The Surgical Infection Society revised guidelines on the management of intra-abdominal infection

Background: Previous evidence-based guidelines on the management of intra-abdominal infection (IAI) were published by the Surgical Infection Society (SIS) in 1992, 2002, and 2010. At the time the most recent guideline was released, the plan was to update the guideline every five years to ensure the timeliness and appropriateness of the recommendations. Methods: Based on the previous guidelines, the task force outlined a number of topics related to the treatment of patients with IAI and then developed key questions on these various topics. All questions were approached using general and specific literature searches, focusing on articles and other information published since 2008. These publications and additional materials published before 2008 were reviewed by the task force as a whole or by individual subgroups as to relevance to individual questions. Recommendations were developed by a process of iterative consensus, with all task force members voting to accept or reject each recommendation. Grading was based on the GRADE (Grades of Recommendation Assessment, Development, and Evaluation) system; the quality of the evidence was graded as high, moderate, or weak, and the strength of the recommendation was graded as strong or weak. Review of the document was performed by members of the SIS who were not on the task force. After responses were made to all critiques, the document was approved as an official guideline of the SIS by the Executive Council. Results: This guideline summarizes the current recommendations developed by the task force on the treatment of patients who have IAI. Evidence-based recommendations have been made regarding risk assessment in individual patients; source control; the timing, selection, and duration of antimicrobial therapy; and suggested approaches to patients who fail initial therapy. Additional recommendations related to the treatment of pediatric patients with IAI have been included. Summary: The current recommendations of the SIS regarding the treatment of patients with IAI are provided in this guideline

Para-cresol production by Clostridium difficile affects microbial diversity and membrane integrity of Gram-negative bacteria

Clostridium difficile is a Gram-positive spore-forming anaerobe and a major cause of antibiotic-associated diarrhoea. Disruption of the commensal microbiota, such as through treatment with broad-spectrum antibiotics, is a critical precursor for colonisation by C. difficile and subsequent disease. Furthermore, failure of the gut microbiota to recover colonisation resistance can result in recurrence of infection. An unusual characteristic of C. difficile among gut bacteria is its ability to produce the bacteriostatic compound para-cresol (p-cresol) through fermentation of tyrosine. Here, we demonstrate that the ability of C. difficile to produce p-cresol in vitro provides a competitive advantage over gut bacteria including Escherichia coli, Klebsiella oxytoca and Bacteroides thetaiotaomicron. Metabolic profiling of competitive co-cultures revealed that acetate, alanine, butyrate, isobutyrate, p-cresol and p-hydroxyphenylacetate were the main metabolites responsible for differentiating the parent strain C. difficile (630Δerm) from a defined mutant deficient in p-cresol production. Moreover, we show that the p-cresol mutant displays a fitness defect in a mouse relapse model of C. difficile infection (CDI). Analysis of the microbiome from this mouse model of CDI demonstrates that colonisation by the p-cresol mutant results in a distinctly altered intestinal microbiota, and metabolic profile, with a greater representation of Gammaproteobacteria, including the Pseudomonales and Enterobacteriales. We demonstrate that Gammaproteobacteria are susceptible to exogenous p-cresol in vitro and that there is a clear divide between bacterial Phyla and their susceptibility to p-cresol. In general, Gram-negative species were relatively sensitive to p-cresol, whereas Gram-positive species were more tolerant. This study demonstrates that production of p-cresol by C. difficile has an effect on the viability of intestinal bacteria as well as the major metabolites produced in vitro. These observations are upheld in a mouse model of CDI, in which p-cresol production affects the biodiversity of gut microbiota and faecal metabolite profiles, suggesting that p-cresol production contributes to C. difficile survival and pathogenesis.Peer reviewedFinal Published versio

ANTIBACTERIAL ACTIVITY OF CEFOPERAZONE AGAINST N.GONORRHOEAE STRAINST

1) 1981年8月より1982年4月までに都立台東病院で臨床分離された淋菌53株に対するcefoperazoneおよびpenicillin G, ampicillin, tetracycline, kanamycin, spectinomycinの抗菌力について検討した.2) Penicillin Gおよびampicillinでは, MIC 0.8 μg/ml以上の耐性淋菌は約60%であり, MIC 25-100 μg/ml以上を示すβ-lactamase産生淋菌も5株(9%)認められた.Tetracyclineでは耐性株は約50%で, kanamycinおよびspectinomycinでは耐性株はほとんどみられなかった.3) CefoperazoneのMICは, ≦0.0125-0.8 μg/mlの低い値に分布し, MICのピークは0.2 μg/mlにあった.Cefoperazoneは, 他の5薬剤との間に感受性相関は認められず, penicillin耐性淋菌にもtetracycline耐性淋菌にも, 強い抗菌力を示していたThe in vitro action of cefoperazone, penicillin G, ampicillin, tetracycline, kanamycin and spectinomycin was tested against 53 gonococcal strains of clinical isolates obtained from patients at our Hospital between August, 1981 and April, 1982. In this study, about 60% of the strains tested were resistant to penicillin G and ampicillin with MIGs of greater than 0.8 µg/ml for these drugs. There were 5 (9 %) β-Iactamase producing gonococcal strains with MIGs of 25-<100 µg/ml for penicillin G and ampicillin. Although about 50% of the strains tested were resistant to tetracycline, there were few strains resistant to kanamycin and spectinomycin. The MIG range for cefoperazone was low-MIG: ≦0.0125-0.8 µg/ml, and the peak MIG was 0.2 µg/ml. Gefoperazone did not show cross resistance with the other 5 drugs tested. Gefoperazone showed high antibacterial activity against both penicillin resistant and tetracycline resistant gonococcal strains

Antibacterial properties of imipenem with special reference to the activity against methicillin-resistant staphylococci, cefotaxime-resistant Enterobacteriaceae and Pseudomonas aeruginosa

Imipenem was examined with standardized agar dilution procedures against a wide range of bacteria. Geometric mean MICs against the genera Escherichia, Klebsiella, Enterobacter, Citrobacter and Serratia were 0·1-0·4 mg/1, and Proteus and Providencia spp. were inhibited by 0·25-4 mg/1. Acinetobacter calcoaceticus var. anitratum strains were inhibited by concentrations ranging from 0·12-0·5 mg/1. Methicillin-susceptible staphylococci were highly susceptible to the drug (MICs: ⩾0·03 mg/1) and enterococci were inhibited by 0·25-16 mg/1. Most of the multi-resistant JK corynebacteria were resistant to imipenem. Imipenem was more active than any other ß-lactam against methicillin-resistant staphylococci; this was also demonstrated in a population analysis. Imipenem-resistant minorities in populations, however, were also observed. Cefotaxime-resistant and -intermediate Enterobacter and Citrobacter strains were inhibited by concentrations of 0·5 mg/1 or less. No third-generation cephalosporin nor any other ß-lactam showed similarly high activity against these groups of organisms. Among 20 ceftazidime-resistant and 20 ceftazidime-susceptible isolates of Pseudomonas aeruginosa, no strain was resistant and only five ceftazidime-resistant strains were intermediately susceptible (MIC, 8 mg/1) to imipene

Identification of New Drug Candidates Against \u3cem\u3eBorrelia burgdorferi\u3c/em\u3e Using High-Throughput Screening

Lyme disease is the most common zoonotic bacterial disease in North America. It is estimated that .300,000 cases per annum are reported in USA alone. A total of 10%–20% of patients who have been treated with antibiotic therapy report the recrudescence of symptoms, such as muscle and joint pain, psychosocial and cognitive difficulties, and generalized fatigue. This condition is referred to as posttreatment Lyme disease syndrome. While there is no evidence for the presence of viable infectious organisms in individuals with posttreatment Lyme disease syndrome, some researchers found surviving Borrelia burgdorferi population in rodents and primates even after antibiotic treatment. Although such observations need more ratification, there is unmet need for developing the therapeutic agents that focus on removing the persisting bacterial form of B. burgdorferi in rodent and nonhuman primates. For this purpose, high-throughput screening was done using BacTiter-Glo assay for four compound libraries to identify candidates that stop the growth of B. burgdorferi in vitro. The four chemical libraries containing 4,366 compounds (80% Food and Drug Administration [FDA] approved) that were screened are Library of Pharmacologically Active Compounds (LOPAC1280), the National Institutes of Health Clinical Collection, the Microsource Spectrum, and the Biomol FDA. We subsequently identified 150 unique compounds, which inhibited .90% of B. burgdorferi growth at a concentration of ,25 µM. These 150 unique compounds comprise many safe antibiotics, chemical compounds, and also small molecules from plant sources. Of the 150 unique compounds, 101 compounds are FDA approved. We selected the top 20 FDA-approved molecules based on safety and potency and studied their minimum inhibitory concentration and minimum bactericidal concentration. The promising safe FDA-approved candidates that show low minimum inhibitory concentration and minimum bactericidal concentration values can be chosen as lead molecules for further advanced studies

Gastric LTi cells promote lymphoid follicle formation but are limited by IRAK-M and do not alter microbial growth.

Lymphoid tissue inducer (LTi) cells are activated by accessory cell IL-23, and promote lymphoid tissue genesis and antibacterial peptide production by the mucosal epithelium. We investigated the role of LTi cells in the gastric mucosa in the context of microbial infection. Mice deficient in IRAK-M, a negative regulator of TLR signaling, were investigated for increased LTi cell activity, and antibody mediated LTi cell depletion was used to analyze LTi cell dependent antimicrobial activity. H. pylori infected IRAK-M deficient mice developed increased gastric IL-17 and lymphoid follicles compared to wild type mice. LTi cells were present in naive and infected mice, with increased numbers in IRAK-M deficient mice by two weeks. Helicobacter and Candida infection of LTi cell depleted rag1(-/-) mice demonstrated LTi-dependent increases in calprotectin but not RegIII proteins. However, pathogen and commensal microbiota populations remained unchanged in the presence or absence of LTi cell function. These data demonstrate LTi cells are present in the stomach and promote lymphoid follicle formation in response to infection, but are limited by IRAK-M expression. Additionally, LTi cell mediated antimicrobial peptide production at the gastric epithelium is less efficacious at protecting against microbial pathogens than has been reported for other tissues

The Emerging Role of Microbial Biofilm in Lyme Neuroborreliosis

Lyme borreliosis (LB) is the most common tick-borne disease caused by the spirochete Borrelia burgdorferi in North America and Borrelia afzelii or Borrelia garinii in Europe and Asia, respectively. The infection affects multiple organ systems, including the skin, joints, and the nervous system. Lyme neuroborreliosis (LNB) is the most dangerous manifestation of Lyme disease, occurring in 10-15% of infected individuals. During the course of the infection, bacteria migrate through the host tissues altering the coagulation and fibrinolysis pathways and the immune response, reaching the central nervous system (CNS) within 2 weeks after the bite of an infected tick. The early treatment with oral antimicrobials is effective in the majority of patients with LNB. Nevertheless, persistent forms of LNB are relatively common, despite targeted antibiotic therapy. It has been observed that the antibiotic resistance and the reoccurrence of Lyme disease are associated with biofilm-like aggregates in B. burgdorferi, B. afzelii, and B. garinii, both in vitro and in vivo, allowing Borrelia spp. to resist to adverse environmental conditions. Indeed, the increased tolerance to antibiotics described in the persisting forms of Borrelia spp., is strongly reminiscent of biofilm growing bacteria, suggesting a possible role of biofilm aggregates in the development of the different manifestations of Lyme disease including LNB

Pseudomonas aeruginosa bacteremia in patients undergoing liver transplantation: An emerging problem

In our institution, Pseudomonas aeruginosa bacteremia appeared to occur with increasing frequency in patients undergoing liver transplantation. We thus conducted a prospective study to define risk factors and outcome in these patients. Over a 19-month period 6% of liver transplants were followed by Pseudomonas bacteremia. The mean age was 46 years (range, 24 to 67 years). The interval between transplantation and onset of bacteremia was 3 to 372 days (mean, 80). The incidence of Pseudomonas bacteremia in liver transplants was three times that of other transplants (heart, lung, kidney). Ninety one percent of infections were nosocomial. Polymicrobial bacteremia occurred in 30% of episodes. The portal of entry was respiratory in 30%, abdominal in 35%, and biliary in 13%. Four patients had recurrent Pseudomonas bacteremia: liver abscess (1), biliary obstruction (2), subhepatic abscess (1). Survival at 14 days was 70%. Survival rates were significantly lower for patients with hypotension, on mechanical ventilators, and increasing severity of illness (p < 0.05). Survival was higher when bacteremia occurred within the first 30 days after transplantation compared to after 30 days. A large number (43.4%) of Pseudomonas bacteremias occurred after transplant surgery or biliary tract manipulation, while the patient was receiving a prophylactic regimen of cefotaxime and ampicillin. P. aeruginosa is an important pathogen in the liver transplant recipient; prevention may be possible for a subgroup of patients with the use of prophylactic antibiotics with activity against P. aeruginosa

In vitro and in vivo evaluation of cephalosporins for the treatment of Lyme disease.

BackgroundLyme disease accounts for &gt;90% of all vector-borne disease cases in the United States and affect ~300,000 persons annually in North America. Though traditional tetracycline antibiotic therapy is generally prescribed for Lyme disease, still 10%-20% of patients treated with current antibiotic therapy still show lingering symptoms.MethodsIn order to identify new drugs, we have evaluated four cephalosporins as a therapeutic alternative to commonly used antibiotics for the treatment of Lyme disease by using microdilution techniques like minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC). We have determined the MIC and MBC of four drugs for three Borrelia burgdorferi s.s strains namely CA8, JLB31 and NP40. The binding studies were performed using in silico analysis.ResultsThe MIC order of the four drugs tested is cefoxitin (1.25 µM/mL) &gt; cefamandole (2.5 µM/mL), &gt; cefuroxime (5 µM/mL) &gt; cefapirin (10 µM/mL). Among the drugs that are tested in this study using in vivo C3H/HeN mouse model, cefoxitin effectively kills B. burgdorferi. The in silico analysis revealed that all four cephalosporins studied binds effectively to B. burgdorferi proteins, SecA subunit penicillin-binding protein (PBP) and Outer surface protein E (OspE).ConclusionBased on the data obtained, cefoxitin has shown high efficacy killing B. burgdorferi at concentration of 1.25 µM/mL. In addition to it, cefoxitin cleared B. burgdorferi infection in C3H/HeN mice model at 20 mg/kg

Prevalence and diversity of Arcobacter spp. in poultry meat in New Zealand : a thesis presented in the partial fulfillment of the requirements for the degree of Master of Science in Veterinary Microbiology and Public Health at Massey University, Palmerston North, New Zealand

The microaerophilic bacterium Arcobacter has received increased attention in recent years as an emerging foodborne human pathogen. Although phenotypically related, arcobacters differ from campylobacters in their ability to grow aerobically and at lower temperatures. Poultry are considered a significant reservoir of this organism, with an isolation rate of up to 72% in faecal samples, and up to 100% in meat samples. To date, four species; A. butzleri, A. skirrowii, A. cryaerophilus, and A. cibarius have been isolated from poultry. The first three species have also been found to be associated with human and animal illnesses such as diarrhoea, bacteraemia, mastitis and abortions. The organisms are also found in raw meat products as well as in surface and ground water. Since most laboratories still do not use appropriate isolation techniques, the occurrence of this organism in food sources and their role in human illnesses is greatly underestimated. This is the first investigation of the prevalence of arcobacters in poultry meat in New Zealand. The aim of this study was to compare the most commonly used Arcobacter isolation methods. In addition, this study aimed to estimate the prevalence of Arcobacter spp. in retail poultry in New Zealand. Other aims include comparison of genetic diversity of Arcobacter spp. isolated from three different poultry producers, and by different methods, and estimation of overall genetic diversity of arcobacters present in New Zealand. During the period of May to October 2005, a total of 150 fresh, whole, retail poultry carcass produced by three different producers were purchased through two supermarket outlets in Palmerston North, New Zealand. Isolation of Arcobacter was done by seven different techniques. Arcobacter-like organisms were identified presumptively by phenotypic tests; temperature tolerance, aerotolerance, motility , and oxidase production. These presumptive arcobacters were confirmed by a species-specific multiplex PCR (m-PCR) either as A. butzleri, A. cryaerophilus or A. skirrowii. DNA sequencing was done for selected isolates from both species to further confirm the PCR results. The PCR positive isolates were subjected to Pulsed-Field Gel Electrophoresis (PFGE) following restriction digestion with Eagl. It was found that 55.3 % of 150 retail poultry sold in New Zealand were harbouring Arcobacter species. Two species; A. butzleri and A. cryaerophilus were detected by m-PCR which was later confirmed by sequencing. A total of 189 isolates were detected by six methods from 83 retail poultry samples. A. butzleri was the predominant species and was detected in 51.3% of the samples, whereas A. cryaerophilus was detected only in 8% of the samples. A. butzleri and A. cryaerophilus accounted for 92.6% (n=175) and 7.4% (n-14) of the isolates, respectively. A. butzleri was the only Arcobacter species present in 46.6% samples, and A. cryaerophilus only in 3.3% of the samples. Both species were detected simultaneously in 4.6% of the samples. There was a wide variation among the prevalence rate of Arcobacter spp. in retail poultry from different producers varying from 30 to 98%. There was also a wide variation among the isolation rates of different methods varying from 3.3 to 39.3%. The best isolation method was found to be Arcobacter-broth enrichment followed by passive filtration through a sterile filter of 0.45μm, onto blood-agar plates. No single isolation method detected all arcobacters. PFGE of Arcobacter isolates demonstrated the occurrence of multiple genotypes of both A. butzleri and A. cryaerophilus in the retail poultry from the same producers, and even in a single poultry. The possible explanations for the large amount of heterogeneity include multiple sources of contamination, the occurrence of multiple parent genotypes for both species in a single poultry carcass, and a high degree of genomic recombination among the progeny of historical parent genotypes. This study highlights the high prevalence of Arcobacter spp. in poultry meat in New Zealand. It also indicates prevalence of arcobacters in poultry carcass varies greatly with the choice of isolation method and none of the currently available methods are appropriate for the detection of all species of arcobacters in New Zealand. Therefore, two or more methods should be used in parallel. The level of contamination of poultry carcass may vary with the processing practices of a slaughterhouse. To eliminate or reduce arcobacters in retail poultry, maintenance of slaughter hygiene is of utmost importance. This may be achieved by regular microbiological monitoring of carcasses according to the HACCP principles. Further studies comparing the fingerprinting pattern of Arcobacter spp. isolates obtained from retails poultry with human isolates are necessary to test the hypothesis that poultry meal is an important source for Arcobacter infection in human