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The Journal of Antimicrobial... Oct 2023The blaZ gene encodes penicillinase, which inactivates penicillin. As there were reports on suboptimal sensitivity for the penicillin zone-edge test, a phenotypic method...
Treatment outcomes with benzylpenicillin and non-benzylpenicillin antibiotics, and the performance of the penicillin zone-edge test versus molecular detection of blaZ in penicillin-susceptible Staphylococcus aureus (PSSA) bacteraemia.
OBJECTIVES
The blaZ gene encodes penicillinase, which inactivates penicillin. As there were reports on suboptimal sensitivity for the penicillin zone-edge test, a phenotypic method for blaZ detection, we investigated treatment outcomes in patients with penicillin-susceptible Staphylococcus aureus (PSSA) bacteraemia (phenotypically negative for penicillinase), subjecting isolates to molecular testing for blaZ retrospectively.
PATIENTS AND METHODS
A retrospective cohort study was conducted on 121 patients with a first episode of PSSA bacteraemia from 1 January 2012 to 31 October 2015 at Tan Tock Seng Hospital (TTSH), Singapore. Patients were grouped into IV benzylpenicillin and non-benzylpenicillin groups. The primary outcome was overall treatment failure, defined as either 30 day all-cause mortality and/or 90 day relapse. The penicillin (P10) zone-edge test was repeated on archived PSSA isolates, concurrently with penicillin MIC determination via gradient diffusion and PCR for blaZ.
RESULTS
Among 121 patients, 57 patients (47.1%) received IV benzylpenicillin as the predominant antibiotic. There was no significant difference in overall treatment failure between treatment with the benzylpenicillin [7/57 (12.3%)] versus non-benzylpenicillin groups [12/64 (18.8%)] (P = 0.33) or cloxacillin/cefazolin [6/37 (16.2%)] (P = 0.59). For 112 PSSA isolates available for testing, repeat penicillin zone-edge testing was negative for penicillinase production, corroborating previous results. A single PSSA isolate with a negative penicillin zone-edge test was found to be positive for blaZ.
CONCLUSIONS
We found no differences in overall treatment failure between patients with PSSA bacteraemia treated with benzylpenicillin, anti-staphylococcal β-lactams cefazolin/cloxacillin and other antimicrobials, when using the penicillin zone-edge test as the phenotypic method for blaZ screening.
Topics: Humans; Anti-Bacterial Agents; Penicillins; Staphylococcus aureus; Retrospective Studies; Cefazolin; Penicillinase; Penicillin G; Staphylococcal Infections; Bacteremia; Treatment Outcome; Cloxacillin; Microbial Sensitivity Tests
PubMed: 37596905
DOI: 10.1093/jac/dkad263 -
Clinical Pharmacokinetics Jul 2021Piperacillin-tazobactam is a potent β-lactam/β-lactamase inhibitor antibiotic commonly prescribed in the intensive care unit setting. Admitted patients often show... (Review)
Review
Piperacillin-tazobactam is a potent β-lactam/β-lactamase inhibitor antibiotic commonly prescribed in the intensive care unit setting. Admitted patients often show large variability in treatment response due to multiple pathophysiological changes present in this population that alter the drug's pharmacokinetics. This review summarizes the population pharmacokinetic models developed for piperacillin-tazobactam and provides comprehensive data on current dosing strategies while identifying significant covariates in critically ill patients. A literature search on the PubMed database was conducted, from its inception to July 2020. Relevant articles were retained if they met the defined inclusion/exclusion criteria. A total of ten studies, published between 2009 and 2020, were eligible. One- and two-compartment models were used in two and eight studies, respectively. The lowest estimated piperacillin clearance value was 3.12 L/h, and the highest value was 19.9 L/h. The estimations for volume of distribution varied between 11.2 and 41.2 L. Tazobactam clearance values ranged between 5.1 and 6.78 L/h, and tazobactam volume of distribution values ranged between 17.5 and 76.1 L. The most frequent covariates were creatinine clearance and body weight, each present in four studies. Almost all studies used an exponential approach for the interindividual variability. The highest variability was observed in piperacillin central volume of distribution, at a value of 75.0%. Simulations showed that continuous or extended infusion methods performed better than intermittent administration to achieve appropriate pharmacodynamic targets. This review synthesizes important pharmacokinetic elements for piperacillin-tazobactam in an intensive care unit setting. This will help clinicians better understand changes in the drug's pharmacokinetic parameters in this specific population.
Topics: Anti-Bacterial Agents; Critical Illness; Humans; Intensive Care Units; Microbial Sensitivity Tests; Penicillanic Acid; Piperacillin; Prospective Studies; Tazobactam
PubMed: 33876381
DOI: 10.1007/s40262-021-01013-1 -
Revista Alergia Mexico (Tecamachalco,... Sep 2023The most commonly reported antibiotic allergy is penicillin. The false label of "allergy" to penicillin negatively affects the patient's quality of life and medical care. (Observational Study)
Observational Study
BACKGROUND
The most commonly reported antibiotic allergy is penicillin. The false label of "allergy" to penicillin negatively affects the patient's quality of life and medical care.
OBJECTIVE
To determine the frequency of allergy to penicillin and amoxicillin by in vivo exposure tests in patients with a history of immediate reaction to this class of medicinal products.
METHODS
Observational, cross-sectional, descriptive and prolective study in patients between 12 and 60 years of age with a history of immediate reaction to penicillin and/or amoxicillin. Prick and intradermal skin tests were performed with benzylpenicilloyl polylysine (Pre-Pen), penicillin G and oral challenge test with amoxicillin. The frequency of positivity and negativity in these tests was calculated with a 95% CI. Results were analyzed in Epi info 7.2.5.0.
RESULTS
In total 13 patients (10 women) were included, with a mean age of 39 years (SD 12.14). In 84.6% the last adverse drug reaction occurred 10 years ago and in all manifested with urticaria. The 38.4% confirmed penicillin allergy and the most frequent adverse reaction after in vivo tests was pruritus.
CONCLUSIONS
The clinical history alone is not sufficient, all patients with suspected penicillin allergy should be evaluated by in vivo exposure tests with major and minor determinants to corroborate or rule out allergy to this pharmacological class.
Topics: Adult; Female; Humans; Amoxicillin; Anti-Bacterial Agents; Cross-Sectional Studies; Drug Hypersensitivity; Penicillins; Quality of Life; Skin Tests; Urticaria; Male; Child; Adolescent; Young Adult; Middle Aged
PubMed: 37933946
DOI: 10.29262/ram.v70i3.1254 -
BMC Infectious Diseases Oct 2021Penicillin allergy prevalence is internationally reported to be around 10%. However, the majority of patients who report a penicillin allergy do not have a clinically...
BACKGROUND
Penicillin allergy prevalence is internationally reported to be around 10%. However, the majority of patients who report a penicillin allergy do not have a clinically significant hypersensitivity. Few patients undergo evaluation, which leads to overuse of broad-spectrum antibiotics. The objective of this study was to monitor prevalence and implement screening and testing of hospitalized patients.
METHODS
All patients admitted to the medical department in a local hospital in Oslo, Norway, with a self-reported penicillin allergy were screened using an interview algorithm to categorize the reported allergy as high-risk or low-risk. Patients with a history of low-risk allergy underwent a direct graded oral amoxicillin challenge to verify absence of a true IgE-type allergy.
RESULTS
257 of 5529 inpatients (4.6%) reported a penicillin allergy. 191 (74%) of these patients underwent screening, of which 86 (45%) had an allergy categorized as low-risk. 54 (63%) of the low-risk patients consented to an oral test. 98% of these did not have an immediate reaction to the amoxicillin challenge, and their penicillin allergy label could thus be removed. 42% of the patients under treatment with antibiotics during inclusion could switch to treatment with penicillins immediately after testing, in line with the national recommendations for antibiotic use.
CONCLUSIONS
The prevalence of self-reported penicillin allergy was lower in this Norwegian population, than reported in other studies. Screening and testing of hospitalized patients with self-reported penicillin allergy is a feasible and easy measure to de-label a large proportion of patients, resulting in immediate clinical and environmental benefit. Our findings suggest that non-allergist physicians can safely undertake clinically impactful allergy evaluations.
Topics: Amoxicillin; Drug Hypersensitivity; Humans; Penicillins; Pilot Projects; Skin Tests
PubMed: 34670500
DOI: 10.1186/s12879-021-06794-1 -
The Pan African Medical Journal 2023inappropriate use of antimicrobials is a cause for concern and contributes to the global antimicrobial resistance crises especially in Africa. This review aims to... (Review)
Review
INTRODUCTION
inappropriate use of antimicrobials is a cause for concern and contributes to the global antimicrobial resistance crises especially in Africa. This review aims to summarize the available evidence on the point prevalence and pattern of antimicrobial and/or antibiotic prescription in Africa.
METHODS
this review was carried out between April and September 2021 and identified published studies up until March 2021 on the point prevalence of antibiotic and/or antimicrobial use in Africa. Sources searched were OVID, PubMed, EMBASE, CINAHL, Web of Science, Google Scholar, Google, and African Journal Online (AJOL). Observational studies that reported prevalence published in English language were included. Covidence systematic review software was used for this review. A form for data extraction using domains culled from the Global Point Prevalence Survey of Antimicrobial Consumption and Resistance (Global-PPS) was developed on Covidence. Screening of studies for eligibility was done independently by two reviewers. Critical Appraisal tool for use in Joanna Briggs Institute (JBI) Systematic Reviews for prevalence studies was used for quality appraisal.
RESULTS
a total of 17 studies that met the inclusion criteria were included in the review. The overall prevalence of antimicrobial/antibiotic use among inpatients in these studies ranged from 40.7% to 97.6%. The median antimicrobial/antibiotic use was 61.3 [IQR= 45.5-72.1]. The highest use of antimicrobials was reported among studies from Nigeria with a prevalence of 97.6%. The most prescribed antibiotics were the beta-lactam penicillin (Amoxicillin, clavulanic acid) (86.9%), and third generation cephalosporins (55.0%). There was general preference for parenteral route of administration of the antimicrobial agents (40-70%). Use for community acquired infections (28.0-79.5%) was the main reason for use. Majority of the prophylactic use of antimicrobial agents were for surgical prophylaxis. the high prevalence of antimicrobial use in Africa reinforces the need for continued surveillance and concerted efforts to institutionalize and support antimicrobial stewardship for prescribers in health institutions in the African region.
Topics: Humans; Prevalence; Anti-Infective Agents; Anti-Bacterial Agents; Nigeria; Amoxicillin
PubMed: 37637407
DOI: 10.11604/pamj.2023.45.67.36191 -
The Journal of Applied Laboratory... Sep 2021The class of antibiotics known as β-lactams are a commonly used due to their effectiveness and safety. Therapeutic drug monitoring has been proposed but requires an...
BACKGROUND
The class of antibiotics known as β-lactams are a commonly used due to their effectiveness and safety. Therapeutic drug monitoring has been proposed but requires an accurate assay along with well-characterized preanalytic stability, as β-lactams are known to be relatively unstable.
METHODS
A high-throughput LC-MS/MS assay validation and stability study was performed for cefepime, meropenem, and piperacillin and tazobactam in serum. Patient samples, standards, and QCs were crashed with acetonitrile containing internal standard. Following centrifugation, an aliquot of the supernatant was diluted with clinical laboratory reagent water and analyzed by LC-MS/MS.
RESULTS
The assay showed linearity between 0.5 and 60 µg/mL for each analyte. The intra- and interassay reproducibility at 3 different concentrations (approximately 2, 25, and 40 µg/mL) was <5% for each analyte. Accuracy studies for each analyte were compared using linear regression and demonstrated: slope = 1.0 ± 0.1; r2 ≥ 0.980; and y intercept 95% CI that included zero. Minimal ion suppression or enhancement was observed, and no significant carryover was observed up to 500 µg/mL of each analyte. Stability studies demonstrated significant loss in serum for each analyte at ambient and refrigerated temperatures (2-8 °C) and at -20 °C over days or weeks. In contrast, when stored at -80 °C, no significant loss was observed.
CONCLUSIONS
The LC-MS/MS assay showed acceptable performance characteristics for quantitation of β-lactams. With well-characterized stability, this assay can be used with residual specimens for pharmacokinetic modeling, which may lead to individualized dosing and improved patient care.
Topics: Cefepime; Chromatography, Liquid; Humans; Meropenem; Piperacillin; Reproducibility of Results; Tandem Mass Spectrometry; Tazobactam
PubMed: 34086904
DOI: 10.1093/jalm/jfab036 -
Journal of AOAC International May 2023Antibiotics are used in ethanol production to discourage undesirable bacteria growth. To determine if antibiotic residues remain in the distillers grain (DG) byproduct,...
BACKGROUND
Antibiotics are used in ethanol production to discourage undesirable bacteria growth. To determine if antibiotic residues remain in the distillers grain (DG) byproduct, which is used as an animal food ingredient, the U.S. Food and Drug Administration/Center for Veterinary Medicine previously developed an LC-MS/MS method to detect residues of erythromycin A, penicillin G, virginiamycin M1, and virginiamycin S1 in DG to enable regulatory decision-making.
OBJECTIVE
Erythromycin and penicillin G were quantitated using the stable isotope dilution technique with their isotopically labeled compounds, which are considered optimal internal standards (ISTDs) for quantitative mass spectrometry. With the commercial availability of virginiamycin M1-d2 since then, the objectives of this study were to evaluate the feasibility of its use as it is only doubly deuterated, and to incorporate it in the method to enhance method performance.
METHOD
Antibiotic residues were solvent-extracted from DG; the extract was cleaned up by a hexane wash and solid phase extraction (SPE) and analyzed by LC-MS/MS.
RESULTS
We established suitability of virginiamycin M1-d2 as an ISTD and incorporated it in the method. For all analytes, accuracy and precision ranged 90 to 102% and 3.8 to 6.8, respectively.
CONCLUSIONS
We modified a previously developed LC-MS/MS method that uses virginiamycin M1-d2 as an ISTD to support surveillance studies to determine several drugs in DG.
HIGHLIGHTS
Virginiamycin M1-d2 was successfully incorporated into the method for better virginiamycin M1 quantitation. This addition also allowed calibration curves for all analytes to be constructed in solvent, thereby simplifying the method.
Topics: Animals; Anti-Bacterial Agents; Streptogramin A; Chromatography, Liquid; Tandem Mass Spectrometry; Penicillin G; Erythromycin; Solvents; Edible Grain; Solid Phase Extraction; Drug Residues
PubMed: 36975613
DOI: 10.1093/jaoacint/qsad032 -
Journal of Biological Inorganic... Dec 2022Determination of the toxicity of compounds toward cancer cells is a frequent procedure in drug discovery. For metal complexes, which are often reactive prodrugs, care...
Determination of the toxicity of compounds toward cancer cells is a frequent procedure in drug discovery. For metal complexes, which are often reactive prodrugs, care has to be taken to consider reactions with components of the cell culture medium that might change the speciation of the metal complex before it is taken up by the cells. Here, we consider possible reactions between the clinical platinum drugs cisplatin and oxaliplatin with penicillin G, an antibiotic added routinely to cell culture media to prevent bacterial contamination. Platinum has a high affinity for ligands with sulfur donors. Penicillin G is an unstable thioether that degrades in a range of pathways. Nuclear magnetic resonance (NMR) and UV-Vis absorption spectroscopic studies show that reactions with cisplatin can occur within minutes to hours at 310 K, but more slowly with oxaliplatin. The identities of the Pt- adducts were investigated by mass spectrometry. The marked effect on cytotoxicity of co-incubation of cisplatin with penicillin G was demonstrated for the HeLa human cervical cancer cell line. These studies highlight the possibility that reactions with penicillin G might influence the cytotoxic activity of metal complexes determined in culture media.
Topics: Humans; Cisplatin; Oxaliplatin; Platinum; Coordination Complexes; Organoplatinum Compounds; Antineoplastic Agents; Penicillin G
PubMed: 36153767
DOI: 10.1007/s00775-022-01958-z -
JAAPA : Official Journal of the... Aug 2020Syphilis is on the rise in every age and ethnicity group across the United States. The rate of congenital syphilis has started to rise as well, increasing the need for... (Review)
Review
Syphilis is on the rise in every age and ethnicity group across the United States. The rate of congenital syphilis has started to rise as well, increasing the need for syphilis screening before pregnancy occurs. Raising awareness for syphilis screening, especially among sexually active women, is important, as the implications of this disease have lifelong effects for mother and child.
Topics: Adolescent; Adult; Antitreponemal Agents; Female; Humans; Male; Mass Screening; Penicillin G; Penicillin G Benzathine; Pregnancy; Pregnancy Complications, Infectious; Syphilis; Syphilis Serodiagnosis; Syphilis, Congenital; Treponema pallidum; Young Adult
PubMed: 32740114
DOI: 10.1097/01.JAA.0000668824.69965.c8 -
European Review For Medical and... Aug 2023The aim of our study is to determine the uropathogenic causing urinary tract infections (UTIs) and their incidences, assess their antibiotic resistance, and determine an...
OBJECTIVE
The aim of our study is to determine the uropathogenic causing urinary tract infections (UTIs) and their incidences, assess their antibiotic resistance, and determine an appropriate empirical antibiotic treatment strategy.
PATIENTS AND METHODS
We retrospectively analyzed the culture and antibiogram results of urine cultures of 49,706 patients aged 1 day to 18 years who applied to Diyarbakır Children's Hospital between March 2018 and October 2022.
RESULTS
A total of 4,064 cases meeting the study criteria were recorded. Girls comprised 76.7% of the study population. While reproduction in urine culture was more common in boys in the 0-1 age group, there was a decrease in the number of boys with increasing age, and the most common culture growth was seen in girls in the 5-10 age group (p<0.001). Escherichia coli (E. coli) infections were more common in girls, while non-E. coli infections were more common in boys (p<0.001). Gram-negative bacterial growth in urine cultures was the most common growth type. In descending order, E. coli was grown in 68.1% of all cultures, Klebsiella spp in 12.6%, and Proteus spp in 3.9%. Less commonly, Pseudomonas spp (2.8%), Enterobacter spp (1.5%), and fungi (1.1%) were grown. Antibiotic resistance/sensitivity tests revealed resistance patterns most commonly against ampicillin (73.2%), amoxicillin-clavulanate (57.9%), cefuroxime axetil (46.7%), cefixime (51%), and ceftriaxone (40.5%), and less commonly against meropenem (1.7%), amikacin (2.4%), and nitrofurantoin (9.8%). Escherichia coli showed resistance most commonly against ampicillin (69.8%), amoxicillin-clavulanate (59.7%), and cefixime (51.3%), while non-E.coli bacteria showed resistance most commonly against ampicillin (84.6%), amoxicillin (52.0%), and cefixime (50%). Resistance against nitrofurantoin was lower in E. coli infections than non-E. coli infections, although the difference did not reach statistical significance (3.7% and 27%, respectively; p=0.149). In contrast, resistance against trimethoprim-sulfamethoxazole was more common in E. coli infections than non-E. coli infections, although the difference was not statistically significant (42% and 29.7%, respectively; p=0.093).
CONCLUSIONS
Our study revealed that resistance has developed at very high rates against many oral and parenteral antibiotics that we use in the treatment of UTIs. If our rate of antibiotic use continues to increase this way, it is predicted that UTIs will, unfortunately, become untreatable with oral antibiotics. This upsetting point reached by our country, which is the state that uses antibiotics the most in Europe, exemplifies the importance of rational antibiotic use for the whole world.
Topics: Male; Female; Humans; Child; Infant, Newborn; Infant; Child, Preschool; Anti-Bacterial Agents; Cefixime; Nitrofurantoin; Retrospective Studies; Urinary Tract Infections; Ampicillin; Amoxicillin; Drug Resistance, Microbial; Amoxicillin-Potassium Clavulanate Combination; Escherichia coli
PubMed: 37667945
DOI: 10.26355/eurrev_202308_33421