), ampicillin/sulbactam (87%). Piperacillin/tazobactam has in most studies a success rate of approximately 90%. The aggregated data on adverse events and clinical failure rate do not show a major advantage for any of these antibiotics. It is striking that the adverse event rate reported for ticarcillin/clavulanic acid is low when compared to all other antibiotics, which is in contrast to severe adverse events reported for clavulanic acid. The data of quinolone studies in intra-abdominal infections do not yet allow a recommendation, even when it is acknowledged that two studies were performed with good results and a good study plan. In conclusion, the comparability of antibiotic studies in intra-abdominal infections is limited due to a lack of disease severity stratification and a relatively small study population for most antibiotics. The clinical success rate of the best-studied antibiotics is similar and the choice which antibiotic is used depends on the expected pathogens and the resistance rate in a clinical setting.

APACHE↗
PubMed2004

Evaluation of frequency of isolation and trends in antibiotic resistance among Campylobacter isolates over 11 year period.

OBJECTIVE: To analyze frequency of isolation and trends in antibiotic resistance among Campylobacter isolates over 11 year period in Microbiology Laboratory, Aga Khan University from the year 1992-2002. METHODS: Total 52,777 stool specimens were processed during the study period. Enteric pathogens isolated from 8,483 stool samples were further analyzed for frequency of isolation and antimicrobial resistance. Statistical Analysis was done by using descriptive statistics of SPSS version 10. Values were expressed as percentages, mean and rates. RESULTS: Campylobacter species were third in frequency of isolation with an isolation rate of 24.8%. C. jejuni was the predominant pathogen followed by C.coli. Isolation rate of Campylobacter was higher (45.7%) among children under 2 years of age as compared to other age groups. A steady rise in resistance among Campylobacter isolates against ampicillin; tetracycline and ofloxacin has been noted whereas resistance against erythromycin remained fairly low. CONCLUSION: The isolation of Campylobacter is higher from stool specimens of children of less than two years of age rendering Campylobacteriosis to be an important cause of gastroenteritis in pediatric population. This study also demonstrates a steady rise in antibiotic resistance in Campylobacter isolates especially against quinolones with fall in resistance against erythromycin throughout the study period.

Adolescent↗
PubMed1998

African swine fever virus NL gene is not required for virus virulence.

Previously, we described a highly conserved nonessential African swine fever virus (ASFV) right variable region gene, NL. Deletion of NL from the European pathogenic isolate E70 resulted in almost complete attenuation of the virus in domestic swine. To study gene function further, NL gene deletion mutants were constructed from two pathogenic African ASFV isolates, Malawi Lil-20/1 (Mal) and Pretoriuskop/96/4 (Pr4). Unexpectedly, both Mal (Mal-deltaNL) and PR4 (Pr4deltaNL) null mutants remained highly virulent when inoculated in swine. Mal-deltaNL exhibited a disease and virulence phenotype indistinguishable from its revertant, Mal-NLR, which caused 100% mortality. Mortality among Pr4deltaNL-infected animals was also high; however, a significant delay in onset of fever and viraemia and in time to death was observed. These data indicate that NL gene function is not required for ASFV virulence and that other yet-to-be identified viral determinants perform significant virulence functions in these African field isolates.

African Swine Fever Virus↗
PubMed1994

A 4-year survey of antimicrobial susceptibility trends for isolates from cattle with bovine respiratory disease in North America.

The antimicrobial susceptibility trends of bovine respiratory disease (BRD) pathogens isolated from 1988 to 1992 were determined. A total of 880 isolates representing Pasteurella haemolytica, Pasteurella multocida, and Haemophilus somnus were used in the study. Overall, resistance to ampicillin, tetracycline, erythromycin, and sulfamethazine was frequently encountered among strains of P. haemolytica and P. multocida. Ceftiofur, an extended-spectrum cephalosporin originally marketed in 1988 for the treatment of BRD, was very active against the BRD pathogens tested; the MIC of ceftiofur for 90% of isolates tested was < or = 0.06 microgram/ml. Resistance to spectinomycin varied on the basis of the breakpoint used. Substantial variation in the year-to-year susceptibility of BRD pathogens to tilmicosin, a new macrolide antimicrobial agent, was observed. The proportion of susceptible P. haemolytica isolates ranged from 84.7% in the second year to 7.1% in the third year and 78.2% in the fourth year. Similar fluctuations were observed with strains of P. multocida.

Animals↗
PubMed1985

Treatment of infections in hospitalized patients with ticarcillin plus clavulanic acid. A comparative study.

Ninety patients at the Wilmington Medical Center were enrolled in a comparative study to evaluate the efficacy and toxicity of ticarcillin plus clavulanic acid in the treatment of a variety of infections. Forty-seven women with obstetric or gynecologic infections were randomly assigned to receive ticarcillin plus clavulanic acid or cefoxitin. Forty-three patients with gram-negative septicemia or lower respiratory tract infection were given ticarcillin plus clavulanic acid or tobramycin plus piperacillin in a randomized fashion. Of the 47 women with obstetric or gynecologic infections, 23 were randomly assigned to receive ticarcillin plus clavulanic acid, and 24 were randomly assigned to receive cefoxitin. Several patients in each group had underlying diseases such as diabetes, obesity, and hypertension. Of the 27 pathogens isolated in the group receiving ticarcillin plus clavulanic acid, 26 (96 percent) were eradicated, including all three ticarcillin-resistant pathogens. In the cefoxitin-treated group, 31 of the 33 (94 percent) pathogens were eliminated, including all four ticarcillin-resistant organisms. Three reinfections or superinfections occurred, and cefoxitin therapy failed to eliminate an enterococcus isolate from the endometrium in one patient. The clinical response in both treatment groups was excellent. Either cure or clinical improvement was achieved for all 18 sites of infection in the ticarcillin plus clavulanic acid-treated group and for all 22 sites in the cefoxitin-treated group. There were no systemic drug reactions in either treatment group. In one patient in the cefoxitin-treated group, local phlebitis developed at the infusion site. This reaction responded to local therapy. There were no local reactions among the patients receiving ticarcillin plus clavulanic acid. Of the 43 patients with gram-negative septicemia or lower respiratory tract infection, 21 were randomly assigned to receive ticarcillin plus clavulanic acid and 22 were assigned to receive tobramycin plus piperacillin. Thirty-six patients had gram-negative sepsis, and seven patients had lower respiratory tract infection. Nine of the 36 patients suspected of having gram-negative sepsis were not evaluable because no pathogen was isolated prior to treatment. Twenty-two of the 27 patients treated for septicemia had good clinical and microbiologic responses. Three of the seven patients with pneumonia were not evaluable. Of the four evaluable patients, two had pneumococcus pneumonia; one was treated with tobramycin plus piperacillin and one with ticarcillin plus clavulanic acid. In both instances, the clinical and bacteriologic responses were considered good.

Adolescent↗
PubMed2005

Integrative genomic, transcriptional, and proteomic diversity in natural isolates of the human pathogen Burkholderia pseudomallei.

Natural isolates of pathogenic bacteria can exhibit a broad range of phenotypic traits. To investigate the molecular mechanisms contributing to such phenotypic variability, we compared the genomes, transcriptomes, and proteomes of two natural isolates of the gram-negative bacterium Burkholderia pseudomallei, the causative agent of the human disease melioidosis. Significant intrinsic genomic, transcriptional, and proteomic variations were observed between the two strains involving genes of diverse functions. We identified 16 strain-specific regions in the B. pseudomallei K96243 reference genome, and for eight regions their differential presence could be ascribed to either DNA acquisition or loss. A remarkable 43% of the transcriptional differences between the strains could be attributed to genes that were differentially present between K96243 and Bp15682, demonstrating the importance of lateral gene transfer or gene loss events in contributing to pathogen diversity at the gene expression level. Proteins expressed in a strain-specific manner were similarly correlated at the gene expression level, but up to 38% of the global proteomic variation between strains comprised proteins expressed in both strains but associated with strain-specific protein isoforms. Collectively, >65 hypothetical genes were transcriptionally or proteomically expressed, supporting their bona fide biological presence. Our results provide, for the first time, an integrated framework for classifying the repertoire of natural variations existing at distinct molecular levels for an important human pathogen.

Bacterial Proteins↗
PubMed1991

[The comparison of drug susceptibility of antituberculous agents against colonizing M. intracellulare and infectious M. intracellulare].

The susceptibility of antituberculous agents against colonized M. intracellulare which were isolated from patients with pulmonary disease and infectious M. intracellulare (pathogens) isolated from atypical mycobacterial culture was investigated. Aminoglycosides were more potent against colonized organisms than against pathogens. Isoniazid, ethambutol and rifampicin showed less potent antimicrobial activity against both colonized organism and pathogens as compared to aminoglycosides. On the contrary susceptibility of cycloserine against colonized organisms was as potent as against pathogens.

Aged↗
PubMedDate not supplied

Canadian ofloxacin susceptibility study: a comparative study from 18 medical centers. Canadian Ofloxacin Study Group.

Ofloxacin, a newer fluorinated 4-quinolone having a broad spectrum of activity was evaluated against 5,553 clinical pathogens isolated from urine, respiratory tract, skin and genital tract infections at 18 Canadian Medical Centers spread across the nation. Approximately 300 strains were reported (zone diameters) from each site. The zones of ofloxacin, other fluoroquinolones, oral cephalosporins and penicillins were analyzed and interpreted by NCCLS criteria. Ofloxacin had the widest spectrum of activity against gram-positive organisms and most gram-negative organisms, while ciprofloxacin was only superior for the Pseudomonas spp. The percentage of isolates susceptible to ofloxacin was as follows: for respiratory tract pathogens = 94%, for skin and soft tissue infections = 94%, for urinary tract organisms = 93% and for genital tract isolates = 94%.

Anti-Bacterial Agents↗
PubMed1990

Susceptibility of laboratory rats to isolates of Borrelia burgdorferi from different geographic areas.

One week old LEW/N rats were inoculated with 15 different isolates of Borrelia burgdorferi from 3 major North American (Northeast, Midwest, and Pacific) and 1 European endemic areas. At 30 days after inoculation, several tissues were cultured for B. burgdorferi and examined for histopathological changes. Sera were tested for IgM and IgG antibody to B. burgdorferi by an enzyme-linked immunosorbent assay. One or more isolates from each geographic region was recovered by culture and caused arthritis in the rats. No differences in pattern or severity of disease were apparent among pathogenic isolates. Several recovered isolates failed to infect rats, or did not cause disease. Rats that were actively infected seroconverted but uninfected rats did not. Infectivity and pathogenicity of B. burgdorferi isolates could not be correlated with molecular weights or expression of outer surface proteins based on agar gel electrophoresis.

Animals↗
PubMed2006

cDNA microarray analysis of differential gene expression and regulation in clinically drug-resistant isolates of Candida albicans from bone marrow transplanted patients.

Fungi have emerged as the fourth most common pathogens isolated in nosocomial bloodstream infections, and Candida albicans is the most common human fungal pathogen. Only a few antibiotics are effective in the treatment of fungal infections. In addition, the repetition and lengthy duration of fluconazole therapy has led to an increased incidence of azole resistance and treatment failure associated with C. albicans. To investigate the mechanism of drug resistance and explore new targets to treat clinically resistant fungal pathogens, we examined the large-scale gene expression profile of two sets of matched fluconazole-susceptible and -resistant bloodstream C. albicans isolates from bone marrow transplanted (BMT) patients for the first time by microarray analysis. More than 198 differentially expressed genes were identified and they were confirmed and validated by RT-PCR independently. Not surprisingly, the resistant phenotype is associated with increased expression of CDR mRNA, as well as some common genes involved in drug resistance such as CaIFU5, CaRTA2 and CaIFD6. Meanwhile, some special functional groups of genes, including ATP binding cassette (ABC) transporter genes (IPF7530, CaYOR1, CaPXA1), oxidative stress response genes (CaALD5, CaGRP1, CaSOD2, IPF10565), copper transport and iron mobilization-related genes (CaCRD1/2, CaCTR1/2, CaCCC2, CaFET3) were found to be differentially expressed in the resistant isolates. Furthermore, among these differentially expressed genes, some co-regulated with CaCDR1, CaCDR2 and CaIFU5, such as CaPDR16 and CaIFD6, have a DRE-like element and may interact with TAC1 in the promoter region. These findings may shed light on mechanisms of azole resistance in C. albicans and clinical antifungal therapy.

ATP-Binding Cassette Transporters↗
PubMed2006

Antimicrobial activity of a novel peptide deformylase inhibitor, LBM415, tested against respiratory tract and cutaneous infection pathogens: a global surveillance report (2003-2004).

OBJECTIVES: To evaluate the spectrum of activity and potency of LBM415, the first of the peptide deformylase inhibitor (PDFI) class to be developed for treatment of community-acquired respiratory tract infections and uncomplicated skin and soft tissue infections (uSSTI), against a large, contemporary international collection of targeted pathogens collected during 2003-2004. METHODS: A total of 21,636 isolates were tested by reference broth microdilution methods as part of a longitudinal international antimicrobial resistance surveillance study. Characteristics of the organism collection included resistance to oxacillin among 35.0% of Staphylococcus aureus and 76.0% of coagulase-negative staphylococci (CoNS); resistance to penicillin (MIC > or = 2 mg/L) among 18.0% of Streptococcus pneumoniae; vancomycin resistance among 20.0% of Enterococcus spp. and ampicillin resistance among 22.0% of Haemophilus influenzae. RESULTS: LBM415 displayed potent activity against staphylococci, streptococci, Enterococcus faecium and Moraxella catarrhalis, with > or = 99.0% of strains being inhibited at < or = 4 mg/L; 97.0% of Enterococcus faecalis isolates and 92.0% of H. influenzae isolates were also inhibited at this concentration. Seventy-seven percent of Burkholderia cepacia and 82.0% of Stenotrophomonas maltophilia were inhibited at < or = 8 mg/L. No differences in LBM415 activity against S. aureus, CoNS, S. pneumoniae, Enterococcus spp. and H. influenzae were detected for subsets susceptible or resistant to antimicrobials such as oxacillin, penicillin, ampicillin, macrolides, vancomycin and fluoroquinolones. While regional differences were apparent with some comparator agents, sensitivity to LBM415 did not vary significantly among strains from the various geographic areas sampled. One isolate of S. aureus displayed high-level resistance to LBM415 owing to multiple sequence changes in resistance phenotype genes (defB and fmt), despite the absence of the compound in clinical practice. This isolate remained susceptible to all other antimicrobials tested except for penicillin. CONCLUSIONS: With few differences detected among strains from various geographic regions, the first PDFI class agent to enter clinical development has consistently demonstrated a broad spectrum of activity against commonly isolated pathogens associated with uncomplicated respiratory and cutaneous infections. These compounds represent a significant therapeutic advance owing to their novel mechanism of action and antibacterial spectrum, including activity against resistant organisms, should pharmacokinetic and pharmacodynamic parameters support their continued development. Given the detection of a pre-existing PDFI-resistant isolate of S. aureus as demonstrated here, surveillance for resistance among the PDFI-targeted pathogens following introduction of this class of agent into clinical usage will be an important component of future studies.

Amidohydrolases↗
PubMed2003

[Acute pyelonephritis: bacteriological data and general course of germ resistance].

Recent bacteriological data concerning pyelonephritis mainly focus on sensitivity to antibiotics and virulence factors. Epidemiologically, and regardless of age and sex of the patients, E. coli remains the most often isolated pathogen. Only 55% of E. coli strains (43% if isolated during a nosocomial infection) are sensitive to amoxicillin. Resistance to parenterally administered third generation cephalosporins remain exceptional. Fluoroquinolones remain very active, particularly in community-acquired infections (>95% sensitive strains). P. aeruginosa, S. aureus and enterococci are mainly isolated during nosocomial infections or in patients with a history of previous hospital admissions. Adhesion factors to urothelial cells are of uppermost importance in the pathogenesis of urinary infection. Adhesins G borne by fimbriae P are mainly concerned. Also, hemolysin is very often present in strains responsible for pyelonephritis. As to the search for these factors in the diagnosis of pyelonephritis, particularly in children, further studies are needed. The choice of antibiotherapy not only rests upon antibiogram data, but also upon pharmacological characteristics of the antibiotic.

Acute Disease↗
PubMed1997

Isolation.

Patients infected or colonized with certain microorganisms must be placed in isolation while hospitalized to prevent nosocomial transmission of these pathogens. Isolation systems enable healthcare workers to identify patients who need to be isolated and to institute the appropriate precautions. This article presents an overview of isolation precautions, emphasizing the latest guidelines from the Centers for Disease Control and Prevention.

Centers for Disease Control and Prevention, U.S.↗
PubMed1996

Once-daily, 3-day azithromycin versus a three-times-daily, 10-day course of co-amoxiclav in the treatment of adults with lower respiratory tract infections: results of a randomized, double-blind comparative study.

A 3-day regimen of azithromycin (500 mg once daily) and a 10-day regimen of co-amoxiclav (625 mg three times daily) were compared in a double-blind study of 67 patients with acute infectious exacerbations of chronic bronchitis (AIECBs, n = 54), acute bronchitis (n = 7), or pneumonia (n = 6). In patients treated with azithromycin, satisfactory clinical responses (cure or improvement) were seen in 24/28 (86%) patients with AIECBs, 2/4 (50%) with acute bronchitis and 2/2 (100%) with pneumonia. Responses were satisfactory in 24/26 (92%), 4/4 (100%) and 4/4 (100%) patients, respectively, receiving co-amoxiclav. Streptococcus pneumoniae and Haemophilus influenzae were the commonest pathogens isolated at baseline. At the end of treatment, baseline pathogens were eradicated in 9/10 microbiologically-assessable patients treated with azithromycin and in 10/10 treated with co-amoxiclav. Adverse events related or possibly related to treatment occurred in five patients in each treatment group; the majority of these events affected the gastrointestinal system. One patient in each treatment group discontinued therapy because of adverse events. The study, therefore, demonstrates that 500 mg azithromycin administered once daily for 3 days is as efficacious and well tolerated as co-amoxiclav given three times daily for 10 days in the domiciliary treatment of adults with acute lower respiratory tract infections.

Adolescent↗
PubMed2005

Arabidopsis SENESCENCE-ASSOCIATED GENE101 stabilizes and signals within an ENHANCED DISEASE SUSCEPTIBILITY1 complex in plant innate immunity.

Plant innate immunity against invasive biotrophic pathogens depends on the intracellular defense regulator ENHANCED DISEASE SUSCEPTIBILITY1 (EDS1). We show here that Arabidopsis thaliana EDS1 interacts in vivo with another protein, SENESCENCE-ASSOCIATED GENE101 (SAG101), discovered through a proteomic approach to identify new EDS1 pathway components. Together with PHYTOALEXIN-DEFICIENT4 (PAD4), a known EDS1 interactor, SAG101 contributes intrinsic and indispensable signaling activity to EDS1-dependent resistance. The combined activities of SAG101 and PAD4 are necessary for programmed cell death triggered by the Toll-Interleukin-1 Receptor type of nucleotide binding/leucine-rich repeat immune receptor in response to avirulent pathogen isolates and in restricting the growth of normally virulent pathogens. We further demonstrate by a combination of cell fractionation, coimmunoprecipitation, and fluorescence resonance energy transfer experiments the existence of an EDS1-SAG101 complex inside the nucleus that is molecularly and spatially distinct from EDS1-PAD4 associations in the nucleus and cytoplasm. By contrast, EDS1 homomeric interactions were detected in the cytoplasm but not inside the nucleus. These data, combined with evidence for coregulation between individual EDS1 complexes, suggest that dynamic interactions of EDS1 and its signaling partners in multiple cell compartments are important for plant defense signal relay.

Amino Acid Sequence↗
PubMed1996

Aetiology of acute diarrhoea in hospitalized children in Hong Kong.

To determine the role of enteric pathogens in acute childhood diarrhoea in Hong Kong, 388 children with diarrhoea and 306 children of similar age without diarrhoea were evaluated in a hospital-based study during a one-year period from August 1994 to July 1995. Of the diarrhoeal cases, 55% were under 1 year and 95% were below 5 years of age. On admission, 22% had some dehydration but none was severely dehydrated. All children were well nourished. Oyer 60% of children with diarrhoea had one or more pathogens in their stool. Rotavirus was the most commonly isolated pathogen (34.6%), followed by Salmonella (23.3%), Campylobacter (4.7%) and Shigella (2.1%). Rotavirus was not assessed in the controls and was detected mainly during the winter months December to February. Bacterial pathogens were identified more commonly in diarrhoea patients (30%) than in controls (5.6%) (P < 0.001). Despite rapid recent socioeconomic development in Hong Kong, non-typhoidal Salmonella diarrhoea remains a significant local problem in infants under 1 year. Further detailed assessment of the transmission and prevention of this infection is required.

Acute Disease↗