Role of Aminoglycosides in Face of Introduction of New Beta-Lactam Antibiotics in Treatment of Nosocomial Infection

1983 ◽  
Vol 4 (6) ◽  
pp. 440-443
Author(s):  
John E. McGowan ◽  
David B. McClellan ◽  
Paula S. Irwin
Keyword(s):  
Nosocomial Infection ◽  
Wide Spectrum ◽  
Empiric Therapy ◽  
Beta Lactam ◽  
Beta Lactams ◽  
Suspected Sepsis ◽  
Single Drug ◽  
Beta Lactam Antibiotics ◽  
Susceptibility Profiles

AbstractAminoglycosides often are employed for empiric therapy of nosocomial infection because of their activity against a wide spectrum of gram-negative aerobic bacilli (GNAB). New beta-lactam antimicrobials also are active against many GNAB. As toxicity appears less likely for the beta-lactams than for aminoglycosides, their use might be preferable if susceptibility profiles were equivalent.We studied susceptibility of 90 GNAB recovered from blood culture during a three-month period. All were susceptible to aminoglycosides; 93% were susceptible to at least one of the following: ampicillin, carbenicillin, ticarcillin, cephalothin, chloramphenicol or trimethoprim-sulfamethoxazole. All were susceptible to at least one of our newer beta-lactams (cefamandole, cefoxitin, cefotaxime, moxalactam, piperacillin), but the percentage susceptible to any single beta-lactam was lower than that for any of the aminoglycosides tested. All of the isolates were susceptible to combinations of two beta-lactam drugs.In our hospital, beta-lactams may be reasonable alternatives to aminoglycosides in selected cases where susceptibility has been demonstrated. However, aminoglycosides continue to provide the broadest single-drug coverage for empiric therapy of known or suspected sepsis with GNAB. The utility of combinations of beta-lactam drugs for empiric therapy requires further assessment by clinical trials.

scholarly journals Inherent protection of bacteria from beta-lactam antibiotics by wet-dry cycles with microscopic surface wetness

2020 ◽  
Author(s):  
Yana Beizman-Magen ◽  
Maor Grinberg ◽  
Tomer Orevi ◽  
Nadav Kashtan
Keyword(s):  
Model Organism ◽  
Liquid Films ◽  
Interspecies Interactions ◽  
Beta Lactam ◽  
Beta Lactams ◽  
Surface Wetness ◽  
Beta Lactam Antibiotics ◽  
Hygroscopic Salts ◽  
Antibiotic Response ◽  
Microscopic Surface

AbstractA large portion of bacterial life occurs on surfaces that are not constantly saturated with water and experience recurrent wet-dry cycles. While soil, plant leaves and roots, and many indoor surfaces may appear dry when not saturated with water, they are in fact often covered by thin liquid films and microdroplets, invisible to the naked eye, known as microscopic surface wetness (MSW). Such MSW, resulting from the condensation of water vapor to hygroscopic salts, is ubiquitous yet largely underexplored. A wide variety of antibiotics are abundant in environments where MSW occurs, yet little is known about bacterial response to antibiotics in wet-dry cycles and under MSW conditions. Using E. coli as a model organism, we show, through a combination of experiments and computational modeling, that bacteria are considerably more protected from beta-lactams under wet-dry cycles with MSW phases, than they are under constantly wet conditions. This is due to the combined effect of several mechanisms, including tolerance triggered by inherent properties of MSW, i.e., high salt concentrations and slow cell growth, and the deactivation of antibiotics due to physicochemical properties of MSW. Remarkably, we also find evidence for a cross-protection effect, where addition of lethal doses of antibiotic before drying significantly increases cells’ survival under MSW. As wet-dry cycles with MSW and beta-lactams, as well as other antibiotics, are common in vast terrestrial microbial habitats, our findings are expected to have significant implications for how we understand antibiotic response, population dynamics, and interspecies interactions in these globally important microbial ecosystems.

scholarly journals In Vivo Activity of QPX7728, an Ultrabroad-Spectrum Beta-Lactamase Inhibitor, in Combination with Beta-Lactams against Carbapenem-Resistant Klebsiella pneumoniae

2020 ◽  
Vol 64 (11) ◽  
Author(s):  
Mojgan Sabet ◽  
Ziad Tarazi ◽  
David C. Griffith
Keyword(s):  
Klebsiella Pneumoniae ◽  
Beta Lactamase ◽  
Beta Lactam ◽  
Beta Lactams ◽  
Bacterial Killing ◽  
Clinical Issue ◽  
Content Type ◽  
Beta Lactam Antibiotics ◽  
Carbapenem Resistant ◽  
Lactamase Inhibitor

ABSTRACT Resistance to beta-lactams has created a major clinical issue. QPX7728 is a novel ultrabroad-spectrum cyclic boronic acid beta-lactamase inhibitor with activity against both serine and metallo-beta-lactamases developed to address this resistance for use in combination with beta-lactam antibiotics. The objective of these studies was to evaluate the activity of QPX7728 in combination with multiple beta-lactams against carbapenem-resistant Klebsiella pneumoniae isolates in a neutropenic mouse thigh infection model. Neutropenic mice were infected with strains with potentiated beta-lactam MICs of ≤2 mg/liter in the presence of 8 mg/liter QPX7728. Two strains of carbapenem-resistant K. pneumoniae were tested with aztreonam, biapenem, cefepime, ceftazidime, ceftolozane, and meropenem alone or in combination with 12.5, 25, or 50 mg/kg of body weight of QPX7728 every 2 hours for 24 hours. Treatment with all beta-lactams alone either was bacteriostatic or allowed for bacterial growth. The combination of QPX7728 plus each of these beta-lactams produced bacterial killing at all QPX7728 doses tested. Overall, these data suggest that QPX7728 administered in combination with different partner beta-lactam antibiotics may have utility in the treatment of bacterial infections due to carbapenem-resistant K. pneumoniae.

Motile Aeromonas as agent of infections of the foot

1995 ◽  
Vol 85 (9) ◽  
pp. 505-508 ◽  
Author(s):  
M Wakabongo
Keyword(s):  
Second Generation ◽  
Antimicrobial Agents ◽  
Third Generation ◽  
Beta Lactam ◽  
Beta Lactam Antibiotics ◽  
Taxonomic Uncertainty ◽  
Post Traumatic ◽  
Third Generation Cephalosporins

Motile Aeromonas infections of the foot are caused mostly by post-traumatic incidence, occurring mostly during summer months. Serious complications such as osteomyelitis and amputation can result if the infections go untreated or are inadequately treated. The role of each species of motile Aeromonas in pathogenesis and response to antimicrobial agents is not well understood because of taxonomic uncertainty. As a group, motile Aeromonas respond well to aminoglycosides, second-generation and third-generation cephalosporins, quinolones, and some beta-lactam antibiotics.

scholarly journals Studies on monocyclic .BETA.-lactam antibiotics. Part I. Synthesis of 4-substituted monocyclic .BETA.-lactams by a lewis acid-mediated reaction.

1986 ◽  
Vol 50 (4) ◽  
pp. 839-846
Author(s):  
Chosaku YOSHIDA ◽  
Takako HORI ◽  
Kaishu MOMONOI ◽  
Kiyoshi TANAKA ◽  
Sumiko KISHIMOTO ◽  
...  
Keyword(s):  
Lewis Acid ◽  
Beta Lactam ◽  
Beta Lactams ◽  
Beta Lactam Antibiotics

Beta-Lactam Hypersensitivity and Cross-Reactivity

2014 ◽  
Vol 27 (6) ◽  
pp. 530-544 ◽  
Author(s):  
Adrienne T. Terico ◽  
Jason C. Gallagher
Keyword(s):  
Retrospective Studies ◽  
Immunoglobulin E ◽  
Cross Reactivity ◽  
Side Chains ◽  
Beta Lactam ◽  
Beta Lactams ◽  
Medline Search ◽  
Beta Lactam Antibiotics ◽  
Drug Classes

Penicillin is the most frequently reported cause of drug allergy, and cross-reactivity of penicillins with other beta-lactam antibiotics is an area of debate. This review evaluates the available data on immunoglobulin E-mediated penicillin hypersensitivity and cross-reactivity with cephalosporin, carbapenem, and monobactam antibiotics. A MEDLINE search was conducted from 1950 to October 2013, and selected references from review articles were also evaluated. There is a wide variety in reported incidences of cross-reactivity between penicillins and cephalosporins or carbapenems, with early retrospective studies suggesting up to 41.7% and 47.4% cross-reactivity, respectively. Conversely, the use of monobactam antibiotics is frequently employed in the case of a penicillin allergy, as prescribers believe that there is no cross-reactivity between the 2 drug classes. More recent prospective studies suggest that the rates of cross-reactivity with cephalosporins and carbapenems are <5% and <1%, respectively. Similarities in penicillin and cephalosporin side chains may play a role in cross-reactivity between these classes. Cross-reactivity with monobactams is essentially negligible; however, there are some clinical data to support an interaction between ceftazidime and aztreonam, due to the similarity of their side chains. The data reviewed suggest that avoidance of other beta-lactams in patients with type 1 hypersensitivity to penicillins should be reconsidered.

scholarly journals Morphological deconvolution of beta-lactam polyspecificity inE. coli

2019 ◽  
Author(s):  
William J. Godinez ◽  
Helen Chan ◽  
Imtiaz Hossain ◽  
Cindy Li ◽  
Srijan Ranjitkar ◽  
...  
Keyword(s):  
Ex Situ ◽  
Exact Nature ◽  
Enzyme Specificity ◽  
Beta Lactam ◽  
Beta Lactams ◽  
Penicillin Binding Proteins ◽  
E Coli ◽  
Beta Lactam Antibiotics ◽  
Cell Extracts ◽  
The Family

AbstractBeta-lactam antibiotics comprise one of the earliest known classes of antibiotic therapies. These molsecules covalently inhibit enzymes from the family of penicillin-binding proteins, which are essential to the construction of the bacterial cell wall. As a result, beta-lactams have long been known to cause striking changes to cellular morphology. The exact nature of the changes tend to vary by the precise PBPs engaged in the cell since beta-lactams exhibit a range of PBP enzyme specificity. The traditional method for exploring beta-lactam polyspecificity is a gel-based binding assay which is low-throughput and typically runex situin cell extracts. Here, we describe a medium-throughput, image-based assay combined with machine learning methods to automatically profile the activity of beta-lactams inE. colicells. By testing for morphological change across a panel of strains with perturbations to individual PBP enzymes, our approach automatically and quantifiably relates different beta-lactam antibiotics according to their preferences for individual PBPs in cells. We show the potential of our approach for guiding the design of novel inhibitors towards different PBP-binding profiles by recapitulating the activity of two recently-reported PBP inhibitors.

scholarly journals Synergy Between Beta-Lactams and Lipo-, Glyco-, and Lipoglycopeptides, Is Independent of the Seesaw Effect in Methicillin-Resistant Staphylococcus aureus

2021 ◽  
Vol 8 ◽  
Author(s):  
Rutan Zhang ◽  
Ismael A. Barreras Beltran ◽  
Nathaniel K. Ashford ◽  
Kelsi Penewit ◽  
Adam Waalkes ◽  
...  
Keyword(s):  
Synergistic Effects ◽  
Clinical Importance ◽  
Synergistic Activity ◽  
Beta Lactam ◽  
Beta Lactams ◽  
Methicillin Resistant ◽  
Penicillin Binding Proteins ◽  
The Impact ◽  
Isogenic Strains

Methicillin-resistant S. aureus (MRSA) are resistant to beta-lactams, but synergistic activity between beta-lactams and glycopeptides/lipopeptides is common. Many have attributed this synergy to the beta-lactam-glycopeptide seesaw effect; however, this association has not been rigorously tested. The objective of this study was to determine whether the seesaw effect is necessary for synergy and to measure the impact of beta-lactam exposure on lipid metabolism. We selected for three isogenic strains with reduced susceptibility to vancomycin, daptomycin, and dalbavancin by serial passaging the MRSA strain N315. We used whole genome sequencing to identify genetic variants that emerged and tested for synergy between vancomycin, daptomycin, or dalbavancin in combination with 6 beta-lactams with variable affinity for staphylococcal penicillin binding proteins (PBPs), including nafcillin, meropenem, ceftriaxone, ceftaroline, cephalexin, and cefoxitin, using time-kills. We observed that the seesaw effect with each beta-lactam was variable and the emergence of the seesaw effect for a particular beta-lactam was not necessary for synergy between that beta-lactam and vancomycin, daptomycin, or dalbavancin. Synergy was more commonly observed with vancomycin and daptomycin based combinations than dalbavancin in time-kills. Among the beta-lactams, cefoxitin and nafcillin were the most likely to exhibit synergy using the concentrations tested, while cephalexin was the least likely to exhibit synergy. Synergy was more common among the resistant mutants than the parent strain. Interestingly N315-D1 and N315-DAL0.5 both had mutations in vraTSR and walKR despite their differences in the seesaw effect. Lipidomic analysis of all strains exposed to individual beta-lactams at subinhibitory concentrations suggested that in general, the abundance of cardiolipins (CLs) and most free fatty acids (FFAs) positively correlated with the presence of synergistic effects while abundance of phosphatidylglycerols (PGs) and lysylPGs mostly negatively correlated with synergistic effects. In conclusion, the beta-lactam-glycopeptide seesaw effect and beta-lactam-glycopeptide synergy are distinct phenomena. This suggests that the emergence of the seesaw effect may not have clinical importance in terms of predicting synergy. Further work is warranted to characterize strains that don’t exhibit beta-lactam synergy to identify which strains should be targeted with combination therapy and which ones cannot and to further investigate the potential role of CLs in mediating synergy.

scholarly journals Biochemical profile and resistance phenotype of bacteria isolated from the operating site departments of the National Reference University Hospital of N’Djamena

2021 ◽  
Vol 10 (1) ◽  
pp. 381-396
Author(s):  
Bessimbaye Nadlaou ◽  
Djimadoum Mbanga ◽  
Issakou Bakarnga-Via ◽  
Claude Oualé ◽  
Nicolas Barro ◽  
...  
Keyword(s):  
Average Rate ◽  
University Hospital ◽  
Beta Lactam ◽  
Beta Lactams ◽  
Surgical Services ◽  
National Reference ◽  
Beta Lactam Antibiotics ◽  
Medical Microbiology ◽  
Normal Period ◽  
Staphylococcus Spp

The aim is to assess the level of contamination of wound bacteria in operated patients in the surgical departments of the National Reference University Hospital (CHURN) of N’Djamena. From August 1, 2018 to August 1, 2019, an observational culture study on wound pus was carried out in patients operated on from the surgical services of the N’Djamena CHURN according to standard methods of medical microbiology. Of the 1092 patients operated on, 565 patients were released within a normal period of hospitalization and 527 in contact with the pathogens were maintained. Significant differences were observed between the proportions of positive (86%) and sterile (14%) cultures; female (30.36%) and male (69.63%) operated subjects with probabilities of 0.02 and 0.001 respectively. Escherichia coli were the most common germs (32.7%), followed by Staphylococcus spp (20.9%). The bacteria isolated were resistant to beta-lactam antibiotics at an average rate of 40%, only imipenem, a last-resort antibiotic, was very sensitive (99.5%). In view of these results, we recommend that prescribers avoid prescribing antibiotics without laboratory evidence for fear of losing the beta-lactams permanently.

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