Formulation and characterization of antibiotic drug loaded aquasome for the topical application.

Aim: This study aimed to develop a topical antibiotic drug delivery system using aquasomes for enhanced treatment of skin and soft tissue infections (SSTIs). Materials & methods: Cephalothin was loaded into aquasomes using a multi-step process and optimized using design of experiment. The aquasomes were characterized for FT-IR, SEM and zeta potential analysis. Entrapment efficacy, In vitro drug release studies, antibacterial assays and stability study was performed to evaluate the efficacy of the formulated aquasomes. Results & conclusion: The formulated cephalothin-loaded aquasomes exhibited stable properties, controlled drug release and significant antibacterial activity against bacteria. This proves that the developed aquasome-based delivery system has the potential for sustained treatment of SSTIs.

Cephalothin is a medicine that helps fight bacteria, but it doesn't work well on the skin because it does not come in a gel form. We created a special way, called a magic vehicle, to help the medicine reach the skin better. Infections on the skin and in soft tissues, caused by germs. We found that our new way of giving the medicine is small, strong and fights germs very well. This could be a great way to treat skin infections and help people feel better.

Dose regimen optimization of cephalothin for surgical prophylaxis against Staphylococcus aureus and coagulase negative staphylococci in dogs by pharmacokinetic/pharmacodynamic modeling.

First generation cephalosporins such cephalothin of cefazolin are indicated for antimicrobial prophylaxis for clean and clean contaminated surgical procedures because its antimicrobial spectrum, relative low toxicity and cost. Anesthesia and surgery could alter the pharmacokinetic behavior of different drugs administered perioperative by many mechanisms that affect distribution, metabolism or excretion processes. Intravenous administration of the antimicrobial within 30 and 60 min before incision is recommended in order to reach therapeutic serum and tissue concentrations and redosing is recommended if the duration of the procedure exceeds two half-life of the antimicrobial. To the author's knowledge there are no pharmacokinetic studies of cephalothin in dogs under anesthesia/surgery conditions. The aim of this study was (1) to evaluate the pharmacokinetics of cephalothin in anesthetized dogs undergoing ovariohysterectomy by a nonlinear mixed-effects model and to determine the effect of anesthesia/surgery and other individual covariates on its pharmacokinetic behavior; (2) to determine the MIC and conduct a pharmacodynamic modeling of time kill curves assay of cephalothin against isolates of Staphylococcus spp. isolated from the skin of dogs; (3) to conduct a PK/PD analysis by integration of the obtained nonlinear mixed-effects models in order to evaluate the antimicrobial effect of changing concentrations on simulated bacterial count; and (4) to determine the PK/PD endpoints and PK/PDco values in order to predict the optimal dose regimen of cephalothin for antimicrobial prophylaxis in dogs. Anesthesia/surgery significantly reduced cephalothin clearance by 18.78%. Based on the results of this study, a cephalothin dose regimen of 25 mg/kg q6h by intravenous administration showed to be effective against Staphylococcus spp. isolates with MIC values ≤2 µg/mL and could be recommended for antimicrobial prophylaxis for clean surgery in healthy dogs.

Cephalotin Versus Dicloxacillin for the Treatment of Methicillin-Susceptible Staphylococcus aureus Bacteraemia: A Retrospective Cohort Study.

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.

Rational dosage regimens for cephalothin and cefazolin using pharmacokinetics and pharmacodynamics analysis in healthy horses.

BACKGROUND: First-generation cephalosporins have good activity against gram-positive bacteria and are extensively used in horses. There are few reports of pharmacokinetics and pharmacodynamics (PK/PD) analysis of cephalosporins in horses. OBJECTIVE: To optimise the dosages of the two first-generation cephalosporins cephalothin (CET) and cefazolin (CEZ) in horses using PK/PD concepts. STUDY DESIGN: Experimental study with single administration. METHODS: Drug plasma concentrations following a single intravenous (i.v.) administration of 22 mg/kg bodyweight (bwt) CET in 12 horses and of 10 mg/kg bwt CEZ in six horses were measured using LC-MS/MS. Data were modelled using a nonlinear mixed effect modelling followed by Monte Carlo simulations. Minimum inhibitory concentrations (MICs) against Streptococcus zooepidemicus and Staphylococcus aureus isolated from horses were determined by the microbroth dilution method. RESULTS: The percentages of CET and CEZ binding to serum proteins were 19.9% ± 8.4% and 15.2% ± 8.5% respectively. For both CET and CEZ, the MIC90 against S. zooepidemicus was 0.12 mg/L and against S. aureus was 0.5 mg/L. For CET, to achieve a probability of target attainment (PTA) of 90% for a PK/PD target of a free serum plasma concentration exceeding the MIC90 for 40% of the dosing interval, an empirical CET dosage regimen of 22 mg/kg bwt q8h and 22 mg/kg bwt q4h i.v. administration were required for S. zooepidemicus and S. aureus respectively. For CEZ, the corresponding dosage regimens were 10 mg/kg bwt q12h and 10 mg/kg bwt q8h. MAIN LIMITATIONS: Small sample size only in healthy horses. CONCLUSIONS: For CET, more frequent administration than that currently recommended (22 mg/kg bwt q6-12h) is required to empirically control S. aureus infection in horses. For CEZ, less frequent administration compared to the dosage regimen currently proposed (10-22 mg/kg bwt q6h) could control S. zooepidemicus and S. aureus infections in horses.

Análise da eficácia entre as cefalosporinas da 1. e 4. geração em cepas de Pseudomonas aeruginosa / Analysis of the efficacy enters the cephalosporins of 1st and 4th generation in strains of Pseudomonas aeruginosa

Objetivo ­ Verificar a resistência antibacteriana em cepas de Pseudomonas aeruginosa das Unidades de Tratamento Intensio (UTI's) do Hospital 28 de agosto, Hospital Universitário Francisca Mendes e Hospital e Pronto Socorro João Lúcio Pereira Machado. Métodos ­ A partir de 12 cepas de Pseudomonas aeruginosa foi realizado o teste de Concentração Inibitória Mínima (CIM), para verificar a suscetibilidade as cefalosporinas, de acordo com Clinical and Laboratory Standards Institute ­ CLSI. Resultados ­ Dentre os 12 isolados, 8 (67%) apresentaram resistência na concentração superior a 256 µg/mL na cefalosporina da 1ª geração (cefalotina); quanto a cefalosporina da 4ª geração (cefepima), cerca de 4 (33%) das amostras isoladas foram sensíveis ao antibiótico. Conclusão ­ Elevadas amostras foram resistentes a cefalotina, enquanto na cefepima, mostraram sensibilidade.

Objective ­ To verify the antibacterial resistance in Pseudomonas aeruginosa strains of the Intensive Care Units (ICUs) of Hospital 28 de agosto, Hospital Universitário Francisca Mendes and Hospital e Pronto Socorro João Lúcio Pereira Machado. Methods ­ From 12 strains of Pseudomonas aeruginosa, the Minimum Inhibitory Concentration (MIC) test was performed to verify the susceptibility of cephalosporins, according to the Clinical and Laboratory Standards Institute - CLSI. Results ­ Among the 12 isolates, 8 (67%) presented resistance in the concentration above 256 µg/mL in cephalosporin of the first generation (cephalothin); for cephalosporin of the 4th generation (cefepime), about 4 (33%) of the isolated samples were sensitive to the antibiotic, at the concentration of 4 µg/mL. Conclusion ­ High samples were resistant to cephalothin, whereas in cefepime, they showed sensitivity

Review for Analytical Methods for the Determination of Sodium Cephalothin.

Infections are the second leading cause of global morbidity and mortality, therefore it is highly important to study the antimicrobial agents such as cephalosporins. Cephalothin, an antimicrobial agent that belongs to the class of cephalosporins, has bactericidal activity and it is widely used in the Brazilian health system. In literature, some analytical methods are found for the identification and quantification of this drug, which are essential for its quality control, which ensures maintaining the product characteristics, therapeutic efficacy and patient's safety. The aim of this article is to review the available information on analytical methods for cephalothin. Thus, this study presents a literature review on cephalothin and the analytical methods developed for the analysis of this drug in official and scientific papers. It is essential to note that most of the developed methods used toxic and hazardous solvents, which makes necessary industries and researchers choose to develop environmental-friendly techniques, which will contribute to the harmonization of science, human, and environmental health.

Escherichia coli OxyS RNA triggers cephalothin resistance by modulating the expression of CRP-associated genes.

Antibiotics have been one of the most successful forms of therapy in medicine. However, the efficiency of antibiotics is compromised by the emergence of antibiotic-resistant pathogens. To reduce antibiotic resistance, complete understanding of bacterial tactics to defend themselves against antibiotics is necessary. Small-noncoding RNAs (sRNAs) modulate gene expression by base-pairing with multiple target mRNAs. Cellular levels of Hfq-dependent sRNAs influence antibiotic resistance by modulating expression of specific target genes; therefore, such sRNAs could be a good tool to identify target mRNAs that modulate antibiotic susceptibility and may themselves be used as druggable molecules. Here, we report the identification of genes and pathways associated with OxyS RNA-mediated cephalothin resistance using phenotypic and expression analyses of OxyS-regulated genes identified by RNA-seq, literature mining, or predictions. From our studies we found that the differential expression of 27 OxyS-regulated genes was involved in cephalothin susceptibility. Among them, 17 gene knockouts showed resistance to the drug and nine from them is associated with cAMP receptor protein (CRP), a transcriptional dual regulator in E. coli. Moreover, levels of OxyS and OxyS-modulated genes (cycA and cysH) were also altered in multidrug-resistant (MDR) E. coli strains. Together, our data suggest that OxyS extensively modulates gene expression in multiple pathways to develop cephalothin resistance. In addition, OxyS and its regulated target genes, either individually or in combination, could be used as molecular markers and targets for the identification and eradication of cephalothin-resistant strains.

Cephalexin susceptibility breakpoint for veterinary isolates: Clinical Laboratory Standards Institute revision.

The Clinical and Laboratory Standards Institute (CLSI) uses cephalothin as the class representative for testing veterinary isolates for susceptibility to other first-generation cephalosporins, including cephalexin. We examined replacing cephalothin with cephalexin because cephalexin is used more often clinically. Bacterial isolates were obtained from dogs and cats from a national surveillance program. CLSI testing methods were used to determine the MIC for 4 cephalosporins used in veterinary medicine. Cephalexin clinical breakpoints for canine isolates were established by using published pharmacokinetic data and Monte Carlo simulations to calculate the probability of target attainment (PTA). For 1,112 Staphylococcus pseudintermedius isolates, the mode, MIC50, and MIC90 were 1, 2, and 64 µg/mL, respectively, for cephalexin, and ≤0.06, 0.12, and 2 µg/mL for cephalothin. Susceptibility of S. pseudintermedius from 2011 to 2014 did not change for the 4 cephalosporins tested. Only 4.3% of the penicillin-binding protein 2a-positive S. pseudintermedius isolates had MIC values ≤2 µg/mL for cephalexin, but 66.3% of these isolates had MIC values ≤2 µg/mL for cephalothin. There were also discrepancies between cephalexin and cephalothin for other bacteria tested, but the largest difference was for S. pseudintermedius, with a MIC difference of 4 doubling dilutions. Cephalexin interpretive categories (breakpoints) of ≤2 µg/mL (susceptible), 4 µg/mL (intermediate), and ≥8 µg/mL (resistant) were established for isolates obtained from dogs. Cephalothin should not be used for susceptibility testing of cephalexin for veterinary bacterial pathogens, and canine-specific breakpoints should be used for testing susceptibility. Breakpoints determined using the methods described herein for the interpretive categories will be added to future CLSI tables to reflect this recommendation.

Cephalothin is not a reliable surrogate marker for oral cephalosporins in susceptibility testing of Enterobacteriaceae causing urinary tract infection.

Vitek® 2 (bioMérieux) is a widely used commercial antimicrobial susceptibility test (AST) system. AST-N244 card includes cephalothin as first-generation cephalosporin. We compared the cephalothin susceptibility results obtained with Vitek® 2 AST-N244 to those obtained by broth microdilution (BMD) and disk diffusion (DD) for 212 urinary Enterobacteriaceae. We also evaluated the differences between cefazolin and cephalothin susceptibility results. The overall performance of Vitek® 2 for cephalothin testing was 74.5% and 76.4% category agreement compared to BMD and DD, respectively; 84.4% essential agreement; very major errors 15.2% and 11.1% compared to BMD and DD; major errors 0% compared to both methods; and minor errors 22.2% and 21.7% compared to BMD and DD. Regarding correlation between cephalothin and cefazolin, the differences observed were statistically significant (P<0.0001) for the 167 Escherichia coli included (39.5% cephalothin susceptible versus 92.2% cefazolin susceptible by BMD; 41.9% cephalothin susceptible versus 93.4% cefazolin susceptible by DD). Vitek® 2 should provide cefazolin instead of cephalothin as a surrogate marker for oral cephalosporins on the urinary AST-244 cards in order to follow the CLSI (2016) recommendations.

Synthesis, characterization and antibacterial activity of a tridentate Schiff base derived from cephalothin and sulfadiazine, and its transition metal complexes.

Metal(II) coordination compounds of a cephalothin Schiff base (H2L) derived from the condensation of cephalothin antibiotic with sulfadiazine were synthesized. The Schiff base ligand, mononuclear [ML(H2O)3] (M(II)=Mn,Co,Ni,Zn) complexes and magnetically diluted dinuclear copper(II) complex [CuL(H2O)3]2 were characterized by several techniques, including elemental and thermal analysis, molar conductance and magnetic susceptibility measurements, electronic, FT-IR, EPR and (1)H NMR spectral studies. The cephalothin Schiff base ligand H2L behaves as a dianionic tridentate NOO chelating agent. The biological applications of complexes have been studied on two bacteria strains (Escherichia coli and Staphylococcus aureus) by agar diffusion disc method.

Structural basis for the ß-lactamase activity of EstU1, a family VIII carboxylesterase.

EstU1 is a unique family VIII carboxylesterase that displays hydrolytic activity toward the amide bond of clinically used ß-lactam antibiotics as well as the ester bond of p-nitrophenyl esters. EstU1 assumes a ß-lactamase-like modular architecture and contains the residues Ser100, Lys103, and Tyr218, which correspond to the three catalytic residues (Ser64, Lys67, and Tyr150, respectively) of class C ß-lactamases. The structure of the EstU1/cephalothin complex demonstrates that the active site of EstU1 is not ideally tailored to perform an efficient deacylation reaction during the hydrolysis of ß-lactam antibiotics. This result explains the weak ß-lactamase activity of EstU1 compared with class C ß-lactamases. Finally, structural and sequential comparison of EstU1 with other family VIII carboxylesterases elucidates an operative molecular strategy used by family VIII carboxylesterases to extend their substrate spectrum.

Cephalothin susceptibility testing as class representative for oral cephalosporins: is it time to move on?

Based on current epidemiologic and resistance trends, we propose reconsideration of the use of cephalothin susceptibility to predict susceptibility to oral narrow-spectrum cephalosporins among Enterobacteriaceae, particularly in predicting cephalexin susceptibility for urinary tract isolates.

A case of cephalothin-associated urolithiasis.

We present a case of osteomyelitis requiring prolonged intravenous cephalothin complicated by symptomatic calcium oxalate urocalculi formation. Patients on long-term ß-lactam antibiotics with lower urinary tract symptoms may have urolithiasis rather than a urinary tract infection.