Acquired pyroglutamic acidosis due to long-term dicloxacillin and paracetamol use.

An 85-year-old man with a background of transfusion-dependent chronic myelomonocytic leukaemia and chronic kidney disease stage III presented with symptomatic anaemia, acute kidney injury, sepsis and high anion gap metabolic acidosis (HAGMA). Initial treatment with intravenous antibiotics and blood transfusion was complicated by transfusion-associated circulatory overload, necessitating diuresis and non-invasive ventilation. Despite gradual clinical improvement, the patient's HAGMA persisted, and no cause was identified on urine testing or renal ultrasound. As the patient was on long-term dicloxacillin for infective endocarditis prophylaxis and regular paracetamol, pyroglutamic acidosis (PGA) (5-oxoproline acidosis) was considered. This was later confirmed with elevated serum levels, and the HAGMA resolved following cessation of these medications. Although considered an uncommon cause of HAGMA, PGA is likely also under-recognised, and to our knowledge, this may be the second reported case in the context of dicloxacillin.

Use of Dicloxacillin and Risk of Pregnancy among Users of Oral Contraceptives.

The antibiotic dicloxacillin has been shown to induce drug-metabolizing CYP enzymes to a clinically relevant extent. In this study, we investigated whether the use of dicloxacillin confers an increased risk of unwanted pregnancy among oral contraceptive users. The study population comprised Danish women falling pregnant (1997-2015) during oral contraceptive use, defined as having filled a prescription for an oral contraceptive within 120 days both before and after the estimated date of conception. Data were analysed using a case-crossover approach. For each woman, we assessed the use of dicloxacillin preceding the date of conception and during 10 previous control periods and estimated the odds ratio for such unintended pregnancies associated with the use of dicloxacillin. Among 364 women using dicloxacillin prior to conception, 40 (11%) were exposed to dicloxacillin at the time of conception, yielding an odds ratio (OR) associating use of dicloxacillin to unintended pregnancy of 1.18 (95% CI 0.84-1.65). Supplementary and sensitivity analyses generally returned similar estimates, except for a slightly increased risk among users of progestogen-only oral contraceptives (OR 1.83, 95% CI 0.63-5.34). Analysis of other antibiotics as negative controls yielded results close to unity (ORs ranging from 0.83 to 1.13). In conclusion, our study found no evidence for an increased risk of oral contraceptive failure when using dicloxacillin. However, acknowledging study limitations, we suggest the use of supplementary barrier methods during treatment with dicloxacillin, until our findings are confirmed in further studies.

Systemic thioridazine in combination with dicloxacillin against early aortic graft infections caused by Staphylococcus aureus in a porcine model: In vivo results do not reproduce the in vitro synergistic activity.

INTRODUCTION: Conservative treatment solutions against aortic prosthetic vascular graft infection (APVGI) for inoperable patients are limited. The combination of antibiotics with antibacterial helper compounds, such as the neuroleptic drug thioridazine (TDZ), should be explored. AIM: To investigate the efficacy of conservative systemic treatment with dicloxacillin (DCX) in combination with TDZ (DCX+TDZ), compared to DCX alone, against early APVGI caused by methicillin-sensitive Staphylococcus aureus (MSSA) in a porcine model. METHODS: The synergism of DCX+TDZ against MSSA was initially assessed in vitro by viability assay. Thereafter, thirty-two pigs had polyester grafts implanted in the infrarenal aorta, followed by inoculation with 106 CFU of MSSA, and were randomly administered oral systemic treatment with either 1) DCX or 2) DCX+TDZ. Treatment was initiated one week postoperatively and continued for a further 21 days. Weight, temperature, and blood samples were collected at predefined intervals. By termination, bacterial quantities from the graft surface, graft material, and perigraft tissue were obtained. RESULTS: Despite in vitro synergism, the porcine experiment revealed no statistical differences for bacteriological endpoints between the two treatment groups, and none of the treatments eradicated the APVGI. Accordingly, the mixed model analyses of weight, temperature, and blood samples revealed no statistical differences. CONCLUSION: Conservative systemic treatment with DCX+TDZ did not reproduce in vitro results against APVGI caused by MSSA in this porcine model. However, unexpected severe adverse effects related to the planned dose of TDZ required a considerable reduction to the administered dose of TDZ, which may have compromised the results.

A retrospective study of acute kidney injury in hip arthroplasty patients receiving gentamicin and dicloxacillin.

Background and purpose - Acute kidney injury is a known complication of antibiotic use. Antibiotic prophylaxis is essential to prevent periprosthetic infections after total hip replacement. We experienced a rise in the incidence of acute kidney injury (AKI), and in an effort to solve this problem, we changed our antibiotic prophylaxis protocol. We investigated whether removing gentamicin from our antibiotic protocol would cause fewer and less severe cases of renal impairment. Patients and methods - We performed a retrospective study involving 136 cases of total hip replacement, with 66 patients receiving dicloxacillin and gentamicin and 70 patients receiving dicloxacillin alone. Results - We found less cases of AKI in the dicloxacillin group (p = 0.03): the mean creatine level in the dicloxacillin/gentamicin group was 126 (25-422) µmol/L whereas it was 93 (39-278) µmol/L in the group that received dicloxacillin alone. We also found that cases were less severe in the dicloxacillin group than in the dicloxacillin/gentamicin group (p = 0.02). The relative risk of developing AKI was 3 times higher if dicloxacillin and gentamicin were both used (p = 0.02). Interpretation - After removing gentamicin, there were fewer and less severe cases of acute kidney injury.

Safety and pharmacokinetics of dicloxacillin in healthy Chinese volunteers following single and multiple oral doses.

BACKGROUND: Dicloxacillin, a semisynthetic isoxazolyl penicillin antibiotic, has antimicrobial activity against a wide variety of gram-positive bacteria including Staphylococcus aureus, Streptococcus pyogenes, Streptococcus pneumonia, Streptococcus epidermidis, Streptococcus viridans, Streptococcus agalactiae, and Neisseria meningitidis. The objective of this study was to evaluate the safety and pharmacokinetic profile of dicloxacillin after single and multiple oral dose in healthy Chinese volunteers. METHODS: A single-center, open-label, randomized, two-phase study was conducted in 16 subjects. In the single-dose phase, subjects were randomly assigned to receive single doses of 0.25, 0.5, 1.0, and 2.0 g of dicloxacillin sodium capsule in a 4-way crossover design with a 5-day washout period between administrations. In the multiple-dose phase, subjects were assigned to receive 0.25 or 0.5 g every 6 hours for 3 days in a 2-way crossover design. Plasma and urine pharmacokinetic samples were assayed by a validated high-performance liquid chromatography-tandem mass spectrometry method. Pharmacokinetic parameters were calculated and analyzed statistically. Safety assessments were conducted throughout the study. RESULTS: Following a single oral dose of 0.25-2.0 g dicloxacillin sodium, the maximum plasma drug concentration (Cmax) and the corresponding values for the area under the concentration- time curve from 0 to 10 hours (AUC0-10 h) increased in a dose-proportional manner. The mean elimination half-life (t1/2) was in the range of 1.38-1.71 hours. Dicloxacillin was excreted in its unchanged form via the kidney, with no tendency of accumulation, and varied from 38.65% to 50.10%. No appreciable accumulation of drug occurred with multiple oral doses of dicloxacillin. No serious adverse events were reported. Adverse events were generally mild. CONCLUSION: Dicloxacillin was safe and well tolerated in the volunteers and displayed linear increases in the Cmax and AUC0-10 h values.

Dicloxacillin: a higher risk than cloxacillin for infusion phlebitis.

Ever since dicloxacillin and cloxacillin were introduced in the 1960s, it has been known that they are associated with a high incidence of infusion phlebitis. Some in vitro studies and clinical experience have indicated that dicloxacillin is the more vessel-irritating of the 2 drugs. In this prospective observational study on 39 patients with 111 peripheral venous catheters (PVCs), the incidence of infusion phlebitis was compared between these 2 drugs. The incidence of phlebitis was 38% with dicloxacillin and 21% with cloxacillin; which, compared by logistic regression with other risk factors as covariates, was significant [odds ratio 5.06, 95% confidence interval (95% CI) 1.45-17.60]. Since the duration of catheterization is also an important risk factor, Cox regression was performed, and the difference between the 2 drugs was still significant (proportional hazard rate 3.48, 95%, CI 1.64-7.38). The only other significant risk factor found in the study was the insertion site; the risk was higher in PVCs inserted in the forearm/antecubital fossa than in the hand/wrist. The infusion time and dilution of the infusate were not significant risk factors.

Randomized comparison of linezolid (PNU-100766) versus oxacillin-dicloxacillin for treatment of complicated skin and soft tissue infections.

This randomized, double-blind, multicenter trial compared the efficacy and safety of linezolid, an oxazolidinone, with those of oxacillin-dicloxacillin in patients with complicated skin and soft tissue infections. A total of 826 hospitalized adult patients were randomized to receive linezolid (600 mg intravenously [i.v.]) every 12 h or oxacillin (2 g i.v.) every 6 h; following sufficient clinical improvement, patients were switched to the respective oral agents (linezolid [600 mg orally] every 12 h or dicloxacillin [500 mg orally] every 6 hours). Primary efficacy variables were clinical cure rates in both the intent-to-treat (ITT) population and clinically evaluable (CE) patients and microbiological success rate in microbiologically evaluable (ME) patients. Safety and tolerability were evaluated in the ITT population. Demographics and baseline characteristics were similar across treatment groups in the 819 ITT patients. In the ITT population, the clinical cure rates were 69.8 and 64.9% in the linezolid and oxacillin-dicloxacillin groups, respectively (P = 0.141; 95% confidence interval -1.58 to 11. 25). In 298 CE linezolid-treated patients, the clinical cure rate was 88.6%, compared with a cure rate of 85.8% in 302 CE patients who received oxacillin-dicloxacillin. In 143 ME linezolid-treated patients, the microbiological success rate was 88.1%, compared with a success rate of 86.1% in 151 ME patients who received oxacillin-dicloxacillin. Both agents were well tolerated; most adverse events were of mild-to-moderate intensity. No serious drug-related adverse events were reported in the linezolid group. These data support the use of linezolid for the treatment of adults with complicated skin and soft tissue infections.

Nephrotoxicity by dicloxacillin and gentamicin in 163 patients with intertrochanteric hip fractures.

Of 163 patients with intertrochanteric hip fractures 87 received 2 g dicloxacillin and 240 mg of gentamicin preoperatively, and 76 patients had no antibiotic prophylaxis. Preoperative antibiotic prophylaxis was not shown to have any significant effect on wound infections. However, 16 reversible and 1 irreversible cases of kidney toxicity were found among patients receiving antibiotic prophylaxis, whereas there were only four cases of reversible kidney damage among the patients not receiving antibiotics.

Postmarketing surveillance: strengths and limitations. The flucloxacillin-dicloxacillin story.

Spontaneous reporting of adverse drug reactions continues to be the principal method used for monitoring the safety of marketed drugs. Despite the many successes attributed to these schemes, they can reliably detect only a small fraction of the range of possible drug-related events and provide virtually no useful quantitative data. Some of the limitations of spontaneous reporting were demonstrated recently in relation to flucloxacillin. Reports in Australia suggested the likelihood of an unacceptable risk of flucloxacillin-associated jaundice, but the data from spontaneous reporting in countries with apparently similar use of the drug, such as New Zealand and the UK, were insufficient to confirm or refute this proposition. Spontaneous monitoring should be supplemented by the systematic monitoring of cohorts of users of new drugs, using record-linkage to track their subsequent health. Although several impediments exist to the introduction of such a scheme in Australia, consideration should be given to addressing how such a system might be implemented.

Prosthetic heart valve thrombosis during dicloxacillin therapy.

A 76-year-old woman receiving warfarin after aortic valve replacement experienced prosthetic valve thrombosis during dicloxacillin therapy. Successful thrombolysis was achieved with tissue plasminogen activator. The international normalized ratio (INR) on admission was reduced to 1.4 and an increased warfarin dosage was required for three weeks following discontinuation of dicloxacillin treatment in order to maintain therapeutic INRs. Careful monitoring of INRs and titration of the warfarin dosage is recommended when dicloxacillin is prescribed to patients receiving warfarin.

Long-term treatment of a breastfeeding mother with fluconazole-resolved nipple pain caused by yeast: a case study.

This case follows a breastfeeding mother with cracked nipples undergoing antibiotic treatment (dicloxacillin) for mastitis. Nipple candidiasis also presented with burning, stinging pain radiating from the nipples into the breast, lasting throughout feedings and beyond. Over a 7-week period, the asymptomatic infant was treated with the oral antifungal, nystatin. After other antifungal treatment regimens (oral nystatin, tristatin ointment) had been deemed unsuccessful for the mother, the physician prescribed fluconazole (200 mg loading dose plus 100 mg/day for 15 days) which reduced, but did not eliminate, the nipple yeast and accompanying pain. Fluconazole was continued for an additional 30 days (200 mg/day) for a total of 6 weeks of treatment with this medication. Concurrently, a topical yeast medication (tristatin ointment) was used for a total of 8 weeks on the nipples/areola, after which the overt pain was resolved. Although the mastitis resolved after 1 week, the cracked nipples did not completely heal for several months. During the initial 3 weeks of treatment, neither over-the-counter pain medication nor acetaminophen with codeine relieved this mother's pain. Hydrocodone bitartrate and acetaminophen (10/650 mg/tablet) (Lorcet) offered the pain relief necessary for this mother to continue to breastfeed.

Potential interaction between warfarin and dicloxacillin.

OBJECTIVE: To report a case and retrospective review of seven patients who experienced a decrease in prothrombin time during concomitant administration of warfarin and dicloxacillin. CASE SUMMARY: A 41-year-old man receiving warfarin 22 mg/wk with a final baseline prothrombin time (PT) of 20.7 sec was prescribed dicloxacillin 500 mg qid for 10 days. Plasma collected for PT determinations was also used to measure trough warfarin R- and S- enantiomer concentrations. The PT and S- and R-warfarin concentrations decreased 17%, 25%, and 20%, respectively, on day 5 after initiation of dicloxacillin. For the retrospective review, the mean PT decreased 17.0% (range 10.5-25.9%) as soon as 4 days after the initiation of dicloxacillin. DISCUSSION: Our observations, which are consistent with those of two previously published reports, suggest a close temporal relationship between the administration of dicloxacillin and a decreased anticoagulant effect of warfarin. Limited data from our patient further suggest that this may result from declines in systemic warfarin concentrations. The time course of the fall of PTs appears to occur within 4-5 days; return of the PT to baseline after dicloxacillin administration is stopped appears to take up to 3 weeks. Until further controlled studies are conducted to confirm this interaction, clinicians should be aware that patients may be at risk for a decreased anticoagulant effect of warfarin when dicloxacillin is given concomitantly. CONCLUSIONS: Careful monitoring of international normalized ratios and titration of the warfarin dosage is recommended on initiation and for 3 weeks after discontinuation of dicloxacillin in patients receiving warfarin.

A comparative study of the efficacy, safety and tolerance of azithromycin, dicloxacillin and flucloxacillin in the treatment of children with acute skin and skin-structure infections.

An open, randomized, multicentre study was undertaken to compare a three-day regimen of azithromycin with a seven-day course of dicloxacillin or flucloxacillin in the treatment of 118 children (aged 2-12 years) with clinically diagnosed acute skin and skin-structure infections. Sixty patients received a single daily dose of azithromycin of 10 mg/kg for three days, whilst 58 received a cloxacillin ester: either dicloxacillin (n = 49) at a daily dose of 12.5-25 mg/kg (depending on severity of infection); or flucloxacillin (n = 9) at 250-2000 mg/day (depending on age). Both cloxacillin esters were administered in four divided doses for seven days. Clinical, safety and, where possible, bacteriological assessments were made before therapy and after 3 to 5 and 7 to 10 days of treatment. A successful clinical response (cure and improvement) was recorded in 57 of 59 (97%) of evaluable azithromycin patients, and in 57 of 58 (98%) of cloxacillin ester patients. Eradication of the key pathogens was 31 of 34 (91%) and 34 of 35 (97%) for Staphylococcus aureus, and 5 of 5 and 4 of 4 for Streptococcus pyogenes in the azithromycin and cloxacillin ester groups, respectively. Both medications were well tolerated, with mild to moderate side-effects (abdominal pain and vomiting) occurring in two patients in each group, and laboratory abnormalities (elevated eosinophil count) in one patient in each group. There were no withdrawals from therapy. The results of this study suggest that azithromycin is as effective and as well tolerated as a cloxacillin ester antibiotic in the treatment of children with acute skin and skin-structure infections.