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British Journal of Clinical Pharmacology Oct 2022Ductopenia is often regarded as a chronic process where ≥50% of portal tracts lack bile ducts, which is also known as vanishing bile duct syndrome (VBDS). One... (Review)
Review
Ductopenia is often regarded as a chronic process where ≥50% of portal tracts lack bile ducts, which is also known as vanishing bile duct syndrome (VBDS). One aetiology is drug-induced liver injury. Cloxacillin, an antistaphylococcal penicillin, typically causes "bland" cholestasis. We present the first case of cloxacillin-induced acute ductopenia or VBDS and a review of published cloxacillin-induced liver injuries. A 66-year-old woman with no prior liver disease, but known penicillin allergy, was treated for postcarotid angioplasty staphylococcal infection with 6 weeks of cloxacillin. She presented with a 2-week history of weakness and jaundice. Laboratory work-up showed elevated liver enzymes with a cholestatic pattern, hyperbilirubinemia and eosinophilia. She required ICU transfer for hypotension and was started empirically on prednisone. Liver biopsy revealed severe centrilobular cholestasis, mild necroinflammation and ductopenia with epithelial injury, but no ductular reaction. Two months later she was discharged on hydrocortisone and ursodiol with persistently elevated alkaline phosphatase and bilirubin. She was considered for liver transplantation but died of liver failure 4 months later. Four additional articles were found with histopathologic descriptions of cloxacillin-related liver injury. These included portal inflammation, cholestasis and mild necroinflammation. Clinical features were reported in two cases; both had mild symptoms with cholestatic liver enzymes and hyperbilirubinemia. Both patients recovered completely within 10-60 days. Cloxacillin-induced cholestasis can be secondary to acute ductopenia, which can result in worse clinical outcomes than previously described "bland" cholestasis. Liver biopsy is recommended to identify cases with acute VBDS.
Topics: Aged; Bile Ducts; Cholestasis; Cloxacillin; Female; Humans; Hyperbilirubinemia; Liver
PubMed: 35730139
DOI: 10.1111/bcp.15445 -
The Journal of Antimicrobial... May 2021To investigate if the addition of cloxacillin to vancomycin enhances the activity of both monotherapies for treating MSSA and MRSA experimental endocarditis (EE) in...
Effectiveness of vancomycin plus cloxacillin compared with vancomycin, cloxacillin and daptomycin single therapies in the treatment of methicillin-resistant and methicillin-susceptible Staphylococcus aureus in a rabbit model of experimental endocarditis.
OBJECTIVES
To investigate if the addition of cloxacillin to vancomycin enhances the activity of both monotherapies for treating MSSA and MRSA experimental endocarditis (EE) in rabbits.
METHODS
Vancomycin plus cloxacillin was compared with the respective monotherapies and daptomycin. In vitro time-kill studies were performed using standard (105 cfu) and high (108 cfu) inocula of five MRSA, one glycopeptide-intermediate (GISA) and five MSSA strains. One MSSA (MSSA-678) and one MRSA (MRSA-277) strain were selected to be used in the in vivo model. A human-like pharmacokinetics model was applied and the equivalents of cloxacillin 2 g/4 h IV and daptomycin 6 mg/kg/day IV were administered. To optimize vancomycin activity, dosage was adjusted to achieve an AUC/MIC ≥400.
RESULTS
Daptomycin sterilized significantly more vegetations than cloxacillin (13/13, 100% versus 9/15, 60%; P = 0.02) and showed a trend of better activity than vancomycin (10/14, 71%; P = 0.09) and vancomycin plus cloxacillin (10/14, 71%; P = 0.09) against MSSA-678. Addition of cloxacillin to vancomycin (13/15, 87%) was significantly more effective than vancomycin (8/16, 50%; P = 0.05) and showed similar activity to daptomycin (13/18, 72%; P = 0.6) against MRSA-277. In all treatment arms, the bacterial isolates recovered from vegetations were re-tested and showed the same daptomycin susceptibility as the original strains.
CONCLUSIONS
Vancomycin plus cloxacillin proved synergistic and bactericidal activity against MRSA. Daptomycin was the most efficacious option against MSSA and similar to vancomycin plus cloxacillin against MRSA. In settings with high MRSA prevalence, vancomycin plus cloxacillin might be a good alternative for empirical therapy of S. aureus IE.
Topics: Animals; Anti-Bacterial Agents; Cloxacillin; Daptomycin; Endocarditis; Endocarditis, Bacterial; Methicillin; Methicillin Resistance; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Rabbits; Staphylococcus aureus; Vancomycin
PubMed: 33837406
DOI: 10.1093/jac/dkab069 -
PloS One 2019A randomized clinical trial was conducted to assess efficacy of intramammary cloxacillin and ampicillin (CLOXIMM), intramammary cefquinome (CEFIMM), and intramuscular...
A randomized clinical trial was conducted to assess efficacy of intramammary cloxacillin and ampicillin (CLOXIMM), intramammary cefquinome (CEFIMM), and intramuscular cefquinome (CEFIM) to treat Streptococcus agalactiae intramammary infections (Trial 1). Subsequently, two treatment groups were extended to assess whether CLOXIMM was not inferior to CEFIMM (Trial 2). Nine farms were included in the study. Milk samples were collected from all quarters of all lactating cows for microbiological identification of S. agalactiae. Positive cows were randomly allocated into four groups: CLOXIMM, CEFIMM, CEFIM, or negative control (CONTROL). Study outcomes were bacteriological cure at 14 (CURE14), 21 (CURE21), and 14 and 21 (CURE1421) days after treatment onset, and somatic cell count. Logistic regression was used to estimate the odds of cure between each treatment and CONTROL. Non-inferiority analysis was performed considering a one-sided 95% confidence interval (CI) and non-inferiority margins (Δ) of 0.10, 0.15, 0.20, and 0.25. Adjusted S. agalactiae bacteriological cure for CLOXIMM, CEFIMM, CEFIM, and CONTROL was 86, 98, 55, and 25% at day 14; 82, 93, 52, and 0% at day 21; and 82, 92, 40, and 0% at days 14 and 21, respectively. Treatment with CLOXIMM and CEFIMM resulted in greater bacteriological cure rates, as compared with CEFIM or CONTROL, which does not justify the use of CEFIM in S. agalactiae eradication programs. The CURE14 difference between CEFIMM and CLOXIMM was of 12.1 percentage points (95% CI: 0.056-0.184). CLOXIMM was considered not inferior to CEFIMM for Δ = 0.20 or 0.25 and inconclusive for Δ = 0.10 or 0.15. Thus, it should be pondered by veterinarians whether an expected 12.1 (5.6-18.4) percentage points increase in cure rate would justify the use of a fourth-generation cephalosporin, as opposed to a combination of traditional IMM drugs (cloxacillin and ampicillin) to treat S. agalactiae subclinical mastitis.
Topics: Ampicillin; Animals; Cattle; Cell Count; Cephalosporins; Cloxacillin; Dairying; Drug Therapy, Combination; Female; Mastitis, Bovine; Risk Factors; Streptococcus agalactiae; Treatment Outcome
PubMed: 31022270
DOI: 10.1371/journal.pone.0216091 -
British Medical Journal Sep 1971
Topics: Administration, Oral; Adult; Cloxacillin; Convalescence; Erythromycin; Humans; Injections, Intramuscular; Male; Middle Aged; Penicillin G; Penicillins; Pneumonia; Pneumonia, Pneumococcal; Smoking; Staphylococcus; Streptococcus pneumoniae
PubMed: 4399404
DOI: No ID Found -
Drugs in R&D Jun 2016The co-existence of malaria with bacterial infections is common in the tropics, hence the concurrent use of antimalarials and antibiotics. (Comparative Study)
Comparative Study Randomized Controlled Trial
INTRODUCTION
The co-existence of malaria with bacterial infections is common in the tropics, hence the concurrent use of antimalarials and antibiotics.
OBJECTIVE
This study aimed to investigate the effect on pharmacokinetics and antimicrobial activity of co-administration of quinine and combined ampicillin-cloxacillin.
METHODS
In total, 14 healthy adults received single oral doses of ampicillin-cloxacillin combination alone and with quinine in a randomized crossover manner. Urine samples collected at predetermined intervals over 48 h were analysed. The effect of quinine on minimum inhibitory concentrations (MICs) of ampicillin and cloxacillin were determined against Staphylococcus aureus by agar diffusion, agar dilution, and broth dilution.
RESULTS
Quinine significantly reduced the rate and extent of excretion of ampicillin and cloxacillin (p < 0.0002). The total amounts of ampicillin and cloxacillin excreted unchanged (Du(∞)) alone were 217.10 ± 53.82 and 199.0 ± 64.29 mg versus 126.40 ± 50.63 and 135.20 ± 52.24 mg, respectively, with quinine. Respective maximum excretion rates (dDu/dt max) for ampicillin and cloxacillin were 43.55 ± 19.41 and 77.64 ± 29.65 mg/h alone versus 18.01 ± 8.52 and 53.16 ± 20.72 mg/h with quinine. This indicates a significant reduction in Du(∞)and dDu/dt max by 41.78 and 58.65 % for ampicillin and 32.06 and 31.53 % for cloxacillin. Conversely, the disposition of quinine was unaffected by ampicillin-cloxacillin (p > 0.1). The MIC of antibiotics alone versus with quinine, respectively, were 0.11 ± 0.04 and 0.78 ± 0.1 µg/ml for ampicillin, and 0.18 ± 0.1 and 0.92 ± 0.4 µg/ml for cloxacillin, with a five- to sevenfold increase (p > 0.01); indicating a decrease in antimicrobial activity by quinine.
CONCLUSIONS
Quinine therefore, reduced the bioavailability and the antimicrobial activity of ampicillin-cloxacillin upon co-administration, which may have therapeutic implications. Caution is required with the co-administration of these medicines.
Topics: Adolescent; Adult; Ampicillin; Anti-Bacterial Agents; Antimalarials; Biological Availability; Chromatography, High Pressure Liquid; Cloxacillin; Cross-Over Studies; Drug Therapy, Combination; Female; Humans; Male; Nigeria; Quinine; Staphylococcus aureus; Young Adult
PubMed: 27020278
DOI: 10.1007/s40268-016-0128-x -
PloS One 2022Staphylococcus epidermis is one of the most frequent causes of device-associated infections due to biofilm formation. Current reports noted that subinhibitory...
The issue beyond resistance: Methicillin-resistant Staphylococcus epidermidis biofilm formation is induced by subinhibitory concentrations of cloxacillin, cefazolin, and clindamycin.
Staphylococcus epidermis is one of the most frequent causes of device-associated infections due to biofilm formation. Current reports noted that subinhibitory concentrations of antibiotics induce biofilm production in some bacteria. Accordingly, we evaluated the effect of exposure of different subinhibitory concentrations of cloxacillin, cefazolin, clindamycin, and vancomycin on the biofilm formation of methicillin-resistant S. epidermidis (MRSE). Antimicrobial susceptibility testing and minimum inhibitory/bactericidal concentration of antimicrobial agents were determined. MRSE isolates were selected, and their biofilm formation ability was evaluated. The effect of subinhibitory concentrations of cloxacillin, cefazolin, clindamycin, and vancomycin, antibiotics selected among common choices in the clinic, on MRSE biofilm formation was determined by the microtitre method. Besides, the effect of subinhibitory concentrations of cloxacillin, cefazolin, clindamycin, and vancomycin on the expression of the biofilm-associated genes icaA and atlE was evaluated by Reverse-transcription quantitative real-time polymerase chain reaction (RT-qPCR). Antimicrobial susceptibility patterns of MRSE strains showed a high level of resistance as follows: 80%, 53.3%, 33.3%, 33.3%, and 26.6%, for erythromycin, trimethoprim-sulfamethoxazole, tetracycline, clindamycin, and gentamicin, respectively. Besides, 73.3% of S. epidermidis strains were Multidrug-resistant (MDR). Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values were in the range of 0.5 to512 μg/mL and 1 to1024 μg/mL for cloxacillin, 0.125 to256 μg/mL and 1 to512 μg/mL for cefazolin, 0.125 to64 μg/mL and 4 to>1024 μg/mL for clindamycin, and 2 to32 μg/mL and 4 to32 μg/mL for vancomycin, respectively. The findings showed that subinhibitory concentrations of cloxacillin, cefazolin, and clindamycin induce biofilm production in MRSE strains. In particular, the OD values of strains were in the range of 0.09-0.95, 0.05-0.86, and 0.06-1 toward cloxacillin, cefazolin, and clindamycin, respectively. On the other hand, exposure to subinhibitory vancomycin concentrations did not increase the biofilm formation in MRSE strains. The findings also demonstrated that sub-MIC of antibiotics up-regulated biofilm-associated genes. In particular, atlE and icaA were up-regulated 0.062 to 1.16 and 0.078 to 1.48 folds, respectively, for cloxacillin, 0.11 to 0.8, and 0.1 to 1.3 folds for cefazolin, 0.18 to 0.98, and 0.19 to 1.4 folds, respectively, for clindamycin. In contrast, the results showed that sub-MIC of vancomycin did not increase the biofilm-associated genes. These findings overall show that exposure to sub-MIC of traditional antibiotics can cause biofilm induction in MRSE, thereby increasing the survival and persistence on various surfaces that worsen the condition of comorbid infections.
Topics: Humans; Staphylococcus epidermidis; Cefazolin; Clindamycin; Vancomycin; Methicillin-Resistant Staphylococcus aureus; Methicillin Resistance; Cloxacillin; Staphylococcal Infections; Microbial Sensitivity Tests; Anti-Bacterial Agents; Biofilms
PubMed: 36350834
DOI: 10.1371/journal.pone.0277287 -
Clinical Biochemistry 2022The most appropriate renal function estimation equation to predict drug clearance is a matter of debate. In this study, we compare the Modification of Diet in Renal...
The most appropriate renal function estimation equation to predict drug clearance is a matter of debate. In this study, we compare the Modification of Diet in Renal Disease (MDRD), the Chronic Kidney Disease Epidemiology collaboration (CKD-EPI) and the Cockroft-Gault (CG) equations to predict amoxicillin and cloxacillin clearance among hospitalized patients receiving high doses of these antibiotic treatments. This study aimed to compare different equations used to predict amoxicillin and cloxacillin clearance among hospitalized patients receiving amoxicillin or cloxacillin treatments outside the intensive care unit. Data from 128 patients contributing 268 plasma samples was analyzed, and correlations between the equations and the amoxicillin and cloxacillin antibiotic clearance rates were calculated. We found a correlation between antibiotic clearance and all the renal function estimation equations, CG being the best, with a R of 0.35 for amoxicillin and 0.29 for cloxacillin (compared to 0.26 and 0.21 for MDRD and 0.12 and 0.24 for CKD-EPI). CG should be preferentially used as a proxy for amoxicillin and cloxacillin drug clearance, but the use of completely different tools such as therapeutic drug monitoring could help individualize antibiotic dosage.
Topics: Humans; Glomerular Filtration Rate; Amoxicillin; Cloxacillin; Anti-Bacterial Agents; Renal Insufficiency, Chronic; Drug Elimination Routes; Kidney; Creatinine
PubMed: 36108718
DOI: 10.1016/j.clinbiochem.2022.09.003 -
Thorax Nov 1970The history and the clinical and necropsy findings are presented of a patient who died from pyaemia occurring as an opportunistic infection complicating a dissecting...
The history and the clinical and necropsy findings are presented of a patient who died from pyaemia occurring as an opportunistic infection complicating a dissecting aortic aneurysm. The diagnosis was made (and treatment instituted) during life: it rested upon repeated isolation of the organism from tracheal aspirations, a positive blood culture and positive serum precipitin reactions to Debilitating disease along with large doses of antibiotics and corticosteroids provided the conditions necessary for the normally saphrophytic fungi to become pathogenic. As the therapy for aspergillosis is still ineffective, the danger of prescribing large doses of antibiotics together with corticosteroids is stressed.
Topics: Ampicillin; Aortic Aneurysm; Aspergillosis; Aspergillus; Autopsy; Blood; Brain; Bronchi; Chloramphenicol; Cloxacillin; Heart; Humans; Hydrocortisone; Lung; Male; Middle Aged; Precipitin Tests; Trachea
PubMed: 5494678
DOI: 10.1136/thx.25.6.702 -
BMJ Case Reports May 2021Flucloxacillin is a penicillin antibiotic used as first-line treatment for soft tissue infections caused by It is used frequently in the elderly and is an established...
Flucloxacillin is a penicillin antibiotic used as first-line treatment for soft tissue infections caused by It is used frequently in the elderly and is an established cause of cholestatic liver injury. Risk factors for cholestasis include prolonged duration of treatment, female sex and older age. Elderly patients are also more likely to suffer from comorbidities and polypharmacy, which increases the incidence of drug-induced liver injury and hospitalisation, which in turn can lead to irreversible deterioration in functional baseline. Our case report aims to raise awareness of flucloxacillin-induced liver injury in elderly patients and to encourage the use of alternative treatments and/or limited duration. We advocate for further research into individualised treatments and new diagnostic techniques in patients with painless jaundice based on their genotype.
Topics: Aged; Chemical and Drug Induced Liver Injury; Chemical and Drug Induced Liver Injury, Chronic; Cholestasis; Female; Floxacillin; Humans; Liver
PubMed: 33958360
DOI: 10.1136/bcr-2020-241071 -
British Journal of Clinical Pharmacology Dec 2021Oral flucloxacillin may be coadministered with probenecid to reduce flucloxacillin clearance and increase attainment of pharmacokinetic-pharmacodynamic (PK/PD) targets.... (Observational Study)
Observational Study
UNLABELLED
Oral flucloxacillin may be coadministered with probenecid to reduce flucloxacillin clearance and increase attainment of pharmacokinetic-pharmacodynamic (PK/PD) targets. The aims of this study were to develop a population PK model of free flucloxacillin when administered orally with probenecid, and to identify optimal dosing regimens for this combination.
METHODS
We performed a prospective observational study of adults (45 participants) treated with oral flucloxacillin 1000 mg and probenecid 500 mg 8-hourly for proven or probable staphylococcal infections. Steady-state mid-dose-interval flucloxacillin measurements (45 concentrations) were combined with existing data from a crossover study of healthy participants receiving flucloxacillin with and without probenecid (11 participants, 363 concentrations). We developed a population pharmacokinetic model of free flucloxacillin concentrations within Monolix, and used Monte Carlo simulation to explore optimal dosing regimens to attain PK/PD targets proposed in the literature (free drug time above minimum inhibitory concentration).
RESULTS
Flucloxacillin disposition was best described by a 1-compartment model with a lag time and first-order absorption. Free flucloxacillin clearance depended on probenecid, allometrically-scaled fat free mass (FFM) and estimated glomerular filtration rate (eGFR). Predicted PK/PD target attainment was suboptimal with standard dosing regimens with flucloxacillin alone, but substantially improved in the presence of probenecid.
CONCLUSION
The simulation results reported can be used to identify dose regimens that optimise flucloxacillin exposure according to eGFR and FFM. Patients with higher FFM and eGFR may require the addition of probenecid and 6-hourly dosing to achieve PK/PD targets. The regimen was well-tolerated, suggesting a potential for further evaluation in controlled clinical trials to establish efficacy.
Topics: Adult; Anti-Bacterial Agents; Cross-Over Studies; Floxacillin; Humans; Microbial Sensitivity Tests; Monte Carlo Method; Probenecid
PubMed: 33963595
DOI: 10.1111/bcp.14887