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Therapeutic Drug Monitoring Oct 2023Recently, several studies have assessed the effects of therapeutic drug monitoring of frequently prescribed beta-lactam antibiotics, for which they were quantified in...
BACKGROUND
Recently, several studies have assessed the effects of therapeutic drug monitoring of frequently prescribed beta-lactam antibiotics, for which they were quantified in human plasma samples. Beta-lactams are considered unstable, leading to extra challenges in quantification. Therefore, to ensure sample stability and minimize sample degradation before analysis, stability studies are crucial. This study investigated the stability of 10 frequently used beta-lactam antibiotics in human plasma at relevant storage conditions for clinical use.
METHODS
Amoxicillin, benzylpenicillin, cefotaxime, ceftazidime, ceftriaxone, cefuroxime, flucloxacillin, imipenem, meropenem, and piperacillin were analyzed using ultraperformance convergence chromatography tandem mass spectrometry and liquid chromatography tandem mass spectrometry. Their short-term and long-term stabilities were investigated by measuring quality control samples at low and high concentrations against freshly prepared calibration standards. Measured concentrations at each time point were compared with the concentrations at T = 0. Antibiotics were considered stable if recovery results were between 85% and 115%.
RESULTS
Short-term stability results indicated ceftriaxone, cefuroxime, and meropenem to be stable up to 24 hours at room temperature. All evaluated antibiotics, except imipenem, were stable on ice in a cool box for 24 hours. Amoxicillin, benzylpenicillin, and piperacillin were stable for 24 hours at 4-6°C. Cefotaxime, ceftazidime, cefuroxime, and meropenem were stable at 4-6°C up to 72 hours. Ceftriaxone and flucloxacillin were stable for 1 week at 4-6°C. Long-term stability results showed that all antibiotics were stable up to 1 year at -80°C, except imipenem and piperacillin, which were stable for 6 months at -80°C.
CONCLUSIONS
Plasma samples for amoxicillin, benzylpenicillin, cefotaxime, ceftazidime, flucloxacillin, and piperacillin may be stored for a maximum of 24 hours in a cool box. Refrigeration is suitable for plasma samples of amoxicillin, benzylpenicillin, meropenem, and piperacillin for up to 24 hours and cefotaxime, ceftriaxone, ceftazidime and cefuroxime for 72 hours. Plasma samples for imipenem should be frozen directly at -80°C. For long-term storage, plasma samples can be stored at -80°C for a maximum of 6 months for imipenem and piperacillin and 12 months for all other evaluated antibiotics.
Topics: Humans; Meropenem; Ceftazidime; Floxacillin; Cefuroxime; Ceftriaxone; Anti-Bacterial Agents; Piperacillin; Monobactams; Tandem Mass Spectrometry; Imipenem; Cefotaxime; Amoxicillin
PubMed: 37199408
DOI: 10.1097/FTD.0000000000001100 -
World Journal of Gastroenterology Nov 2021Therapy of () requires a combination of antibiotics together with an acid suppressing agent; most treatment regimens include Amoxicillin as one of the antibiotics,... (Review)
Review
Therapy of () requires a combination of antibiotics together with an acid suppressing agent; most treatment regimens include Amoxicillin as one of the antibiotics, which is an important constituent as resistance to it is low. However, allergies to the penicillin group of antibiotics are not uncommon, and treating infection in such individuals can be challenging due to the restricted choice of regimens. The aim of this review is to summarise the evidence for therapeutic options in patients with infection and penicillin allergy. A literature search was conducted in PubMed for English language publications using the key words 'Helicobacter' and 'treatment' or 'therapy' and 'penicillin' or 'beta-lactam' and 'allergy' or 'anaphylaxis'. Eighteen studies were identified that specifically evaluated treatment success in penicillin allergic patients. The number of subjects in most of them was low and many were retrospective, uncontrolled, single cohort studies. The most effective option for first-line treatment appears to be Bismuth-based quadruple therapy for 10-14 d. The evidence supports second-line treatment with Levoflaxacin-based triple therapy for 10 d. Patients with persistent infection after 2 treatment courses should be considered for testing to confirm penicillin allergy. Further treatment should be guided by the results of culture and sensitivity testing.
Topics: Amoxicillin; Anti-Bacterial Agents; Bismuth; Drug Hypersensitivity; Drug Therapy, Combination; Helicobacter Infections; Helicobacter pylori; Humans; Metronidazole; Penicillins; Proton Pump Inhibitors; Retrospective Studies; Treatment Outcome
PubMed: 34908805
DOI: 10.3748/wjg.v27.i44.7661 -
Microbiology Spectrum Aug 2022Penicillin plus ceftriaxone is a promising alternative to ampicillin plus ceftriaxone for the treatment of Enterococcus faecalis infective endocarditis. Limited data is...
Penicillin plus ceftriaxone is a promising alternative to ampicillin plus ceftriaxone for the treatment of Enterococcus faecalis infective endocarditis. Limited data is available supporting the utilization of penicillin plus ceftriaxone. A total of 20 E. faecalis isolates; one wild-type strain (JH2-2) and 19 clinical blood strains were assessed for penicillin plus ceftriaxone and ampicillin plus ceftriaxone synergy using a 24-h time-kill experiment. Susceptibility was determined by broth microdilution. Differences in bactericidal, bacteriostatic, or inactivity, as well as synergy between treatments were assessed by chi-square or Fisher exact test. All E. faecalis isolates were considered susceptible to ampicillin and penicillin. Ampicillin plus ceftriaxone versus penicillin plus ceftriaxone similarly demonstrated synergy. Bactericidal activity was more commonly observed for ampicillin plus ceftriaxone versus penicillin plus ceftriaxone. Among isolates with a penicillin MIC of 4 μg/mL ( = 7), synergistic activity for both combinations was less common compared to isolates with a penicillin MIC ≤ 2 μg/mL ( = 13). Ampicillin plus ceftriaxone and penicillin plus ceftriaxone demonstrate similar synergistic potential against E. faecalis clinical blood isolates, but strains with higher penicillin and ceftriaxone MICs less frequently demonstrated synergy. Further research is warranted to determine the role of the penicillin plus ceftriaxone therapy and the penicillin MIC in clinical practice. Penicillin plus ceftriaxone demonstrates similar synergistic activity against to ampicillin plus ceftriaxone. Isolates with a penicillin MIC of 4 mg/L and a ceftriaxone MIC of 512 or higher, lack penicillin plus ceftriaxone synergy despite the penicillin susceptibility MIC breakpoint of 8 mg/L.
Topics: Ampicillin; Anti-Bacterial Agents; Ceftriaxone; Drug Synergism; Drug Therapy, Combination; Enterococcus faecalis; Microbial Sensitivity Tests; Penicillins
PubMed: 35703558
DOI: 10.1128/spectrum.00621-22 -
Scientific Reports Aug 2020Immediate hypersensitivity reaction (IHR) can be divided into allergic- and non-allergic-mediated, while "anaphylaxis" is reserved for severe IHR. Clinically, true...
Immediate hypersensitivity reaction (IHR) can be divided into allergic- and non-allergic-mediated, while "anaphylaxis" is reserved for severe IHR. Clinically, true penicillin allergy is rare and most reported penicillin allergy is "spurious". Penicillin-initiated anaphylaxis is possible to occur in skin test- and specific IgE-negative patients. The contact system is a plasma protease cascade initiated by activation of factor XII (FXII). Many agents with negative ion surface can activate FXII to drive contact system. Our data showed that penicillin significantly induced hypothermia in propranolol- or pertussis toxin-pretreated mice. It also caused a rapid and reversible drop in rat blood pressure, which did not overlap with IgE-mediated hypotension. These effects could be countered by a bradykinin-B2 receptor antagonist icatibant, and consistently, penicillin indeed increased rat plasma bradykinin. Moreover, penicillin not only directly activated contact system FXII-dependently, but also promoted bradykinin release in plasma incubated-human umbilical vein endothelial cells. In fact, besides penicillin, other beta-lactams also activated the contact system in vitro. Since the autoactivation of FXII can be affected by multiple-factors, plasma from different healthy individuals showed vastly different amidolytic activity in response to penicillin, suggesting the necessity of determining the potency of penicillin to induce individual plasma FXII activation. These results clarify that penicillin-initiated non-allergic anaphylaxis is attributed to contact system activation, which might bring more effective diagnosis options for predicting penicillin-induced fatal risk and avoiding costly and inappropriate treatment clinically.
Topics: Anaphylaxis; Animals; Blood Coagulation; Bradykinin; Bradykinin Receptor Antagonists; Capillary Permeability; Enzyme Activation; Factor XIIa; Human Umbilical Vein Endothelial Cells; Humans; Hypothermia; Kallikrein-Kinin System; Male; Mice; Mice, Inbred BALB C; Penicillin G; Pertussis Toxin; Propranolol; Rats; Rats, Sprague-Dawley; Receptor, Bradykinin B2; beta-Lactams
PubMed: 32843685
DOI: 10.1038/s41598-020-71083-x -
Journal of Microbiology and... Apr 2024is a commonly used probiotic, and many researchers have focused on its stress response to improve its functionality and survival. However, studies on persister cells,...
is a commonly used probiotic, and many researchers have focused on its stress response to improve its functionality and survival. However, studies on persister cells, dormant cells that aid bacteria in surviving general stress, have focused on pathogenic bacteria that cause infection, not . Thus, understanding persister cells will provide essential clues for understanding how survives and maintains its function under various environmental conditions. We treated strains with various antibiotics to determine the conditions required for persister formation using kill curves and transmission electron microscopy. In addition, we observed the resuscitation patterns of persister cells using single-cell analysis. Our results show that creates a small population of persister cells (0.0001-1% of the bacterial population) in response to beta-lactam antibiotics such as ampicillin and amoxicillin. Moreover, only around 0.5-1% of persister cells are heterogeneously resuscitated by adding fresh media; the characteristics are typical of persister cells. This study provides a method for forming and verifying the persistence of and demonstrates that antibiotic-induced persister cells show characteristics of dormancy, sensitivity of antibiotics, same as exponential cells, multi-drug tolerance, and resuscitation, which are characteristics of general persister cells. This study suggests that the mechanisms of formation and resuscitation may vary depending on the characteristics, such as the membrane structure of the bacterial species.
Topics: Anti-Bacterial Agents; Lactobacillus; Ampicillin; Microbial Viability; Microbial Sensitivity Tests; Microscopy, Electron, Transmission; Probiotics; Amoxicillin
PubMed: 38326923
DOI: 10.4014/jmb.2312.12035 -
Antimicrobial Agents and Chemotherapy May 2018Group B streptococci are common causative agents of early-onset neonatal sepsis (EOS). Pharmacokinetic (PK) data for penicillin G have been described for extremely...
Group B streptococci are common causative agents of early-onset neonatal sepsis (EOS). Pharmacokinetic (PK) data for penicillin G have been described for extremely preterm neonates but have been poorly described for late-preterm and term neonates. Thus, evidence-based dosing recommendations are lacking. We describe the PK of penicillin G in neonates with a gestational age (GA) of ≥32 weeks and a postnatal age of <72 h. Penicillin G was administered intravenously at a dose of 25,000 or 50,000 IU/kg of body weight every 12 h (q12h). At steady state, PK blood samples were collected prior to and at 5 min, 1 h, 3 h, 8 h, and 12 h after injection. Noncompartmental PK analysis was performed with WinNonlin software. With those data in combination with data from neonates with a GA of ≤28 weeks, we developed a population PK model using NONMEM software and performed probability of target attainment (PTA) simulations. In total, 16 neonates with a GA of ≥32 weeks were included in noncompartmental analysis. The median volume of distribution () was 0.50 liters/kg (interquartile range, 0.42 to 0.57 liters/kg), the median clearance (CL) was 0.21 liters/h (interquartile range, 0.16 to 0.29 liters/kg), and the median half-life was 3.6 h (interquartile range, 3.2 to 4.3 h). In the population PK analysis that included 35 neonates, a two-compartment model best described the data. The final parameter estimates were 10.3 liters/70 kg and 29.8 liters/70 kg for of the central and peripheral compartments, respectively, and 13.2 liters/h/70 kg for CL. Considering the fraction of unbound penicillin G to be 40%, the PTA of an unbound drug concentration that exceeds the MIC for 40% of the dosing interval was >90% for MICs of ≤2 mg/liter with doses of 25,000 IU/kg q12h. In neonates, regardless of GA, the PK parameters of penicillin G were similar. The dose of 25,000 IU/kg q12h is suggested for treatment of group B streptococcal EOS diagnosed within the first 72 h of life. (This study was registered with the EU Clinical Trials Register under EudraCT number 2012-002836-97.).
Topics: Anti-Bacterial Agents; Female; Gestational Age; Humans; Infant, Newborn; Infant, Premature; Male; Microbial Sensitivity Tests; Monte Carlo Method; Penicillin G; Streptococcus
PubMed: 29463540
DOI: 10.1128/AAC.02238-17 -
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 -
The Journal of Infectious Diseases Jun 2022Historically, antimicrobial resistance has been rare in US invasive meningococcal disease cases.
BACKGROUND
Historically, antimicrobial resistance has been rare in US invasive meningococcal disease cases.
METHODS
Meningococcal isolates (n = 695) were collected through population-based surveillance, 2012-2016, and national surveillance, 2015-2016. Antimicrobial susceptibility was assessed by broth microdilution. Resistance mechanisms were characterized using whole-genome sequencing.
RESULTS
All isolates were susceptible to 6 antibiotics (cefotaxime, ceftriaxone, meropenem, rifampin, minocycline, and azithromycin). Approximately 25% were penicillin or ampicillin intermediate; among these, 79% contained mosaic penA gene mutations. Less than 1% of isolates were penicillin, ampicillin, ciprofloxacin, or levofloxacin resistant.
CONCLUSIONS
Penicillin- and ampicillin-intermediate isolates were common, but resistance to clinically relevant antibiotics remained rare.
Topics: Ampicillin; Anti-Bacterial Agents; Ceftriaxone; Ciprofloxacin; Humans; Meningococcal Infections; Microbial Sensitivity Tests; Neisseria meningitidis; Penicillins; United States
PubMed: 35266516
DOI: 10.1093/infdis/jiac046 -
Hospital Pediatrics Apr 2023Penicillin (PCN) allergy labels are widely recognized to be highly inaccurate. Little is known about parental perceptions of the PCN allergy evaluation and removal...
BACKGROUND
Penicillin (PCN) allergy labels are widely recognized to be highly inaccurate. Little is known about parental perceptions of the PCN allergy evaluation and removal process, especially in the hospital setting.
METHODS
Focus groups were held with parents of children and adolescents with a PCN allergy label discharged from a large academic children's hospital between January 1, 2019, and April 15, 2020. The open-ended, semistructured moderator guide included questions about PCN allergy testing and evaluation, accuracy of the PCN allergy diagnosis, amoxicillin oral challenges, delabeling process, and preferred setting for PCN allergy delabeling evaluation (outpatient clinic, hospital, etc). Study investigators coded the transcripts and identified underlying themes using inductive and deductive thematic analysis.
RESULTS
A total of 21 parents and 2 adolescents participated across 4 focus groups. We developed a theoretical framework depicting key elements of parents' and adolescents' experiences with PCN allergies, consisting of 4 major interconnected themes: (1) family context; (2) the invitation to delabel; (3) decision context; and (4) the PCN delabeling outcome. PCN allergies remained a concern for families even if their children passed an oral challenge. Some parents preferred testing to be performed in the hospital and felt this was a safer location for the procedure.
CONCLUSIONS
Parents are amenable to hospital based PCN allergy evaluation and delabeling. Further studies should incorporate parental and patient preferences to implement safe and effective PCN allergy delabeling processes in the hospital setting.
Topics: Child; Adolescent; Humans; Penicillins; Drug Hypersensitivity; Amoxicillin; Risk Assessment; Hypersensitivity; Anti-Bacterial Agents
PubMed: 36919441
DOI: 10.1542/hpeds.2022-006737 -
Toxicological Sciences : An Official... Jul 2022Violative chemical residues in edible tissues from food-producing animals are of global public health concern. Great efforts have been made to develop physiologically...
An Interactive Generic Physiologically Based Pharmacokinetic (igPBPK) Modeling Platform to Predict Drug Withdrawal Intervals in Cattle and Swine: A Case Study on Flunixin, Florfenicol, and Penicillin G.
Violative chemical residues in edible tissues from food-producing animals are of global public health concern. Great efforts have been made to develop physiologically based pharmacokinetic (PBPK) models for estimating withdrawal intervals (WDIs) for extralabel prescribed drugs in food animals. Existing models are insufficient to address the food safety concern as these models are either limited to 1 specific drug or difficult to be used by non-modelers. This study aimed to develop a user-friendly generic PBPK platform that can predict tissue residues and estimate WDIs for multiple drugs including flunixin, florfenicol, and penicillin G in cattle and swine. Mechanism-based in silico methods were used to predict tissue/plasma partition coefficients and the models were calibrated and evaluated with pharmacokinetic data from Food Animal Residue Avoidance Databank (FARAD). Results showed that model predictions were, in general, within a 2-fold factor of experimental data for all 3 drugs in both species. Following extralabel administration and respective U.S. FDA-approved tolerances, predicted WDIs for both cattle and swine were close to or slightly longer than FDA-approved label withdrawal times (eg, predicted 8, 28, and 7 days vs labeled 4, 28, and 4 days for flunixin, florfenicol, and penicillin G in cattle, respectively). The final model was converted to a web-based interactive generic PBPK platform. This PBPK platform serves as a user-friendly quantitative tool for real-time predictions of WDIs for flunixin, florfenicol, and penicillin G following FDA-approved label or extralabel use in both cattle and swine, and provides a basis for extrapolating to other drugs and species.
Topics: Animals; Cattle; Clonixin; Drug Residues; Drugs, Generic; Models, Biological; Penicillin G; Swine; Thiamphenicol
PubMed: 35642931
DOI: 10.1093/toxsci/kfac056