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Background: First-line treatments for methicillin-susceptible S. aureus (MSSA) bacteraemia are nafcillin, oxacillin, or cefazolin. Regional shortages of these antibiotics force clinicians to use other options like dicloxacillin and cephalotin. This study aims to describe and compare the safety and efficacy of cephalotin and dicloxacillin for the treatment of MSSA bacteraemia. Methods: This retrospective study was conducted in a referral centre in Mexico City. We identified MSSA isolates in blood cultures from 1 January 2012 to 31 December 2022. Patients ≥ 18 years of age, with a first episode of MSSA bacteraemia, who received cephalotin or dicloxacillin as the definitive antibiotic treatment, were included. The primary outcome was in-hospital all-cause mortality. Results: We included 202 patients, of which 48% (97/202) received cephalotin as the definitive therapy and 52% (105/202) received dicloxacillin. In-hospital all-cause mortality was 20.7% (42/202). There were no differences in all-cause in-hospital mortality between patients receiving cephalotin or dicloxacillin (20% vs. 21%, p = 0.43), nor in 30-day all-cause mortality (14% vs. 18%, p = 0.57) or 90-day all-cause mortality (24% vs. 22%, p = 0.82). No severe adverse reactions were associated with either antibiotic. Conclusions: Cephalotin and dicloxacillin were equally effective for treating MSSA bacteraemia, and both showed an adequate safety profile. [ABSTRACT FROM AUTHOR]

In this research, natural compounds from Calotropisprocera were screened according to their antimicrobial activity against the pathogenic microbes selected as E. coli, S. aureus, Traypanosomabrucei, Moraxella catarrhalis, and Leishmaniaamazonensis. A 3D‐QSAR study was performed that evaluated the correlation of the structural parameters for the antimicrobial activity of the natural compounds which were selected based on their antimicrobial in‐vivo and in‐vitro studies previously. The screened active compounds were further studied by molecular docking to analyze the various interactions between the ligands and target proteins. Molecular docking was also performed with the three FDA‐approved antibiotics Cephalexin, Dicloxacillin, and Levofloxacin, having antimicrobial potential, and their results were compared with the docking results of the hit compounds. Results of ADME/T study of the compounds revealed that the two compounds stigmasterol and caryophyllene oxide are the hit compounds having no toxicity, best values of TPSA and average molecular weight. Validation of the docking results was also carried out by re‐docking as well as by molecular dynamic simulation. DFT study was also carried out to explore the stability and chemical properties of active compounds. Results showed that caryophyllene oxide is the hit compound because of the highest Moldock score with 3VOB protein, better than standard drugs and according to dynamic simulation analysis. Therefore, the derived results in these studies provide crucial information for designing antimicrobial drugs by using natural compounds that have better antimicrobial activity. [ABSTRACT FROM AUTHOR]

Background In the POET (Partial Oral Endocarditis Treatment) trial, oral step-down therapy was noninferior to full-length intravenous antibiotic administration. The aim of the present study was to perform pharmacokinetic/pharmacodynamic analyses for oral treatments of infective endocarditis to assess the probabilities of target attainment (PTAs). Methods Plasma concentrations of oral antibiotics were measured at day 1 and 5. Minimal inhibitory concentrations (MICs) were determined for the bacteria causing infective endocarditis (streptococci, staphylococci, or enterococci). Pharmacokinetic/pharmacodynamic targets were predefined according to literature using time above MIC or the ratio of area under the curve to MIC. Population pharmacokinetic modeling and pharmacokinetic/pharmacodynamic analyses were done for amoxicillin, dicloxacillin, linezolid, moxifloxacin, and rifampicin, and PTAs were calculated. Results A total of 236 patients participated in this POET substudy. For amoxicillin and linezolid, the PTAs were 88%–100%. For moxifloxacin and rifampicin, the PTAs were 71%–100%. Using a clinical breakpoint for staphylococci, the PTAs for dicloxacillin were 9%–17%. Seventy-four patients at day 1 and 65 patients at day 5 had available pharmacokinetic and MIC data for 2 oral antibiotics. Of those, 13 patients at day 1 and 14 patients at day 5 did only reach the target for 1 antibiotic. One patient did not reach target for any of the 2 antibiotics. Conclusions For the individual orally administered antibiotic, the majority reached the target level. Patients with sub-target levels were compensated by the administration of 2 different antibiotics. The findings support the efficacy of oral step-down antibiotic treatment in patients with infective endocarditis. [ABSTRACT FROM AUTHOR]

Background: First-line treatments for methicillin-susceptible S. aureus (MSSA) bacteraemia are nafcillin, oxacillin, or cefazolin. Regional shortages of these antibiotics force clinicians to use other options like dicloxacillin and cephalotin. This study aims to describe and compare the safety and efficacy of cephalotin and dicloxacillin for the treatment of MSSA bacteraemia. Methods: This retrospective study was conducted in a referral centre in Mexico City. We identified MSSA isolates in blood cultures from 1 January 2012 to 31 December 2022. Patients ≥ 18 years of age, with a first episode of MSSA bacteraemia, who received cephalotin or dicloxacillin as the definitive antibiotic treatment, were included. The primary outcome was in-hospital all-cause mortality. Results: We included 202 patients, of which 48% (97/202) received cephalotin as the definitive therapy and 52% (105/202) received dicloxacillin. In-hospital all-cause mortality was 20.7% (42/202). There were no differences in all-cause in-hospital mortality between patients receiving cephalotin or dicloxacillin (20% vs. 21%, p = 0.43), nor in 30-day all-cause mortality (14% vs. 18%, p = 0.57) or 90-day all-cause mortality (24% vs. 22%, p = 0.82). No severe adverse reactions were associated with either antibiotic. Conclusions: Cephalotin and dicloxacillin were equally effective for treating MSSA bacteraemia, and both showed an adequate safety profile.

The Huatanay River in Cusco-Peru, is affected by wastewater discharges along its course. In order to evaluate this impact, we evaluate antibiotic residues and their impact on the increase of bacterial resistance in the city of Cusco treatment plant. For this purpose, water samples from the influent and effluent of the treatment plant were analyzed by chromatographic methods; additionally, sensitivity tests were performed with three bacterial strains (Escherichia coli, Salmonella sp., and Klebsiella sp.), which were isolated from the same place. Six antibiotic residues were identified (ceftriaxone, amoxicillin, trimethoprim, sulfamethoxazole, dicloxacillin, and lincomycin). Those found in the highest concentration were: amoxicillin (91495 and 0 μg/L) and lincomycin (33970 and 10800 μg/L) in the influent and effluent, respectively. There is more resistance in the effluent than the influent in the case of E. coli shows resistance in the effluent to cephalexin (30 μg) and azithromycin (15 μg). Salmonella sp. is resistant to amoxicillin (15 μg), dicloxacillin (1 μg), lincomycin (2 μg), ceftriaxone (30 μg), cephalexin (30 μg), and ciprofloxacin (5 μg). Finally, Klebsiella sp. is sensitive to ceftriaxone (30 μg), amoxicillin (15 μg), and cephalexin (30 μg). This confirms that the antibiotic residues contained in the wastewater of Cusco generate resistance in the isolated bacteria. [ABSTRACT FROM AUTHOR]

AimThe aim of this study was to study potential cytochrome P450 (CYP) induction by dicloxacillin.MethodsWe performed an open-label, randomized, two-phase, five-drug clinical pharmacokinetic cocktail crossover study in 12 healthy men with and without pretreatment with 1 g dicloxacillin three times daily for 10 days. Plasma and urine were collected over 24 h and the concentration of all five drugs and their primary metabolites was determined using a liquid chromatography coupled to triple quadrupole mass spectrometry method. Cryopreserved primary human hepatocytes were exposed to dicloxacillin for 48 h and changes in gene expression and the activity of CYP3A4, CYP2C9, CYP2B6 and CYP1A2 were investigated. The activation of nuclear receptors by dicloxacillin was assessed using luciferase assays.ResultsA total of 10 days of treatment with dicloxacillin resulted in a clinically and statistically significant reduction in the area under the plasma concentration-time curve from 0 to 24 h for omeprazole (CYP2C19) {geometric mean ratio [GMR] [95% confidence interval (CI)]: 0.33 [0.24, 0.45]}, tolbutamide (CYP2C9) [GMR (95% CI): 0.73 (0.65, 0.81)] and midazolam (CYP3A4) [GMR (95% CI): 0.54 (0.41, 0.72)]. Additionally, other relevant pharmacokinetic parameters were affected, indicating the induction of CYP2C- and CYP3A4-mediated metabolism by dicloxacillin. Investigations in primary hepatocytes showed a statistically significant dose-dependent increase in CYP expression and activity by dicloxacillin, caused by activation of the pregnane X receptor.ConclusionsDicloxacillin is an inducer of CYP2C- and CYP3A-mediated drug metabolism, and we recommend caution when prescribing dicloxacillin to users of drugs with a narrow therapeutic window.

We present a case with a phototoxic reaction following topical use of NSAID. The phototoxic reaction was initially mistaken for cellulitis which led to treatment with dicloxacillin, which led to an exanthematous drug eruption. The patient was treated with topical clobetasol propionate and oral non‐sedating antihistamines. Follow‐up revealed post‐inflammatory hypopigmentation. [ABSTRACT FROM AUTHOR]

Abstract We present a case with a phototoxic reaction following topical use of NSAID. The phototoxic reaction was initially mistaken for cellulitis which led to treatment with dicloxacillin, which led to an exanthematous drug eruption. The patient was treated with topical clobetasol propionate and oral non‐sedating antihistamines. Follow‐up revealed post‐inflammatory hypopigmentation.

In the present work, a natural zeolite was first treated with a sodium chloride salt and subsequently modified with different cetyltrimethylammonium bromide (CTAB) concentrations for dicloxacillin removal. All the employed materials are characterized by several analytical techniques. Antibiotic sorption behavior was evaluated according to diverse parameters such as the effect of contact time, initial concentration, and pH by a batch system. Experimental results showed that the cationic surfactant treatment benefited dicloxacillin sorption. Kinetic results indicated that the equilibrium time was reached at 54 h and a maximum adsorption capacity of 1.072 and 1.051 mg/g for both modified zeolites at 25 mmol/L and 50 mmol/L, respectively. According to the kinetic data, the pseudo-second-order model adjust the best. Obtained adsorption equilibrium results, adsorption isotherms adjust well to the linear model for both adsorbents with both materials, indicating a partition mechanism. Dicloxacillin species present at different pH values and the net surface charge of the modified adsorbents influence the adsorption process. [ABSTRACT FROM AUTHOR]

ObjectiveAntibiotic use rates have declined dramatically since the 1990s. We aimed to determine if, when, and at what level the decline in antibiotic-dispensing rates ended and which diagnoses contributed to the trends.MethodsAntibiotic dispensings and diagnoses were obtained from 2 health insurers for 3- to

This study focused on the use of Indian almond leaf biomass, a local plant widely found in Thailand, on removal of dicloxacillin from pharmaceutical waste water by biosorption. The biosorption characteristics of dicloxacillin were investigated in terms of equilibrium, kinetics and thermodynamics. Optimum biosorption conditions were determined from pH, initial dicloxacillin concentration, biomass dosage, contact time, and temperature. The maximum adsorption capacity was 86.93 % (pH 6.0, 0.1 g/L biomass, dicloxacillin concentration 20 mg/L, contact time 24 h, temperature 283.15 K). The thermodynamic parameters (298.15 K), free energy change, enthalpy change and entropy change were -3475.79 J/mol, −25.36 kJ/mol, and −73.40 J/mol/K, respectively. The best interpretation for the experimental data was given by the Langmuir isotherm with correlation coefficient of 0.965. The results were found to tie in well with pseudo-second-order kinetics. Considering the cost-effectiveness, Indian almond leaf biomass is considered to be suitable to remove dicloxacillin from pharmaceutical waste water.

Environmental problems such as bacterial resistance have been generated by indiscriminate use of antibiotics, because free-living bacteria have a great ability to adapt to unfavorable environmental, since they develop several defense mechanisms such as genetic resistance, in response of being in contact with this contaminant present in its environment, which is why they acquire special importance due to its biodegradation capacity. In this study, the biodegradation of 40 μg/mL of dicloxacillin with free-living bacteria was evaluated. Wastewater samples were collected from a hospital, from which five resistant strains were isolated, characterized, and identified: Pseudomonas aeruginosa, Citrobacter freundii, Klebsiella pneumoniae, and two different strains of Escherichia coli, being the last one, the most resistant according to the determination of the minimum inhibitory concentration, so degradation was carried out with this strain and in bacterial consortium. Biodegradation was quantified by high-resolution liquid chromatography (HPLC) and the results showed that both the consortium and Pseudomonas aeruginosa are highly efficient because the degradation of the antibiotic was 100%, in a time of 3.5 h and 52 h, respectively, and even metabolize the degradation products. [ABSTRACT FROM AUTHOR]

A simple, selective method was developed for simultaneous estimation of Cefixime, Ornidazole and Dicloxacillin in blood plasma and validated as per the US FDA guidelines. Extraction process was accomplished by protein precipitation method. By employing cefixime as internal standard in methyl alcohol solvent, the proteins got precipitated. Single method can be used for separating combination drugs, where any one drug can act as an internal standard. The drugs were analyzed by triple quadrupole mass spectrometer using photomultiplier tube as detector, with the electron spray ionization technique of positive and negative mode on a shim-pack solar C18(50 x 4.6mm i.d, 5µm) column. The mobile phase comprising of 10mM ammonium acetate and Methyl alcohol with the ratio 10:90v/v, pH 6.0. After the evaluation of different sample pretreatment techniques, protein precipitation was found to be satisfactory, offering good recovery values. The linearity of Ornidazole and Dicloxacillin found within range of 4.0 - 80.0µg/ml and 1.5 - 30.0µg/ml respectively which is consistently accurate for plotting curve. The correlation coefficient of Ornidazole and Dicloxacillin were 0.9936 and 0.9994 respectively. The Limit of detection of Ornidazole and Dicloxacillin was found to be 330ng/ml and 123.5ng/ml respectively and their Limit of quantification values were 1000ng/ml and 375ng/ml respectively. Different constituents of plasma will not affect the effective recovery of the drugs. The established method can be used for the quantification of drugs in plasma for BA-BE studies and biopharmaceutical sciences. [ABSTRACT FROM AUTHOR]

BackgroundWidespread use of broad-spectrum antibiotics contributes to increasing rates of bacterial resistance to antibiotics. Second-generation macrolides have become popular for use among children because of their broad spectrum and favorable dosing and side-effect profiles, although experts do not generally recommend them for use as initial treatment of infections among younger children.ObjectiveTo assess trends in second-generation macrolide use from 1996 to 2000 among children treated as outpatients in 9 US health plans, including associated diagnoses and use as initial treatment.MethodsWe sampled claims data for 25000 children, 3 months to

Wei Yu,1,2,* Jinru Ji,1,* Tingting Xiao,1 Chaoqun Ying,1 Jiaheng Fang,3 Ping Shen,1 Yonghong Xiao1 1State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, 2Department of Infectious Diseases, Zhejiang Provincial People’s Hospital, 3Department of Gastroenterology, Hang Zhou Normal University Affiliated Hospital, Hangzhou, People’s Republic of China *These authors contributed equally to this work Background: Dicloxacillin, a semisynthetic isoxazolyl penicillin, exhibits antimicrobial activity against a wide variety of Gram-positive bacteria, as well as stability against penicillinases and low level of toxicity. The objective of this study was to obtain optimal dosing regimen of oral administration of dicloxacillin by analyzing the pharmacokinetic (PK) index in healthy volunteers and in vitro antibacterial activity by using Monte Carlo simulation. Materials and methods: A total of 867 clinical isolates from community-onset infections were collected from 31 secondary hospitals in People’s Republic of China. The minimum inhibitory concentration (MIC) values of dicloxacillin were determined by the agar dilution method. Based on the MICs and the PK parameters of different dosage regimens, Monte Carlo simulation was performed to simulate the PK/pharmacodynamic indices of 250 mg once-daily (qd), 500 mg qd, 1,000 mg qd, 2,000 mg qd, 250 mg every 6 hours (q6h), and 500 mg q6h, respectively. The probability of target attainment was estimated at each MIC value, and the cumulative fraction of response (CFR) was calculated to evaluate the efficacy of these regimens. Results: Dicloxacillin showed poor antibacterial activity against Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae. Resistance to dicloxacillin was observed in 7.5% of coagulase-negative Staphylococcus (CNS) isolates and 9.2% of other Streptococcus isolates, whereas 1.5% of methicillin-sensitive Staphylococcus aureus (MSSA) was resistant to dicloxacillin. Multiple-dose regimens could obtain higher CFR than single-dose regimens against H. influenza and S. pneumoniae. However, all dosing regimens against MSSA achieved CFR ≥90%. Meanwhile, dosing regimen of 2,000 mg qd, 250 mg q6h, and 500 mg q6h could achieve >90% of CFR for CNS. For other Streptococcus isolates, multiple-dose regimens achieved CFR ≥90%. Conclusion: Dicloxacillin has a significant antibacterial activity against MSSA, CNS, and other Streptococcus isolates. The simulation results suggest that dicloxacillin 250 mg q6h and 500 mg q6h dosing regimens may be recommended for clinical applications, especially for community-onset infections. Keywords: pharmacokinetics, pharmacodynamics, PK/PD index, dosage regimens, MSSA, CNS

Patients with a durable, continuous flow left ventricular assist device (CF-LVAD) require anticoagulation with warfarin to prevent thromboembolic events. Driveline infections (DLIs) are a common CF-LVAD complication. A common pathogen implicated in DLI is oxacillin-sensitive Staphylococcus aureus (OSSA), which is effectively treated by oral dicloxacillin. Previous published experiences have observed a significant drug interaction between dicloxacillin and warfarin resulting in decreased international normalized ratio (INR) and increased warfarin dosing requirements. We sought to analyze the effect of dicloxacillin on INR and warfarin dose when used for DLI in our CF-LVAD program. Five of 106 patients having received an CF-LVAD at our institution met the inclusion criteria for this case series. These patients required a mean 51.8% (standard deviation of 29.8%) weekly warfarin dose increase to restore INR to the therapeutic range after the addition of dicloxacillin. Three of the five patients subsequently had their dicloxacillin discontinued, with a mean decrease in weekly warfarin dose of 30.6% (standard deviation of 19.1%). In our experience, when coalesced with prior published reports, an empiric warfarin dose increase of 25% to 33% is reasonable upon initiation of dicloxacillin and an empiric warfarin dose reduction of 10% to 15% is recommended upon discontinuation of dicloxacillin. Close INR follow-up is warranted during and after dicloxacillin treatment. [ABSTRACT FROM AUTHOR]

Backgound: Cellulitis is commonly used to indicate a nonnecrotizing inflammation of the skin and subcutaneous tissues, a process usually related to acute infection that does not involve the fascia or muscles. Cellulitis is characterized by localized pain, swelling, tenderness, erythema, and warmth, cellulitis has been classically considered to be an infection without formation of abscess (nonpurulent), purulent drainage, or ulceration. Objective: The aim of the current work was to evaluate the efficacy of standard treatment for cases of cellulitis and identify other treatment options if needed in local community. Patients and methods: This prospective study was conducted at Department of General Surgery, Al-Azhar university hospitals (Al-Hussin & Said Galal hospitals). This study carried out on 100 consecutive patients with non-purulent cellulitis from 23/2/2017 to 1/5/2018 to allow a minimum follow-up period of at least 4 months for the last case follow upon. Clinical response to dicloxacillin, amoxicillin, and cephalexin was evaluated. Results: Age, sex, presentation, sit of non purulent cellulitis and result were recorded. Cellulitis was found to be more common in geriatric patients and slightly more in females. Most patients had lower limb cellulitis, and only little patients had an additional sit as orbit, hand and genitalia. 83 cases have good clinical response and 17 cases have poor clinical response within 7 days to dicloxacillin, amoxicillin, and cephalexin. Conclusion: Dicloxacillin, amoxicillin, or cephalexin are effective in most cases of cellulitis with gram positive organisms as Streptococcal and staphylococcal species. [ABSTRACT FROM AUTHOR]

The review presents data on the mechanisms of the emergence and development of antibiotic resistance of microorganisms. Modern approaches and ways to overcome them are considered. [ABSTRACT FROM AUTHOR]

Abstract One of the greatest disturbing global health problems is antibiotic-resistant bacterial infections, which have rendered numerous currently used antibiotics ineffective. Thus, the feasibility of chitosan-coated deformable liposomes (C-Lips) containing dicloxacillin (DLX) were evaluated for their efficacy against methicillin-resistant Staphylococcus aureus (MRSA) strains, which are resistant to beta lactam antibiotics. DLX-loaded liposomes (DLX-Lip) were prepared by a lipid film hydration method and then chitosan (CS) coated (C-DLX-Lip) by the electrostatic deposition method. Both DLX-Lips and C-DLX-Lips showed a particle size distribution with a nano-range and a narrow polydispersity index (PDI). After CS coating, the zeta potential was shifted from negative to positive value. The DLX entrapment efficiency (EE) and drug loading (DL) were 62% and 5.6% for C-DLX-Lips compared to 38% and 3.1% for DLX-Lip, respectively. The in vitro release profile of C-DLX-Lips possessed a slow release behavior. Moreover, the DLX-Lips and C-DLX-Lips demonstrated an enhanced anti-MRSA activity. These results revealed that DLX-Lips and C-DLX-Lips may serve as promising carriers for DLX to increase the efficacy against MRSA, which offers considerably clinical value for long-term use of DLX. Highlights • Chitosan-coated deformable liposomes containing dicloxacillin were evaluated for its efficacy against MRSA. • Dicloxacillin-loaded liposomes were prepared by a lipid film hydration method and then coated by electrostatic deposition method. • The in vitro release profile of C-DLX-Lips possessed a slow release behavior. • The DLX-Lips and C-DLX-Lips demonstrated an enhanced anti-MRSA activity. [ABSTRACT FROM AUTHOR]