Antibiotics Ceftazidime Research Articles

High occurrence of extended-spectrum β-lactamase-producing Salmonella in broiler carcasses from poultry slaughterhouses in South Korea.

The emergence of antibiotic-resistant foodborne Salmonella has become a major public health problem. Consumption of undercooked poultry contaminated with Salmonella can induce food poisoning in humans. In this study, we investigated the occurrence and antibiotic resistance patterns of Salmonella spp. isolated from 120 chicken carcasses produced in 6 poultry slaughterhouses in South Korea. A total of 11 samples (9.2%) were found contaminated with Salmonella: 5 isolates were serotyped as Salmonella Bellevue strain (slaughterhouse C) and 6 isolates were serotyped as Salmonella Enteritidis strain (slaughterhouse E). Salmonella Bellevue isolates were resistant to five antibiotics (ampicillin, chloramphenicol, nalidixic acid, tetracycline, and trimethoprim/sulfamethoxazole), while Salmonella Enteritidis isolates were resistant to nine antibiotics (ampicillin, cefotaxime, ceftazidime, cefazolin, cephalothin, amikacin, nalidixic acid, streptomycin, and tetracycline). All cephalosporin-resistant Salmonella Enteritidis isolates exhibited the extended-spectrum β-lactamase (ESBL) phenotype and carried the gene encoding CTX-M-15, the most prevalent ESBL enzyme worldwide. Based on molecular subtyping performed using the automated rep-polymerase chain reaction (PCR) system (DiversiLab), the isolates showing ≥ 95 similarity in their rep-PCR banding patterns were classified into 5 pulsotypes. Given that cephalosporins are the drugs of choice for invasive Salmonella infections, the high incidence of ESBL-producing strains in chicken should emphasize the necessity of regular monitoring of the occurrence of antibiotic-resistant ESBL-positive Salmonella strains in poultry meat.

Antimicrobial Efficacy of Different Solvent Extracts of Tagetes erecta L. Flower, Alone and in Combination with Antibiotics

Bacteria have evolved numerous defences against antimicrobial agent and drug resistance in pathogen is on rise. This is due to rapid development of multi-drug resistance, limited anti-bacterial spectrum and adverse effects of available anti-microbial agents. This necessitates the search for new antimicrobials with diverse structures and novel mechanism of action. Flowers are mostly used for ornamental purposes and they are not frequently worked out hence marigold flower was selected for the study. The antimicrobial activity of different solvent (Hexane, Toluene, Ethyl acetate, Acetone, Methanol and Aqueous) extracts of marigold flowers were evaluated by agar well diffusion method against a panel of pathogenic microorganisms. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of acetone extract and its fraction were evaluated. B. cereus and K. pneumonia were the most sensitive organisms to acetone extract and minimum inhibitory concentration (MIC) was 78 μg/ml. Synergistic effect of acetone extract and commercial antibiotics (chloroamphenicol and ceftazidime) against pathogenic bacteria was investigated. The best synergistic activity was with combination of acetone extract and ceftazidime against B. subtilis and P. aeruginosa with FIC indices 0.312 and 0.093 respectively. Only the polar solvent acetone extract showed promising antibacterial and synergistic activity. These results indicate that combination between plant extract and the antibiotics could be useful in fighting emerging drug-resistant microorganisms and choice of the solvent plays a prominent role in evaluating antimicrobial activity of medicinal plants. Flowers can be taken as an alternative source of antimicrobial agent against the human pathogens.

Enhancement by the artificial controlled culture for the algal treatment of antibiotic ceftazidime: a three-step response performance and high-removal efficiency

The improved activity of alga is critical for the biological enhanced treatment to remove contamination.

Frequency of PER, VEB, SHV, TEM and CTX-M Genes in Resistant Strains of Pseudomonas aeruginosa Producing Extended Spectrum β-Lactamases.

Background:Pseudomonas aeruginosa is the most common pathogen causing nosocomial infections. Resistance of P. aeruginosa strains to broad-spectrum cephalosporins may be mediated by extended-spectrum β-lactamases (ESBLs).Objectives:We intended to investigate the prevalence of ESBLs and antimicrobial susceptibilities of P. aeruginosa isolated from patients in Zahedan, Iran.Materials and Methods:In this cross-sectional study, during 2012–2013, 116 P. aeruginosa isolates were collected from a teaching hospital in Zahedan, Iran. Susceptibility to eight antimicrobial agents was carried out by disk diffusion method. The ESBL producing strains were detected by combination disk test (CDT). ESBL positive isolates as well as other isolates showing minimum inhibitory concentrations (MICs) ≥ 4 μg/mL for ceftazidime, cefotaxime, ceftriaxone and aztreonam, were screened for the presence of the genes encoding blaTEM, blaSHV, blaPER-1 and blaVEB-1, by polymerase chain reaction (PCR).Results:Ciprofloxacin and piperacillin were the most efficient antipseudomonal agents. The results disclosed that 19 (16.37%) of the isolates were multidrug resistant and 8 (6.89%) were ESBL-positive. Of the 116 isolates, 30 (25.86%) were resistant to at least one of the antibiotics ceftazidime, ceftriaxone, cefotaxime or aztreonam and among these 30 (100%), 4 (13.3%), 2 (6.6%) and 2 (6.6%), amplified blaTEM, blaVEB-1, blaPER-1 and blaSHV, respectively. From the 30 TEM-positive isolates, 22 were ESBL-negative. Sequencing of the ESBL genes verified the accuracy of the PCR products.Conclusions:According to our results, blaTEM-116 was the most frequent isolated ESBL gene among the P. aeruginosa strains isolated from patients.

Rapid detection of enterobacteriaceae producing extended spectrum beta-lactamases directly from positive blood cultures by matrix-assisted laser desorption ionization-time of flight mass spectrometry

Bacteria that produce extended-spectrum β-lactamases (ESBLs) are an increasing healthcare problem and their rapid detection is a challenge that must be overcome in order to optimize antimicrobial treatment and patient care. Matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry (MS) has been used to determine resistance to β-lactams, including carbapenems in Enterobacteriaceae, but the methodology has not been fully validated as it remains time-consuming. We aimed to assess whether MALDI-TOF can be used to detect ESBL-producing Enterobacteriaceae from positive blood culture bottles in clinical practice. In the assay, 141 blood cultures were tested, 13 of them were real bacteraemias and 128 corresponded to blood culture bottles seeded with bacterial clinical isolates. Bacteraemias were analysed by MALDI-TOF after a positive growth result and the 128 remaining blood cultures 24 h after the bacterial seeding. β-lactamase activity was determined through the profile of peaks associated with the antibiotics cefotaxime and ceftazidime and its hydrolyzed forms. Clavulanic acid was added to rule out the presence of non-ESBL mechanisms. Overall data show a 99% (103 out of 104) sensitivity in detecting ESBL in positive blood cultures. Data were obtained in 90 min (maximum 150 min). The proposed methodology has a great impact on the early detection of ESBL-producing Enterobacteriaceae from positive blood cultures, being a rapid and efficient method and allowing early administration of an appropriate antibiotic therapy.

Inhibition and destruction of Pseudomonas aeruginosa biofilms by antibiotics and antimicrobial peptides

Pseudomonas aeruginosa is one of the major nosocomial pathogen that can causes a wide variety of acute and chronic infections P. aeruginosa is a dreaded bacteria not just because of the high intrinsic and acquired antibiotic resistance rates but also the biofilm formation and production of multiple virulence factors. We investigated the in vitro activities of antibiotics (ceftazidime, tobramycin, ciprofloxacin, doripenem, piperacillin and colistin) and antimicrobial cationic peptides (AMPs; LL-37, CAMA: cecropin(1–7)-melittin A(2–9) amide, melittin, defensin and magainin-II) alone or in combination against biofilms of laboratory strain ATCC 27853 and 4 clinical strains of P. aeruginosa. The minimum inhibitory concentrations (MIC), minimum bactericidal concentration (MBC) and minimum biofilm eradication concentrations (MBEC) were determined by microbroth dilution technique. The MBEC values of antibiotics and AMPs were 80–>5120 and 640–>640mg/L, respectively. When combined with the LL-37 or CAMA at 1/10× MBEC, the MBEC values of antibiotics that active against biofilms, were decreased up to 8-fold. All of the antibiotics, and AMPs were able to inhibit the attachment of bacteria at the 1/10× MIC and biofilm formation at 1× or 1/10× MIC concentrations. Time killing curve studies showed 3-log10 killing against biofilms in 24h with almost all studied antibiotics and AMPs. Synergism were seen in most of the studied combinations especially CAMA/LL-37+ciprofloxacin against at least one or two strains’ biofilms. Since biofilms are not affected the antibiotics at therapeutic concentrations, using a combination of antimicrobial agents including AMPs, or inhibition of biofilm formation by blocking the attachment of bacteria to surfaces might be alternative methods to fight with biofilm associated infections.

Interaction of Interferon gamma-induced reactive oxygen species with ceftazidime leads to synergistic killing of intracellular Burkholderia pseudomallei.

Burkholderia pseudomallei, a facultative intracellular pathogen, causes severe infections and is inherently refractory to many antibiotics. Previous studies from our group have shown that interferon gamma (IFN-γ) interacts synergistically with the antibiotic ceftazidime to kill bacteria in infected macrophages. The present study aimed to identify the underlying mechanism of that interaction. We first showed that blocking reactive oxygen species (ROS) pathways reversed IFN-γ- and ceftazidime-mediated killing, which led to our hypothesis that IFN-γ-induced ROS interacted with ceftazidime to synergistically kill Burkholderia bacteria. Consistent with this hypothesis, we also observed that buthionine sulfoximine (BSO), another inducer of ROS, could substitute for IFN-γ to similarly potentiate the effect of ceftazidime on intracellular killing. Next, we observed that IFN-γ induced ROS-mediated killing of intracellular but not extracellular bacteria. On the other hand, ceftazidime effectively reduced extracellular bacteria but was not capable of intracellular killing when applied at 10 μg/ml. We investigated the exact role of IFN-γ-induced ROS responses on intracellular bacteria and notably observed a lack of actin polymerization associated with Burkholderia bacteria in IFN-γ-treated macrophages, which led to our finding that IFN-γ-induced ROS blocks vacuolar escape. Based on these results, we propose a model in which synergistically reduced bacterial burden is achieved primarily through separate and compartmentalized killing: intracellular killing by IFN-γ-induced ROS responses and extracellular killing by ceftazidime. Our findings suggest a means of enhancing antibiotic activity against Burkholderia bacteria through combination with drugs that induce ROS pathways or otherwise target intracellular spread and/or replication of bacteria.

Avibactam and class C β-lactamases: mechanism of inhibition, conservation of the binding pocket, and implications for resistance.

Avibactam is a novel non-β-lactam β-lactamase inhibitor that inhibits a wide range of β-lactamases. These include class A, class C, and some class D enzymes, which erode the activity of β-lactam drugs in multidrug-resistant pathogens like Pseudomonas aeruginosa and Enterobacteriaceae spp. Avibactam is currently in clinical development in combination with the β-lactam antibiotics ceftazidime, ceftaroline fosamil, and aztreonam. Avibactam has the potential to be the first β-lactamase inhibitor that might provide activity against class C-mediated resistance, which represents a growing concern in both hospital- and community-acquired infections. Avibactam has an unusual mechanism of action: it is a covalent inhibitor that acts via ring opening, but in contrast to other currently used β-lactamase inhibitors, this reaction is reversible. Here, we present a high-resolution structure of avibactam bound to a class C β-lactamase, AmpC, from P. aeruginosa that provided insight into the mechanism of both acylation and recyclization in this enzyme class and highlighted the differences observed between class A and class C inhibition. Furthermore, variants resistant to avibactam that identified the residues important for inhibition were isolated. Finally, the structural information was used to predict effective inhibition by sequence analysis and functional studies of class C β-lactamases from a large and diverse set of contemporary clinical isolates (P. aeruginosa and several Enterobacteriaceae spp.) obtained from recent infections to understand any preexisting variability in the binding pocket that might affect inhibition by avibactam.

Terpenes, Antibacterial and Modulatory Antibiotic Activity of Essential Oils from Croton hirtus L’ Hér. (Euphorbiaceae) from Ivory Coast

The chemical composition, antibacterial and modulatory antibiotic activity of essential oils isolated by hydrodistillation from the aerial parts of Croton hirtus (Euphorbiaceae) growing in Ivory Coast, were evaluated. The chemical composition was determined by gas chromatography/mass spectrometry (GC-MS). Essential oil contained 93.49 % of terpene derivatives (15.55 % and 77.94 %) monoterpenes and sesquiterpenes, respectively. Hydrocarbons monoterpenes (14.79 %) were prevalent compared to oxygenated monoterpenes (0.76 %). Moreover among sesquiterpenes, the hydrocarbons species were also detected in a higher percentage (74.06 %) than oxygenated (3.88 %). Three major components found were (E)-caryophyllene (31.75 %), germacrene-D (22.57%) and α-humulène (7.42 %). In vitro antibacterial activity was tested using diffusion disk and microdilution methods against Escherichia coli ATCC 29522 and Staphylococcus aureus ATCC 25923. It's modulatory effect combined with antibiotics gentamicin and ceftazidime was also determined. The antibacterial activity was studied by the broth microdilution method. The essential oil from Croton hirtus, were effective only against S. aureus ATCC 25922 (DD = 10.0 ± 1.0; CMI = 512 μg/mL). The MICs for gentamicin and ceftazidime, were reduced in the presence of the essential oils against S. aureus ATCC 25922, reduction of 64 to 16 μg/mL and of 16 to 8 μg/mL respectively. So, a modulatory effect of Croton hirtus essential oil combined with antibiotics was demonstrated and an important activity against bacterial S. aureus.

A broad-spectrum antibiofilm peptide enhances antibiotic action against bacterial biofilms.

Biofilm-related infections account for at least 65% of all human infections, but there are no available antimicrobials that specifically target biofilms. Their elimination by available treatments is inefficient since biofilm cells are between 10- and 1,000-fold more resistant to conventional antibiotics than planktonic cells. Here we describe the synergistic interactions, with different classes of antibiotics, of a recently characterized antibiofilm peptide, 1018, to potently prevent and eradicate bacterial biofilms formed by multidrug-resistant ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) pathogens. Combinations of peptide 1018 and the antibiotic ceftazidime, ciprofloxacin, imipenem, or tobramycin were synergistic in 50% of assessments and decreased by 2- to 64-fold the concentration of antibiotic required to treat biofilms formed by Pseudomonas aeruginosa, Escherichia coli, Acinetobacter baumannii, Klebsiella pneumoniae, Salmonella enterica, and methicillin-resistant Staphylococcus aureus. Furthermore, in flow cell biofilm studies, combinations of low, subinhibitory levels of the peptide (0.8 μg/ml) and ciprofloxacin (40 ng/ml) decreased dispersal and triggered cell death in mature P. aeruginosa biofilms. In addition, short-term treatments with the peptide in combination with ciprofloxacin prevented biofilm formation and reduced P. aeruginosa PA14 preexisting biofilms. PCR studies indicated that the peptide suppressed the expression of various antibiotic targets in biofilm cells. Thus, treatment with the peptide represents a novel strategy to potentiate antibiotic activity against biofilms formed by multidrug-resistant pathogens.

Coselection for resistance to multiple late-generation human therapeutic antibiotics encoded on tetracycline resistance plasmids captured from uncultivated stream and soil bacteria.

Transmissible plasmids captured from stream and soil bacteria conferring resistance to tetracycline in Pseudomonas were evaluated for linked resistance to antibiotics used in the treatment of human infections. Cells released from stream sediments and soils were conjugated with a rifampicin-resistant, plasmid-free Pseudomonas putida recipient and selected on tetracycline and rifampicin. Each transconjugant contained a single 50-80kb plasmid. Resistance to 11 antibiotics, in addition to tetracycline, was determined for the stream transconjugants using a modification of the Stokes disc diffusion antibiotic susceptibility assay. Nearly half of plasmids conferred resistance to six or more antibiotics. Resistance to streptomycin, gentamicin, and/or ticarcillin was conferred by a majority of the plasmids, and resistance to additional human clinical use antibiotics such as piperacillin/tazobactam, ciprofloxacin and aztreonam was observed. MICs of 16 antibiotics for representative sediment and soil transconjugants revealed large increases, relative to the Ps.putida recipient, for 11 of 16 antibiotics tested, including the expanded spectrum antibiotics cefotaxime and ceftazidime, as well as piperacillin/tazobactam, lomefloxacin and levofloxacin. Resistance to multiple antibiotics-including those typically used in clinical Pseudomonas and enterobacterial infections-can be conferred by transmissible plasmids in streams and soils. Selective pressure exerted by the use of one antibiotic, such as the common agricultural antibiotic tetracycline, may result in the persistence of linked genes conferring resistance to important human clinical antibiotics. This may impact the spread of resistance to human use antibiotics even in the absence of direct selection.

Novel Antibiotic-Eluting Gelatin-Alginate Soft Tissue Adhesives for Various Wound Closing Applications

Interest in tissue adhesives as alternatives for conventional wound closing applications such as sutures and staples has increased in the last few decades due to numerous possible advantages, including less discomfort and lower cost. In the current study, the authors developed novel tissue adhesives based on gelatin and alginate, crosslinked by carbodiimide. The antibiotic drug ceftazidime was incorporated for prevention of infection. The bonding strength of the bioadhesives, their swelling ration, drug release profile and biocompatibility were studied. The high bonding strength and good biocompatibility turns these new bioadhesives into a promising alternative for use in wound closing applications.

Antimicrobial potential of TiO2 nanoparticles against MDR Pseudomonas aeruginosa

The present study aims to evaluate the inhibition effectiveness of titanium dioxide nanoparticles in combination with cell wall active antibiotics – ceftazidime and cefotaxime against the multi-drug resistant Pseudomonas aeroginosa isolated from pus, sputum, endo-tracheal tract and broncho-alveolar lavage. Commercial Degussa-P25 TiO2 nanoparticle, antibiotics ceftazidime and cefotaxime were used in this study against multi-drug-resistant nosocomial pathogen. The nanoparticle shows antimicrobial effect on the pathogen at concentrations more than 350 μg/mL, when exposed to ultraviolet (UV) light for an hour. Minimum inhibitory concentration values obtained for the antibiotic cefotaxime were sixfolds higher than the antibiotic ceftazidime. When these antibiotics were used in combination with UV-irradiated metal nanoparticle, ceftazidime resulted in enhanced antimicrobial activity whereas cefotaxime does not show any change.

Combination Therapy of 15-Epi-Lipoxin A4 With Antibiotics Protects Mice From Escherichia coli–Induced Sepsis*

Inflammation occurs along with infection during sepsis. 15-Epi-lipoxin A4 has protective and resolving effects in experimental models of infection. In this study, we examined the effects of 15-epi-lipoxin A4 combined with antibiotics on Escherichia coli-induced peritonitis. Prospective experimental study. University research laboratory. Male C57BL/6 mice. Mice were injected with E. coli to induce peritonitis and were given either 15-epi-lipoxin A4 (1 μg/mouse) or placebo (saline) with antibiotics (ceftazidime). The effects of 15-epi-lipoxin A4 on peritoneal cell populations, bacterial burden, and cytokine production were assessed. Survival rates were observed for up to 7 days. In addition, we examined the effects of 15-epi-lipoxin A4 on peritoneal macrophages stimulated with lipopolysaccharide, CpG DNA, or live E. coli. Treatment with 15-epi-lipoxin A4 significantly reduced the number of neutrophils in the peritoneum, inhibited production of cytokines and chemokines, and decreased bacterial load in the serum. Combined treatment of 15-epi-lipoxin A4 with antibiotics significantly improved survival in E. coli-infected mice. 15-Epi-lipoxin A4 also attenuated the production of interleukin-6 and tumor necrosis factor-α by lipopolysaccharide- or CpG DNA-stimulated peritoneal macrophages. Furthermore, 15-epi-lipoxin A4 combined with antibiotics synergistically reduced the production of interleukin-6 and tumor necrosis factor-α by peritoneal macrophages stimulated with live E. coli. 15-Epi-lipoxin A4 combined with antibiotics attenuated systemic inflammation, inhibited bacteria dissemination, and improved survival in E. coli-infected mice. The reduced production of interleukin-6 and tumor necrosis factor-α by peritoneal macrophages suggested that 15-epi-lipoxin A4 blocked the initial proinflammatory response. Taken together, these data suggested that 15-epi-lipoxin A4 combined with antibiotics was beneficial in regulating the proinflammatory response in sepsis without exacerbating infection.

In Vitro Antibacterial Screening of Six Proline-Based Cyclic Dipeptides in Combination with β-Lactam Antibiotics Against Medically Important Bacteria

The in vitro synergistic antibacterial activity of six proline-based cyclic dipeptides [cyclo(D-Pro-L-Leu), cyclo(L-Pro-L-Met), cyclo(D-Pro-L-Phe), cyclo(L-Pro-L-Phe), cyclo(L-Pro-L-Tyr), and cyclo(L-Pro-D-Tyr)] in combination imipenem and ceftazidime was investigated in the present manuscript. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of the cyclic dipeptides were compared with those of the standard antibiotics (imipenem and ceftazidime). The synergistic antibacterial activities of cyclic dipeptides with imipenem or ceftazidime were assessed using the checkerboard and time-kill methods. The results of the present study showed that the combined effect of six cyclic dipeptides with imipenem predominantly recorded synergistic interaction (FIC index <0.5), whereas combination of certain cyclic dipeptides with ceftazidime recorded additive. The time-kill curve showed that the growth of the test bacteria was completely attenuated after 12-24h of treatment with a 50:50 ratio of proline-based cyclic dipeptides and antibiotics. These synergistic effects have a potential role in delaying the development of resistance as the antibacterial activity is achieved with the very low concentrations of cyclic dipeptides and antibiotics. The cytotoxicity of cyclic dipeptides was tested against VERO cell line (African green monkey kidney cell line), and no cytotoxicity was recorded for cyclic dipeptides up to 100μg/mL. These findings suggest that combination of cyclic dipeptides and antibiotics might be a good strategy for the individualization of novel templates for the development of new antimicrobial agents or combinations of drugs for antimicrobial chemotherapy. Moreover, these combinations may lead to the development of a new and vital antimicrobial combination against the infections caused by pathogenic bacteria. The in vitro synergistic activity of cyclic dipeptides with antibiotics against medically important bacteria is reported here for the first time.

Characterization of StyR-234 non-coding RNA in regulation of Multi-drug resistance in Salmonella enterica serovar typhi

Non-protein coding RNAs (npcRNA) have been recently recognized in bacterial pathogens as a new group to regulate multi-drug resistance. Among several pathogenic bacterial spcecices, Salmonella enterica serovar Typhi (S. typhi) one of the focusing target in order to prevent severe impact in human health and it pose a problem by causing high fever. we report the characterization of StyR-234, a small antisense npcRNA, discovered from Salmonella typhi. StyR-234 is located on positive strand and antisense to, bacA gene. Since bacA is known to participate in MDR, we hypothesis StyR-234 is involve in bacA regulation thus could have role in drug resistance in S. typhi. Overexperssion analysis show that S. typhi became more susceptible to six antibiotics (Amikacin, Cefepime, Trimethoprim Sulphamethoxazole, Imipenem, Meropenem, Piperacillin Tazobactam) while more resistance to two antibiotics (Ampicillin and Cefotaxime). And no changes in sensitivity for three antibiotics (Ciprofloxacin, Clindamycin and Ceftazidime). The results indicated that StyR234 increasing susceptibility to many antibiotics could be by down regulating antibiotic resistant gene bacA.

The TFPI-2 Derived Peptide EDC34 Improves Outcome of Gram-Negative Sepsis

Sepsis is characterized by a dysregulated host-pathogen response, leading to high cytokine levels, excessive coagulation and failure to eradicate invasive bacteria. Novel therapeutic strategies that address crucial pathogenetic steps during infection are urgently needed. Here, we describe novel bioactive roles and therapeutic anti-infective potential of the peptide EDC34, derived from the C-terminus of tissue factor pathway inhibitor-2 (TFPI-2). This peptide exerted direct bactericidal effects and boosted activation of the classical complement pathway including formation of antimicrobial C3a, but inhibited bacteria-induced activation of the contact system. Correspondingly, in mouse models of severe Escherichia coli and Pseudomonas aeruginosa infection, treatment with EDC34 reduced bacterial levels and lung damage. In combination with the antibiotic ceftazidime, the peptide significantly prolonged survival and reduced mortality in mice. The peptide's boosting effect on bacterial clearance paired with its inhibiting effect on excessive coagulation makes it a promising therapeutic candidate for invasive Gram-negative infections.

Prophylactic antibiotics for preventing Gram positive infections associated with long-term central venous catheters in oncology patients.

This is an updated version of the review which was first published in the Cochrane Database of Systematic Reviews in 2006. Long-term central venous catheters (CVCs), including tunnelled CVCs (TCVCs) and totally implanted devices or ports (TIDs), are increasingly used when treating oncology patients. Despite international guidelines on sterile insertion and appropriate CVC maintenance and use, infection remains a common complication. These infections are mainly caused by Gram positive bacteria. Antimicrobial prevention strategies aimed at these micro-organisms could potentially decrease the majority of CVC infections. The aim of this review was to evaluate the efficacy of antibiotics in the prevention of Gram positive infections in long-term CVCs. To determine the efficacy of administering antibiotics prior to the insertion of long-term CVCs, or flushing or locking long-term CVCs with a combined antibiotic and heparin solution, or both, to prevent Gram positive catheter-related infections in adults and children receiving treatment for cancer. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (to June 2013) and the MEDLINE and EMBASE databases (1966 to 2013). Randomised controlled trials (RCTs) comparing prophylactic antibiotics given prior to long-term CVC insertion with no antibiotics, RCTs comparing a combined antibiotic and heparin solution with a heparin-only solution to flush or lock newly inserted long-term CVCs, and RCTs comparing a combination of these interventions in adults and children receiving treatment for cancer. Two authors independently selected studies, classified them and extracted data on to a pre-designed data collection form. We pooled data using the RevMan software version 5.2 and used random-effects (RE) model methods for meta-analyses. We included 11 trials with a total of 828 oncology patients (adults and children). We assessed most included studies to be at a low or unclear risk of bias. Five trials compared the use of antibiotics (vancomycin, teicoplanin or ceftazidime) given before the insertion of the long-term CVC with no antibiotics, and six trials compared antibiotics (vancomycin, amikacin or taurolidine) and heparin with a heparin-only solution for flushing or locking the long-term CVC after use. Administering an antibiotic prior to insertion of the CVC did not significantly reduce Gram positive catheter-related sepsis (CRS) (five trials, 360 adults; risk ratio (RR) 0.72, 95% confidence interval (CI) 0.33 to 1.58; I² = 5 2%; P = 0.41).Flushing and locking long-term CVCs with a combined antibiotic and heparin solution significantly reduced the risk of Gram positive catheter-related sepsis compared with a heparin-only solution (468 participants, mostly children; RR 0.47, 95% CI 0.28 to 0.80; I² = 0%; P = 0.005). For a baseline infection rate of 15%, this reduction translated into a number needed to treat (NNT) of 12 (95% CI 9 to 33) to prevent one catheter-related infection. We considered this evidence to be of a moderate quality. There was no benefit to administering antibiotics before the insertion of long-term CVCs to prevent Gram positive catheter-related infections. Flushing or locking long-term CVCs with a combined antibiotic and heparin solution appeared to reduce Gram positive catheter-related sepsis experienced in people at risk of neutropenia through chemotherapy or disease. Due to insufficient data it was not clear whether this applied equally to TCVCs and totally implanted devices (TIDs), or equally to adults and children. The use of a combined antibiotic and heparin solution may increase microbial antibiotic resistance, therefore it should be reserved for high risk people or where baseline CVC infection rates are high (> 15%). Further research is needed to identify high risk groups most likely to benefit.

Surveillance cultures in pediatric allogeneic hematopoietic stem cell transplantation

The value of surveillance cultures in predicting systemic infections and in guiding antimicrobial treatment is controversial. We investigated 57 pediatric allo-SCTs between 2007 and 2009. ALL (34), AML (5), and severe aplastic anemia (4) were the largest patient groups. Conditioning was TBI-based in 87% and 54% developed GVHD (21% grade III-IV). Of the 2594 weekly colonization samples, 24% were positive (fecal bacteria 86%, fecal fungi 16%, Clostridium difficile 16%; throat bacteria 17% and throat fungi 4%). Enterobacteria and enterococci were the most common fecal findings, staphylococci and streptococci in the throat. Of the bacterial stool samples pretransplant, 74% (mostly enterococci) were resistant to our first-line antibiotics (ceftazidime and cloxacillin). Candida species accounted for the majority of the fungal findings: 62% of the fecal and 78% in the throat. A total of 170 clinical infection episodes were recorded, and in 12 of these, the bacterial blood culture was positive. In 4/12 cases, the pathogen was detected in surveillance culture previously, leading to sensitivity and specificity of 33.3 and 47.4%, respectively. Positive predictive value of bacterial surveillance cultures was 0.9%. The antimicrobial treatment was changed in only five cases based on the surveillance culture results. Weekly surveillance cultures seldom provided clinical benefit and were not cost-effective.

Identification of a metagenomic gene cluster containing a new class A beta‐lactamase and toxin‐antitoxin systems

Several reports mention the presence of antibiotic resistance genes in natural and polluted environments, but many studies are based on their detection via polymerase chain reaction (PCR amplification of known genes and not on an activity screening. We constructed a metagenomic fosmid bank from DNA isolated from a polluted river in Brussels, Belgium, the Zenne. A total of 120,000 clones were pooled and plated directly on solid media containing different antibiotics. Several clones were isolated which could grow in the presence of ampicillin. The DNA from several clones was extracted and subjected to restriction analysis and, based on their restriction pattern, two different clones were found. One of the clones was selected for further study as it showed a higher level of resistance to different β-lactams antibiotics (ticarcilline and ceftazidime). To find out which gene is responsible for the resistance, an in vitro transposon mutagenesis was performed and clones having lost the resistance phenotype were analyzed via inverse PCR amplification. Several clones had an insert in a gene encoding a new type of β-lactamase. The amplified fosmid DNA was fully sequenced revealing an insert of 41 kb containing 39 open reading frames (ORFs). Transposon insertions inactivating the resistance to β-lactams were also found in the ORF upstream of the blaA gene, encoding an aminotransferase, suggesting a polar effect on the transcription of the gene downstream. In addition, other genes were found such as histidine biosynthesis genes, which were found to be scattered on the insert, a relA/spoT gene, and genes belonging to type II toxin–antitoxin system. This predicted system was experimentally validated in Escherichia coli using an inducible expression system.