Hematological Effects Associated with Beta-Lactam Use

1986 ◽  
Vol 20 (11) ◽  
pp. 833-836 ◽  
Author(s):  
Lesia M. Babiak ◽  
Michael J. Rybak
Keyword(s):  
Coagulation Cascade ◽  
Close Monitoring ◽  
Beta Lactam ◽  
Beta Lactams ◽  
Drug Induced ◽  
Antimicrobial Spectrum ◽  
Beta Lactam Antibiotics ◽  
Normal Platelet ◽  
Hematological Effects ◽  
Life Threatening

Beta-lactam antibiotics have continued to be the mainstay of antiinfective treatment. Newer agents, such as the third-generation cephalosporins or ureidopenicillins, have the advantage of a broader antimicrobial spectrum and improved pharmacokinetics. The beta-lactams are often promoted as alternatives to more toxic antibiotic regimens. However, several of the beta-lactams have been shown to produce hematological effects, some of which can be life threatening. The primary hematological effects appear to be inhibition of normal platelet function and the coagulation cascade, which is reflected by changes in bleeding times and increases in prothrombin time and activated partial thromboplastin time, respectively. Although not all patients will develop bleeding problems associated with these agents, close monitoring of patients with risk factors for bleeding and dosage adjustments may help to avert these drug-induced hematological problems.

scholarly journals Beta-Lactams Toxicity in the Intensive Care Unit: An Underestimated Collateral Damage?

2021 ◽  
Vol 9 (7) ◽  
pp. 1505
Author(s):  
Claire Roger ◽  
Benjamin Louart
Keyword(s):  
Risk Factors ◽  
Intensive Care Unit ◽  
Intensive Care ◽  
Clinical Manifestations ◽  
Acute Interstitial Nephritis ◽  
Convulsive Status Epilepticus ◽  
Beta Lactam ◽  
Beta Lactams ◽  
Drug Induced ◽  
Icu Patients

Beta-lactams are the most commonly prescribed antimicrobials in intensive care unit (ICU) settings and remain one of the safest antimicrobials prescribed. However, the misdiagnosis of beta-lactam-related adverse events may alter ICU patient management and impact clinical outcomes. To describe the clinical manifestations, risk factors and beta-lactam-induced neurological and renal adverse effects in the ICU setting, we performed a comprehensive literature review via an electronic search on PubMed up to April 2021 to provide updated clinical data. Beta-lactam neurotoxicity occurs in 10–15% of ICU patients and may be responsible for a large panel of clinical manifestations, ranging from confusion, encephalopathy and hallucinations to myoclonus, convulsions and non-convulsive status epilepticus. Renal impairment, underlying brain abnormalities and advanced age have been recognized as the main risk factors for neurotoxicity. In ICU patients, trough concentrations above 22 mg/L for cefepime, 64 mg/L for meropenem, 125 mg/L for flucloxacillin and 360 mg/L for piperacillin (used without tazobactam) are associated with neurotoxicity in 50% of patients. Even though renal complications (especially severe complications, such as acute interstitial nephritis, renal damage associated with drug induced hemolytic anemia and renal obstruction by crystallization) remain rare, there is compelling evidence of increased nephrotoxicity using well-known nephrotoxic drugs such as vancomycin combined with beta-lactams. Treatment mainly relies on the discontinuation of the offending drug but in the near future, antimicrobial optimal dosing regimens should be defined, not only based on pharmacokinetics/pharmacodynamic (PK/PD) targets associated with clinical and microbiological efficacy, but also on PK/toxicodynamic targets. The use of dosing software may help to achieve these goals.

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.

Cloxacillin-Induced Acute Tubulo Interstitial Nephritis

1992 ◽  
Vol 26 (10) ◽  
pp. 1241-1242 ◽  
Author(s):  
Roberto García-Ortiz ◽  
Roberto S. Espinoza ◽  
Gonzalo R. Silva ◽  
Rodrigo K. Alonso ◽  
Hector S. Opazo ◽  
...  
Keyword(s):  
Renal Function ◽  
Interstitial Nephritis ◽  
Case Reports ◽  
Urinary Output ◽  
Lumbar Pain ◽  
Dramatic Improvement ◽  
Beta Lactam ◽  
Drug Induced ◽  
Beta Lactam Antibiotics ◽  
Sterile Pyuria

OBJECTIVE: To report a case of possible cloxacillin-induced acute tubulo interstitial nephritis (AIN). CASE SUMMARY: A 15-year-old male patient presented with hypertension, edema, lumbar pain, sterile pyuria, eosinophiluria (ten percent), and severe renal dysfunction three months after the ingestion of cloxacillin. A renal biopsy revealed diffuse edema and inflammatory infiltrate of the interstitium (five percent eosinophils). He received four sessions of peritoneal dialysis with dramatic improvement in urinary output and renal function. His biochemical parameters returned to normal values 21 days after admission, without the use of glucocorticosteroids. DISCUSSION: Published case reports on AIN induced by penicillin and related drugs are reviewed and compared. The role of interstitial edema in acute renal failure associated with drug-induced AIN is mentioned. CONCLUSIONS: AIN is a rare but significant complication of therapy with penicillin and related drugs. The clinical picture is similar for all of these drugs, but skin rash and fever are absent in AIN induced by cloxacillin and cloxacillin-related drugs. Dialysis improved the patient's urinary output and renal function. Beta-lactam antibiotics should be avoided in patients with cloxacillin-induced AIN.

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 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.

scholarly journals Amoxicillin induced toxic epidermal necrolysis

2020 ◽  
Vol 9 (3) ◽  
pp. 510
Author(s):  
Lakshmi Narasimha G. ◽  
Kalpana P.
Keyword(s):  
Adverse Drug Reaction ◽  
Drug Reaction ◽  
Toxic Epidermal Necrolysis ◽  
Broad Spectrum ◽  
Beta Lactam ◽  
Beta Lactams ◽  
Beta Lactam Antibiotic ◽  
Lactam Antibiotic ◽  
Life Threatening ◽  
Inflammatory Drugs

Toxic epidermal necrolysis (TEN) is a rare life-threatening adverse drug reaction associated with mucocutaneous eruptions and peeling of skin (sloughing) mostly caused by drugs like sulphonamides, beta lactams, carbamazepine and non-steroidal anti-inflammatory drugs (NSAIDs). Amoxicillin is a broad spectrum, bactericidal, Beta-lactam antibiotic used in treatment of various infections. Here by we have reported the case of amoxicillin induced severe toxic epidermal necrolysis. A Patient admitted in the hospital with the symptoms of epidermal sloughing that resulted in bare dermis as he received Amoxicillin drug for his diagnosis of fever. After clear examination TEN was confirmed and suspected with the cause due to Amoxicillin. The drug was stopped and patient was treated with other drugs for symptomatic cure. The patient was recovered from his condition and improved significantly.

scholarly journals High Heterogeneity of Multidrug-Resistant Enterobacteriaceae Fecal Levels in Hospitalized Patients Is Partially Driven by Intravenous β-Lactams

2019 ◽  
Vol 64 (2) ◽  
Author(s):  
Ana Djukovic ◽  
Eva M. González-Barberá ◽  
Jaime Sanz ◽  
Alejandro Artacho ◽  
Iván Peñaranda ◽  
...  
Keyword(s):  
Clinical Decision Making ◽  
Direct Action ◽  
Clinical Decision ◽  
Multidrug Resistant ◽  
Hospitalized Patients ◽  
Beta Lactam ◽  
Beta Lactams ◽  
Susceptibility Data ◽  
Life Threatening ◽  
Third Generation Cephalosporins

ABSTRACT Multidrug-resistant Enterobacteriaceae (MRE) colonize the intestine asymptomatically from where they can breach into the bloodstream and cause life-threatening infections, especially in heavily colonized patients. Despite the clinical relevance of MRE colonization levels, we know little about how they vary in hospitalized patients and the clinical factors that determine those levels. Here, we conducted one of the largest studies of MRE fecal levels by tracking longitudinally 133 acute leukemia patients and monitoring their MRE levels over time through extensive culturing. MRE were defined as Enterobacteriaceae species that acquired nonsusceptibility to ≥1 agent in ≥3 antimicrobial categories. In addition, due to the selective media used, the MRE had to be resistant to third-generation cephalosporins. MRE were detected in 60% of the patients, but their fecal levels varied considerably among patients and within the same patient (>6 and 4 orders of magnitude, respectively). Multivariate analysis of clinical metadata revealed an impact of intravenous beta-lactams (i.e., meropenem and piperacillin-tazobactam), which significantly diminished the fecal MRE levels in hospitalized patients. Consistent with a direct action of beta-lactams, we found an effect only when the patient was colonized with strains sensitive to the administered beta-lactam (P < 0.001) but not with nonsusceptible strains. We report previously unobserved inter- and intraindividual heterogeneity in MRE fecal levels, suggesting that quantitative surveillance is more informative than qualitative surveillance of hospitalized patients. In addition, our study highlights the relevance of incorporating antibiotic treatment and susceptibility data of gut-colonizing pathogens for future clinical studies and in clinical decision-making.

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