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

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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Mycoplasma pneumoniae may cause dyspnoea and hospitalisations in young healthy adults

European Journal of Clinical Microbiology & Infectious Diseases ◽

10.1007/s10096-021-04171-z ◽

2021 ◽

Author(s):

Riku Metsälä ◽

Solja Ala-Korpi ◽

Juha Rannikko ◽

Merja Helminen ◽

Marjo Renko

Keyword(s):

Respiratory Tract ◽

Mycoplasma Pneumoniae ◽

Hospital Setting ◽

Health Condition ◽

Clinical Findings ◽

Antimicrobial Treatment ◽

University Hospital ◽

Upper Respiratory Tract ◽

Beta Lactam ◽

Beta Lactam Antibiotics

AbstractPolymerase chain reaction (PCR)-based diagnostics for Mycoplasma pneumoniae (M. pneumoniae) from the respiratory tract has become widely available, but the interpretation of the results remains unclear. M. pneumoniae has been suggested to cause mainly mild and self-limiting infections or asymptomatic carriage. However, systematic analyses of the association between PCR results and clinical findings are scarce. This study aimed to clarify the clinical features of PCR-positive M. pneumoniae infections in a hospital setting. We reviewed 103 PCR-positive patients cared for in a university hospital during a 3-year period. Data on age, sex, health condition, acute symptoms, other pathogens found, laboratory and X-ray results and treatments were collected. Over 85% of the patients had a triad of typical symptoms: fever, cough and shortness of breath. Symptoms in the upper respiratory tract were rare. In 91% of the cases, M. pneumoniae was the only pathogen found. The highest incidence was found in the age group of 30–40 years, and 68% of the patients did not have any underlying diseases. Most patients were initially empirically treated with beta-lactam antibiotics and needed 2–4 changes in their treatment. Only 6% were discharged without an antibiotic effective against M. pneumoniae. This study shows that M. pneumoniae often led to hospitalisation and that patients needed appropriate antimicrobial treatment to recover. Mixed infections were rare, and situations that could be interpreted as carriage did not occur.

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Species-Specific Sensitivity of Coagulase-Negative Staphylococci to Single Antibiotics and Their Combinations

Polish Journal of Microbiology ◽

10.33073/pjm-2011-022 ◽

2011 ◽

Vol 60 (2) ◽

pp. 155-161 ◽

Cited By ~ 4

Author(s):

GRAŻYNA SZYMAŃSKA ◽

MAGDALENA SZEMRAJ ◽

ELIGIA M. SZEWCZYK

Keyword(s):

University Hospital ◽

Hospital Environment ◽

Beta Lactam ◽

Coagulase Negative Staphylococci ◽

Methicillin Resistant ◽

Beta Lactam Antibiotics ◽

Resistant Strains ◽

Staphylococcus Hominis ◽

Species Specific

The activity of beta-lactam antibiotics (oxacillin, cloxacillin, cephalotin), vancomycin, gentamicin and rifampicin applied in vitro individually and in combination against 37 nosocomial methicillin-resistant strains of coagulase-negative staphylococci (CNS) was assessed to demonstrate the heterogeneity of this group of bacteria and estimate the chance of the efficacy of such therapy. The strains belonged to four species: Staphylococcus epidermidis, Staphylococcus haemolyticus, Staphylococcus cohnii, Staphylococcus hominis. They originated from a hospital environment and from the skin of medical staff of the intensive care unit of a paediatric ward at a university hospital. All strains were methicillin-resistant, according to CLSI standards, but individual strains differed in MIC(ox) values. Susceptibility to other tested antibiotics was also characteristic for the species. The increased susceptibility to antibiotics in combinations, tested by calculating the fractional inhibitory concentration (FIC) index, concerned 26 out of 37 investigated strains and it was a feature of a particular species. Combinations of vancomycin and cephalotin against S. epidermidis and oxacillin with vancomycin were significant, as well as cephalotin and rifampicin in growth inhibition of multiresistant S. haemolyticus strains.

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

10.1101/2020.11.09.373787 ◽

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.

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

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01267-20 ◽

2020 ◽

Vol 64 (11) ◽

Cited By ~ 1

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.

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Suspected penicillin allergy: risk assessment using an algorithm as an antibiotic stewardship project

Allergo Journal International ◽

10.1007/s40629-020-00135-5 ◽

2020 ◽

Vol 29 (6) ◽

pp. 174-180

Author(s):

Christiane Querbach ◽

Tilo Biedermann ◽

Dirk H. Busch ◽

Rüdiger Eisenhart-Rothe ◽

Susanne Feihl ◽

...

Keyword(s):

Risk Stratification ◽

Bacterial Infections ◽

University Hospital ◽

Beta Lactam ◽

Delayed Reaction ◽

Allergy Testing ◽

Beta Lactam Antibiotics ◽

Patient Reported ◽

Provocation Testing ◽

Reliable Solution

Summary Background Beta-lactam antibiotics (BLA) are the treatment of choice for a large number of bacterial infections. Putative BLA allergies are often reported by patients, but rarely confirmed. Many patients do not receive BLA due to suspected allergy. There is no systematic approach to risk stratification in the case of a history of suspected BLA allergy. Methods Using the available stratification programs and taking current guidelines into account, an algorithm for risk stratification, including recommendations on the use of antibiotics in cases of compellingly indicated BLA despite suspected BLA allergy, was formulated by the authors for their maximum care university hospital. Results The hospital is in great need of recommendations on how to deal with BLA allergies. Patient-reported information in the history forms the basis for classifying the reactions into four risk categories: (1) BLA allergy excluded, (2) benign delayed reaction, (3) immediate reaction, and (4) severe cutaneous and extracutaneous drug reaction. Recommendations strictly depend on this classification and range from use of full-dose BLA or use of BLA under certain conditions (e.g., two-stage dose escalation, non-cross-reactive BLA only) to prohibiting all BLA and the use of alternative non-BLA. In case of suspected immediate or delayed allergic reactions, there is an additional recommendation regarding subsequent allergy testing during a symptom-free interval. Conclusion Triage of patients with suspected BLA is urgently required. While allergy testing, including provocation testing, represents the most reliable solution, this is not feasible in all patients due to the high prevalence of BLA allergies. The risk stratification algorithm developed for the authors’ hospital represents a tool suitable to making a contribution to rational antibiotic therapy.

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

Agricultural and Biological Chemistry ◽

10.1271/bbb1961.50.839 ◽

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

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Beta-Lactam Hypersensitivity and Cross-Reactivity

Journal of Pharmacy Practice ◽

10.1177/0897190014546109 ◽

2014 ◽

Vol 27 (6) ◽

pp. 530-544 ◽

Cited By ~ 27

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.

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Morphological deconvolution of beta-lactam polyspecificity inE. coli

10.1101/545335 ◽

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.

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Beta-lactam Resistance Mechanisms in Pathogens Isolated from Patients Admitted to Intensive Care Unit

Revista de Chimie ◽

10.37358/rc.17.6.5646 ◽

2017 ◽

Vol 68 (6) ◽

pp. 1225-1228

Author(s):

Carmen Axente ◽

Delia Muntean ◽

Luminita Baditoiu ◽

Roxana Moldovan ◽

Elena Hogea ◽

...

Keyword(s):

Intensive Care Unit ◽

Intensive Care ◽

Antimicrobial Resistance ◽

Resistance Mechanisms ◽

University Hospital ◽

Beta Lactam ◽

Extended Spectrum Beta Lactamase ◽

Beta Lactam Antibiotics ◽

Current Context ◽

A Prospective Study

Intensive care units (ICUs) are often referred to as the epicentre of infection diseases in a hospital. Many studies highlighted the importance of using local antimicrobial resistance data, to guide empirical antibiotic therapy. As a consequence, the present study is particularly important, especially in the current context, when we are witnessing an ascending trend of antimicrobial resistance. Beta-lactams are the most frequently used class of antibiotics for treating patients infected with various germs. The aim of this study is to analyse the modalities by which microorganisms become resistant to antibiotics of this class, in an intensive care unit of a Romanian university hospital. During the period between January, the 1st 2012 and December the 31st 2013, a prospective study was conducted in the largest ICU from the Western part of Romania. Various resistance mechanisms to beta-lactam antibiotics were detected. Among these, there is great concern regarding the high number of extended-spectrum beta-lactamase producing microorganisms, as in most cases they determine the use of carbapenems, thus increasing the risk of occurrence and dissemination of carbapenemase-producing bacteria.

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The Ultra-Broad-Spectrum Beta-lactamase Inhibitor QPX7728 Restores the Potency of Multiple Oral Beta-lactam Antibiotics against Beta-lactamase Producing Strains of Resistant Enterobacterales

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.02168-21 ◽

2021 ◽

Author(s):

Olga Lomovskaya ◽

Debora Rubio-Aparicio ◽

Ruslan Tsivkovski ◽

Jeff Loutit ◽

Michael Dudley

Keyword(s):

Broad Spectrum ◽

Resistance Mechanisms ◽

Beta Lactamase ◽

Beta Lactam ◽

Beta Lactams ◽

Intrinsic Resistance ◽

Beta Lactamases ◽

Beta Lactam Antibiotics ◽

The Impact ◽

Lactamase Inhibitor

QPX7728 is a cyclic boronate ultra-broad-spectrum beta-lactamase inhibitor, with potent activity against both serine and metallo beta-lactamases. QPX7728 can be delivered systemically by the IV or oral route of administration. Oral β-lactam antibiotics alone or in combination with QPX7728 were evaluated for 1) sensitivity to hydrolysis by various common beta-lactamases and inhibition of hydrolysis by QPX7728; 2) the impact of non-beta-lactamase-mediated resistance mechanisms on potency of beta-lactams; and 3) in vitro activity against a panel of clinical strains producing diverse beta-lactamases. The carbapenem tebipenem had stability for many serine beta-lactamases from all molecular classes followed by cephalosporin ceftibuten. Addition of QPX7728 to tebipenem, ceftibuten and mecillinam completely reversed beta-lactamase-mediated resistance in cloned beta-lactamases from serine and metallo enzyme classes; the degree of potentiation of other beta-lactams varied according to the beta-lactamase produced. Tebipenem, ceftibuten and cefixime had the lowest MICs against laboratory strains with various combinations of beta-lactamases and the intrinsic drug-resistance mechanisms of porin and efflux mutations. There was a high degree of correlation between potency of various combinations against cloned beta-lactamases and efflux/porin mutants and the activity against clinical isolates, showing the importance of both inhibition of beta-lactamase along with minimal impact of general intrinsic resistance mechanisms affecting the beta-lactam. Tebipenem and ceftibuten appeared to be the best beta-lactam antibiotics when combined with QPX7728 for activity against Enterobacterales that produce serine or metallo beta-lactamases.

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