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Clinical Pharmacokinetics Apr 2023The pharmacokinetic variability of ampicillin-sulbactam in adults has not been extensively described, particularly in patients with a reduced renal function (i.e.,...
BACKGROUND
The pharmacokinetic variability of ampicillin-sulbactam in adults has not been extensively described, particularly in patients with a reduced renal function (i.e., < 60 mL/min).
OBJECTIVE
This study investigated the population pharmacokinetics of ampicillin and sulbactam in patients with a wide range of renal functions and sought to define dosing approaches that have a high likelihood for optimising drug exposure.
METHODS
Serial blood samples were collected from 16 adult patients receiving intravenous ampicillin-sulbactam in general wards. Total ampicillin and sulbactam concentrations were measured by chromatographic assay and pharmacokinetic parameters were estimated using Pmetrics. Monte Carlo simulations were used to evaluate the probability of target attainment (PTA) of free ampicillin and sulbactam concentrations exceeding the minimum inhibitory concentration (MIC) for 60% and 100% of the dosing interval. Fractional target attainment (FTA) was calculated against MIC distributions of common hospital pathogens. A threshold of ≥ 90% and ≥ 95% was used to define both optimal PTA and FTA, respectively.
RESULTS
The median (range) age, weight, and serum creatinine of the study population was 68 (40-82) years, 62 (40-82) kg, and 1.4 (0.6-6.4) mg/dL, respectively. The pharmacokinetics of ampicillin and sulbactam were best described by a two-compartment model with serum creatinine most closely associated with clearance for both drugs. The estimated ampicillin and sulbactam clearances were 5.58 L/h and 4.79 L/h, respectively, while the volumes of distribution were 12.6 L and 15.36 L, respectively. Approved dosing regimens of ampicillin-sulbactam were sufficient against MICs ≤ 8 and ≤ 4 mg/L, respectively. A 4-h infusion enabled optimal PTA at higher MICs. For both dosing targets, optimal FTAs were obtained against Streptococcus pneumoniae.
CONCLUSION
Optimal FTAs were obtained against the susceptible MIC distributions of Escherichia coli, Klebsiella pneumoniae, and Acinetobacter baumannii. Applying a 4-h infusion will enhance PTA and FTA, particularly at higher MICs.
Topics: Humans; Adult; Aged; Aged, 80 and over; Sulbactam; Anti-Bacterial Agents; Creatinine; Ampicillin; Microbial Sensitivity Tests
PubMed: 36853585
DOI: 10.1007/s40262-023-01219-5 -
PloS One 2023Streptococcal toxic shock syndrome (STSS) is a severe consequence of infections from Streptococcus pyogenes. The early identification and timely intervention with...
INTRODUCTION
Streptococcal toxic shock syndrome (STSS) is a severe consequence of infections from Streptococcus pyogenes. The early identification and timely intervention with appropriate anti-infective agents are pivotal for managing pediatric STSS. This study evaluates the effectiveness of various treatment regimens for STSS in children.
METHODS
Clinical data of children with STSS resulting from β-hemolytic streptococcal infections in two hospitals were retrospectively analyzed from January 2009 to April 2023. Additionally, literature from the China National Knowledge Infrastructure on pediatric STSS was examined. Antimicrobial treatments were categorized into four groups based on their compositions, with an additional categorization for adjunct therapeutic drugs.
RESULTS
Of 32 confirmed STSS cases, all displayed sensitivity to ampicillin, β-lactam antibiotics, and vancomycin, but resistance to clindamycin, erythromycin, and tetracycline. From the literature, 23 studies with 50 cases were extracted, leading to a total of 82 patients for evaluation. The efficacy rates varied significantly among the four treatment groups. Notably, the standard penicillin-containing group exhibited the highest efficacy (86.4%), while the group with macrolides/unused antibiotics registered a 0% efficacy rate. The other two groups demonstrated efficacy rates of 32.1% and 42.3%.
CONCLUSION
For pediatric STSS, Streptococcus pyogenes shows notable sensitivity to ampicillin. Implementing timely β-lactam antibiotics, specifically penicillin, in conjunction with clindamycin and intravenous immunoglobulins enhances the treatment success rate.
Topics: Humans; Child; Anti-Bacterial Agents; Clindamycin; Shock, Septic; Retrospective Studies; Streptococcal Infections; Streptococcus pyogenes; Penicillins; Ampicillin; Protein Synthesis Inhibitors; Macrolides
PubMed: 37824534
DOI: 10.1371/journal.pone.0292311 -
Clinical Oral Investigations Dec 2022Mechanisms of wound healing are often impaired in patients with osteonecrosis of the jaw (ONJ). According to the guidelines for the treatment of this disease, early...
OBJECTIVES
Mechanisms of wound healing are often impaired in patients with osteonecrosis of the jaw (ONJ). According to the guidelines for the treatment of this disease, early surgical intervention is indicated. However, surgery often faces complications such as wound healing disorders. The application of platelet-rich fibrin (PRF) after necrosectomy between bone and mucosa may constitute a promising approach to improve surgical results. An aspect that was not investigated until now is that PRF acts as a "bio-carrier" for antibiotics previously applied intravenously.
MATERIALS AND METHODS
We investigated the antimicrobial properties of PRF in 24 patients presenting ONJ undergoing systemic antibiosis with ampicillin/sulbactam. We measured the concentration of ampicillin/sulbactam in plasma and PRF and performed agar diffusion tests. Ampicillin/sulbactam was applied intravenously to the patient 10 minutes for blood sampling for PRF. No further incorporation of patients' blood or PRF product with antibiotic drugs was obtained. Four healthy patients served as controls.
RESULTS
Our results revealed that PRF is highly enriched with ampicillin/sulbactam that is released to the environment. The antibiotic concentration in PRF was comparable to the plasma concentration of ampicillin/sulbactam. The inhibition zone (IZ) of PRF was comparable to the standard ampicillin/sulbactam discs used in sensitivity testing.
CONCLUSIONS
The results of our study demonstrated that PRF is a reliable bio-carrier for systemic applied antibiotics and exhibits a large antimicrobial effect.
CLINICAL RELEVANCE
We describe a clinically useful feature of PRF as a bio-carrier for antibiotics. Especially when applied to poorly perfused tissues and bone such as in ONJ, the local release of antibiotics can reduce wound healing disorders like infections.
Topics: Humans; Platelet-Rich Fibrin; Sulbactam; Ampicillin; Anti-Bacterial Agents
PubMed: 35941396
DOI: 10.1007/s00784-022-04663-y -
European Journal of Clinical... Aug 2019Staphylococcus lugdunensis is a coagulase-negative staphylococcus (CoNS) with unusual pathogenicity resembling that of S. aureus. Unlike other CoNS, S. lugdunensis...
Staphylococcus lugdunensis is a coagulase-negative staphylococcus (CoNS) with unusual pathogenicity resembling that of S. aureus. Unlike other CoNS, S. lugdunensis remains susceptible to most antibiotics. The resistance to penicillin varies widely (range, 15-87% worldwide), whereas methicillin resistance is still rare. We aimed to evaluate treatment options for infections caused by S. lugdunensis and more specifically to investigate whether penicillin G could be a better treatment choice than oxacillin. Susceptibility testing was performed using the disc diffusion method for penicillin G, cefoxitin, trimethoprim/sulfamethoxazole, erythromycin, clindamycin, gentamicin, norfloxacin, fusidic acid, rifampicin, and fosfomycin. Isolates susceptible to penicillin G were further tested with a gradient test for penicillin G and oxacillin. Of the 540 clinical isolates tested, 74.6% were susceptible to penicillin G. Among these penicillin-susceptible isolates, the MIC and MIC values for penicillin G were threefold lower than that for oxacillin. A majority of the isolates were susceptible to all other antibiotics tested. Breakpoints for fosfomycin have not yet been defined, and so no conclusions could be drawn. Two isolates were resistant to cefoxitin and carried the mecA gene; whole-genome sequencing revealed that both harbored the SCCmec element type IVa(2B). S. lugdunensis isolated in Sweden were susceptible to most tested antibiotics. Penicillin G may be a more optimal treatment choice than oxacillin. Although carriage of the mecA gene is rare among S. lugdunensis, it does occur.
Topics: Anti-Bacterial Agents; Bacterial Proteins; Disk Diffusion Antimicrobial Tests; Drug Resistance, Bacterial; Oxacillin; Penicillin G; Staphylococcus lugdunensis; Sweden; Whole Genome Sequencing
PubMed: 31144243
DOI: 10.1007/s10096-019-03571-6 -
Journal of Gastrointestinal and Liver... Jun 2017
Topics: Amoxicillin; Anti-Bacterial Agents; Drug Therapy, Combination; Helicobacter Infections; Helicobacter pylori; Humans
PubMed: 28617879
DOI: 10.15403/jgld.2014.1121.262.hpy -
Revista Medica de Chile Mar 2021National rates of HIV, gonorrhoeae and syphilis have increased in Chile in recent years, but it is not known if syphilis among pregnant women (PW) is also escalating.
BACKGROUND
National rates of HIV, gonorrhoeae and syphilis have increased in Chile in recent years, but it is not known if syphilis among pregnant women (PW) is also escalating.
AIM
To explore syphilis rates among PW in a southern Chilean region and to describe clinical features of mothers and offspring.
PATIENTS AND METHODS
We selected PW with positive VDRL or T. pallidum micro-he-magglutination (MHA-TP) reactive tests, referred to a high-risk obstetrical pathology center between 2011 and 2019. Clinical information of mothers and their offspring was obtained from their medical records.
RESULTS
Syphilis rates among PW increased from 0.4 to 7.2 per 1,000 live births in the reference center from 2013 to 2019, along with a national and regional increase in both sexes. Twenty-nine cases of PW with syphilis were identified with a median age of 28 years (interquartile range 23-32). Seventeen percent had a history of drug abuse, and 14% had previous sexually transmitted diseases. In seven cases (24%), the diagnosis occurred at delivery. Three percent of patients had a primary syphilis, 14% a secondary syphilis, 24% an early latent syphilis, and 59% a latent syphilis. All cases except one case were treated with benzathine penicillin G and the remaining with erythromycin due to allergy suspicion. Penicillin desensitization was required in two cases (7%). Treatment timing was inadequate in 10 cases (34.5%). Of 19 patients with available serological follow-up, 10 (53%) showed a significant decrease in VDRL titers (≥ 2 dilutions) and two cases had re-infection. Two patients (7%) had an abortion, two had congenital syphilis (7%), and six had premature births (21%), totaling 35% of adverse-pregnancy outcomes.
CONCLUSIONS
Resurgence of syphilis among pregnant women is happening in southern Chile and is associated to adverse-pregnancy outcomes.
Topics: Adult; Chile; Female; Humans; Male; Penicillin G Benzathine; Pregnancy; Pregnancy Complications, Infectious; Pregnant Women; Syphilis; Syphilis, Congenital
PubMed: 34479313
DOI: 10.4067/s0034-98872021000300348 -
Molecules (Basel, Switzerland) Jun 2023Copper (Cu) is an essential trace metal and its concentration in body plasma is tightly regulated. An increase in Cu concentration in body fluids is observed in numerous... (Review)
Review
Copper (Cu) is an essential trace metal and its concentration in body plasma is tightly regulated. An increase in Cu concentration in body fluids is observed in numerous pathological conditions, including infections caused by microorganisms. Evidence shows that Cu ions can impact the activity of antibiotics by increasing efficiency or diminishing/neutralizing antibiotic activity, forming complexes which may lead to antibiotic structure degradation. Herein, we represent the evidence available on Cu-antibiotic interactions and their possible impact on antimicrobial therapy efficiency. So far, in vitro studies described interactions between Cu ions and the majority of antibiotics in clinical use: penicillins, cephalosporins, carbapenems, macrolides, aminoglycosides, tetracyclines, fluoroquinolones, isoniazid, metronidazole. In vitro-described degradation or lower antimicrobial activity of amoxicillin, ampicillin, cefaclor, ceftriaxone, and meropenem in the presence of Cu ions suggest caution when using prescribed antibiotics in patients with altered Cu levels. On the other hand, several Cu-dependent compounds with antibacterial activity including the drug-resistant bacteria were discovered, such as thiosemicarbazones, disulfiram, dithiocarbamates, 8-hydroxiquinoline, phenanthrolines, pyrithione. Having in mind that the development of new antibiotics is already marked as inadequate and does not meet global needs, the potential of Cu-antibiotic interactions to change the efficiency of antimicrobial therapy requires further investigation.
Topics: Humans; Copper; Anti-Bacterial Agents; Meropenem; Ampicillin; Ions
PubMed: 37446795
DOI: 10.3390/molecules28135133 -
The Pediatric Infectious Disease Journal Dec 2022This study aimed to evaluate antibiotic prescriptions for children with otitis media (OM) in a large nationwide network of private clinics between 2014 and 2020. Special...
AIM
This study aimed to evaluate antibiotic prescriptions for children with otitis media (OM) in a large nationwide network of private clinics between 2014 and 2020. Special focus was paid to amoxicillin and amoxicillin-clavulanic acid prescriptions, which the national guidelines recommend for first-line drugs. We also focused on macrolides, which are commonly prescribed for respiratory tract infections in children but are not appropriate for OM cases.
METHODS
The data were obtained from the electronic health records of about 250,000 annual visits in <18 years old children. The collected variables were all diagnoses, age, visit year, doctor's specialty, and prescribed antibiotics. Children with OM and upper respiratory tract infections were included, but those with lower respiratory tract infections were excluded.
RESULTS
The number of children with OM was 357,390 (55.2% boys). Antibiotics were prescribed in 44.8% of cases, with the lowest proportion (44.1%) being in <2 years old children. The overall prescription rate decreased from 48.3% in 2014 to 41.4% in 2020. The rates were 19.3% and 18.1% for amoxicillin and 12.6% and 13.2% for amoxicillin-clavulanic acid, respectively. Macrolide prescriptions were reduced from 7.5% to 3.5%. Pediatricians prescribed antibiotics for 38.8%, general practitioners for 54.0% and ear, nose and throat physicians for 39.8% of children with OM.
CONCLUSION
The selection of antibiotics for OM, when prescribed, was according to the recommendations (amoxicillin or amoxicillin-clavulanic acid) in 80.1% of pediatricians, 67.0% of general practitioners and 55.1% of ear, nose and throat physicians.
Topics: Child; Male; Humans; Adolescent; Child, Preschool; Female; Anti-Bacterial Agents; Amoxicillin-Potassium Clavulanate Combination; Drug Utilization; Outpatients; Practice Patterns, Physicians'; Otitis Media; Amoxicillin; Respiratory Tract Infections; Macrolides
PubMed: 36102742
DOI: 10.1097/INF.0000000000003693 -
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 Journal of Antimicrobial... Nov 2022
Topics: Infant; Infant, Newborn; Humans; Mezlocillin; Bacterial Infections; Kinetics
PubMed: 36101504
DOI: 10.1093/jac/dkac305