First-generation Cephalosporin Antibiotic Research Articles

Single-Dose First-Generation Cephalosporin for Extremity Gunshot Wounds Offers Sufficient Infection Prophylaxis

Antibiotic prophylaxis for extremity gunshot wounds (GSWs) is highly variable. The objective of the present study is to quantify the adherence rate to a protocol for single-dose cephalosporin prophylaxis for extremity GSWs and the impacts on post-injury infection rates. We reviewed patients presenting to a level 1 trauma center with an extremity gunshot wound between 2019 and 2021. Infection rates were compared for patients following the protocol or not, and for patients presenting before or after the protocol’s implementation. Overall, 94% of patients received antibiotic treatment at presentation, but only 34% followed the single-dose antibiotic protocol. The rate of protocol adherence increased from 15% to 39% after the protocol was implemented in the hospital in January 2020 (p = 0.081). Infection rates were not different before and after the protocol implementation (25% vs. 18%, p = 0.45). Infection rates were also not different between patients who did and did not follow the protocol (15% vs. 20%, p = 0.52). The implementation of a single-dose cephalosporin protocol increased adherence to the protocol in a level 1 trauma center without increasing infection rates. These findings support conservative treatment along with a single dose of first-generation cephalosporin antibiotic for uncomplicated extremity GSWs in order to decrease healthcare costs without compromising infection risk.

Meta-Analysis of Clinical Trials Comparing Cefazolin to Cefuroxime, Ceftriaxone, and Cefamandole for Surgical Site Infection Prevention.

Surgical site infections are among the most prevalent and costly healthcare-associated infections, resulting in poor patient outcomes and even death. Cefazolin is a first-generation cephalosporin antibiotic that is widely used for surgical prophylaxis in a variety of surgical disciplines. Although previous studies showed that cefazolin is effective in preventing surgical site infections, other agents, such as cefuroxime and ceftriaxone, were used excessively for surgical patients. The present analysis included only clinical trials comparing the efficacy of cefazolin to cefuroxime, ceftriaxone, and cefamandole in lowering SSIs using PubMed, Google Scholar, and ClinicalTrials.gov. Review Manager software (RevMan version 5.4) was used to conduct the meta-analyses. A total of 12,446 patients were included in the study. Among these patients, 6327 patients received cefazolin and 6119 patients received cefamandole, cefuroxime, or ceftriaxone. Our analysis showed that cefazolin is as effective as cefuroxime, cefamandole, and ceftriaxone in preventing surgical site infections. Hence, our findings have provided evidence for the use of cefazolin before surgeries because of its efficacy, as previous studies showed that it is inexpensive and safer than other agents.

The use of first-generation cephalosporin antibiotics, cefalexin and cefradine, is not associated with induction of simulated Clostridioides difficile infection.

ObjectivesThe use of broad-spectrum cephalosporins is associated with induction of Clostridioides difficile infection (CDI). Recent knowledge on the importance of the healthy microbiota in preventing pathogen colonization/outgrowth highlights the caution needed when prescribing broad-spectrum antibiotics. The use of historical narrow-spectrum antibiotics, such as first-generation cephalosporins, is gaining increased attention once more as they have a reduced impact on the microbiota whilst treating infections. Here, the effects of two first-generation cephalosporins, compared with a third-generation cephalosporin, on the human microbiota were investigated and their propensity to induce simulated CDI.MethodsThree in vitro chemostat models, which simulate the physiochemical conditions of the human colon, were seeded with a human faecal slurry and instilled with either narrow-spectrum cephalosporins, cefalexin and cefradine, or a broad-spectrum cephalosporin, ceftriaxone, at concentrations reflective of colonic levels.ResultsInstillation of cefalexin was associated with reduced recoveries of Bifidobacterium and Enterobacteriaceae; however, Clostridium spp. recoveries remained unaffected. Cefradine exposure was associated with decreased recoveries of Bifidobacterium spp., Bacteroides spp. and Enterobacteriaceae. These changes were not associated with induction of CDI, as we observed a lack of C. difficile spore germination/proliferation, thus no toxin was detected. This is in contrast to a model exposed to ceftriaxone, where CDI was observed.ConclusionsThese model data suggest that the minimal impact of first-generation cephalosporins, namely cefalexin and cefradine, on the intestinal microbiota results in a low propensity to induce CDI.

Aerosol inhalation delivery of cefazolin in mice: Pharmacokinetic measurements and antibacterial effect

Aerosol inhalation delivery of cefazolin, a broad-spectrum first-generation cephalosporin antibiotic, was investigated. Inhalation system based on ultrasonic nebulizer was developed for the generation of dry cefazolin aerosol within mean particle diameter range 0.5–3.0 μm and mass concentration 0.01–3 μg/cm3. Pharmacokinetic measurements were carried out for the aerosolized form of cefazolin delivered in mice using nose-only chamber. Cefazolin concentrations in blood serum and in the lungs of mice were measured as a function of time by means of high performance liquid chromatography. Body-delivered dose depending on particle size, concentration and inhalation time as well as other pharmacokinetic parameters were determined. The antibacterial effect of aerosolized cefazolin was assessed through the aerosol inhalation treatment of mice infected with Klebsiella pneumoniae. Survival rate for infected mice after the treatment with cefazolin aerosol demonstrated high antibacterial efficiency of the inhalation delivery of cefazolin in comparison with intraperitoneal delivery.

Molecular structure and quantum descriptors of cefradine by using vibrational spectroscopy (IR and Raman), NBO, AIM, chemical reactivity and molecular docking.

This study aims to investigate the structural and vibrational features of cefradine (the first-generation cephalosporin antibiotic) based on spectroscopic experiments and theoretical quantum chemical approach. The fundamental structural aspects of cefradine have been examined based on optimized geometry, spectroscopic behavior, intermolecular interaction, chemical reactivity, intramolecular hydrogen bonding, and molecular docking analysis. The most stable minimum energy conformer of the title molecule was identified by performing a one-dimensional potential energy surface scan along the rotational bonds at B3LYP/6-311++G (d,p) level of theory. The vibrational features of the molecule and information about the coupled modes were predicted. The chemical reactivity and stability of all the possible conformers of cefradine were estimated based on the HOMO-LUMO energy gap and NBO approach. The overall picture of accumulation of charges on individual atoms of the molecule was predicted by molecular electrostatic potential (MEP) surface map which in turn identifies the nucleophilic and electrophilic region or sites. The quantitative analysis of electrophilicity and nucleophilicity indices was done by Hirshfeld charge analysis and it was found that N8 atom is the most prominent site for nucleophilic attack while C14 atom is feasible for electrophilic attack. QTAIM study has also been performed to investigate the nature and strength of hydrogen bonding interactions. Besides, molecular docking studies were performed to examine the active binding residues of the target.

Development of a Broad-Specific Competitive ELISA for First-Generation Cephalosporin Antibiotics in Animal-Derived Foods Samples.

The abuse of antibiotics, such as the cephalosporins in livestock and aquaculture productions, usually causes the widespread antibiotic resistance due to their growth-promoting effects. In this study, cephalexin was chosen as the hapten molecule to prepare a broad-spectrum rabbit polyclonal antibody for cephalosporin antibiotics. The obtained antibody exhibited broad cross-reactivity ranging from 0.05% to 100% with 10 cephalosporins. Based on this antibody, we developed a broad-specific indirect competitive ELISA (ic-ELISA) for cefalexin, cefradine, cefadroxil and cefazolin with the half maximal inhibitory concentration (IC50) ranging from 0.72 to 2.99ng/mL in working buffer. For animal-derived food samples with spiked cephalosporins, the ic-ELISA exhibited an excellent recovery ranging from 72.3% to 95.6%. To verify the accuracy of this proposed ic-ELISA, its detection performance was evaluated utilizing the high-performance liquid chromatography with satisfactory results. This study confirmed that: firstly, the prepared antibody can be used as a class-specific recognition element to develop immunoassays for cephalosporin antibiotics; and secondly, the developed ic-ELISA provided a new tool for broad-spectrum detection of first-generation cephalosporins in animal-derived foods.

The anti-inflammatory potential of cefazolin as common gamma chain cytokine inhibitor

A continuing quest for specific inhibitors of proinflammatory cytokines brings promise for effective therapies designed for inflammatory and autoimmune disorders. Cefazolin, a safe, first-generation cephalosporin antibiotic, has been recently shown to specifically interact with interleukin 15 (IL-15) receptor subunit α (IL-15Rα) and to inhibit IL-15-dependent TNF-α and IL-17 synthesis. The aim of this study was to elucidate cefazolin activity against IL-2, IL-4, IL-15 and IL-21, i.e. four cytokines sharing the common cytokine receptor γ chain (γc). In silico, molecular docking unveiled two potential cefazolin binding sites within the IL-2/IL-15Rβ subunit and two within the γc subunit. In vitro, cefazolin decreased proliferation of PBMC (peripheral blood mononuclear cells) following IL-2, IL-4 and IL-15 stimulation, reduced production of IFN-γ, IL-17 and TNF-α in IL-2- and IL-15-treated PBMC and in IL-15 stimulated natural killer (NK) cells, attenuated IL-4-dependent expression of CD11c in monocyte-derived dendritic cells and suppressed phosphorylation of JAK3 in response to IL-2 and IL-15 in PBMC, to IL-4 in TF-1 (erythroleukemic cell line) and to IL-21 in NK-92 (NK cell line). The results of the study suggest that cefazolin may exert inhibitory activity against all of the γc receptor-dependent cytokines, i.e. IL-2, IL-4, IL-7, IL-9, IL-15 and IL-21.

Pharmacophore guided discovery of small-molecule interleukin 15 inhibitors

Upregulation of interleukin 15 (IL-15) contributes directly i.a. to the development of inflammatory and autoimmune diseases. Selective blockade of IL-15 aimed to treat rheumatoid arthritis, psoriasis and other IL-15-related disorders has been recognized as an efficient therapeutic method. The aim of the study was to identify small molecules which would interact with IL-15 or its receptor IL-15Rα and inhibit the cytokine's activity. Based on the crystal structure of IL-15Rα·IL-15, we created pharmacophore models to screen the ZINC database of chemical compounds for potential IL-15 and IL-15Rα inhibitors. Twenty compounds with the highest predicted binding affinities were subjected to in vitro analysis using human peripheral blood mononuclear cells to validate in silico data. Twelve molecules efficiently reduced IL-15-dependent TNF-α and IL-17 synthesis. Among these, cefazolin - a safe first-generation cephalosporin antibiotic - holds the highest promise for IL-15-directed therapeutic applications.

Nimbolide from Azadirachta indica and its derivatives plus first-generation cephalosporin antibiotics: a novel drug combination for wound-infecting pathogens

We evaluate the in vitro efficacy of nimbolide, desacetylnimbin, and the amide derivatives of nimbolide in combination with first-generation cephalosporin antibiotics against major wound-associated bacterial pathogens.

Safety and Efficacy of Cefazolin Sodium in the Management of Bacterial Infection and in Surgical Prophylaxis

Cefazolin sodium is a first-generation cephalosporin antibiotic and has been used worldwide since the early 1970s. It is used for the treatment of bacterial infections in various organs, such as the respiratory tract, skin and skin structure, genital tract, urinary tract, biliary tract, and bone and joint infections. It has also been used for septicemia due to susceptible gram-positive cocci (except Enterococcus), some gram-negative bacilli including E. coli, Proteus, and Klebsiella may be susceptible, and for perioperative prophylaxis. After the introduction of penicillins and other cephalosporins, occasional outbreaks of methicillin-resistant Staphylococcus aureus were noted. As a result, vancomycin use was increased; however, very recently and most alarmingly, vancomycin-resistant strains have been described. In this setting, to avoid the risk of the development of vancomycin-resistant strains further, vancomycin use should be curtailed. In consideration of this historical background, the appropriate use of antibiotics, such as dosage, dosage intervals, and the duration of administration is required not only for the protection of patients’ health but also for the prevention of the development of drug resistance. Cefazolin has been used in clinical practice for about 40 years, and a large body of evidence has been accumulated, and its efficacy and safety are well established compared with other antibiotics. Therefore, cefazolin has been chosen as a first-line anti-microbial for prophylaxis after various surgical procedures, including cardiovascular surgery, hysterectomy, arthroplasty and so on. Based on these facts, especially for the prophylaxis of surgical site infections, the first-generation cephalosporin, cefazolin, is now being “re-visited”.

Administration of Cefazolin Prior to Skin Incision Is Superior to Cefazolin at Cord Clamping in Preventing Postcesarean Infectious Morbidity: A Randomized, Controlled Trial

Antibiotic prophylaxis can lower the risk of postcesarean infection by up to 75%. First-generation cephalosporin antibiotics are most commonly used, and usually are given after the umbilical cord is clamped. This prospective, double-blind, randomized trial was carried out to learn whether administering antibiotic before skin incision might be superior to traditional prophylaxis. The 357 participants, women scheduled to have cesarean delivery, received 1 g of cefazolin in 50 mL of normal saline either 15 to 60 minutes before the incision or at the time of cord clamping. The 2 groups were demographically similar. Total infectious morbidity was less frequent in the study group to a statistically significant degree, with a relative risk (RR) of 0.4 (95% confidence interval [CI], 0.18–0.87). Adjusting for demographic and clinical variables associated with risk of infection did not alter this outcome. Endomyometritis also was significantly less frequent in the study group (RR, 0.2; 95% CI, 0.15–0.94). Wound infections were more prevalent in the control group but not significantly so. One study patient had pneumonia, and one control subject, pyelonephritis. No significant group differences were found for neonatal sepsis, total length of stay, metabolic acidosis, or work-up for sepsis. Although admissions to neonatal intensive care also were similar in the 2 groups, infants whose mothers received antibiotic preoperatively spent significantly fewer days in the intensive care facility. Infectious organisms associated with neonatal sepsis were similar in the 2 groups, and antibiotic-resistant organisms were not more frequent in either group. The investigators recommend that women requiring cesarean section receive antibiotic prophylaxis preoperatively. Because cost is not increased and infectious morbidity is likely to be reduced, this probably will be a cost-effective approach.

Strategies for the determination of cefazolin in plasma and microdialysis samples by short-end capillary zone electrophoresis.

Capillary zone electrophoresis was employed to determine cefazolin, a first-generation cephalosporin antibiotic, in plasma and microdialysis samples from patients. To shorten the analysis, the samples were injected from the short end of the capillary, resulting in a separation time of < 3 min. Due to a high ionic strength of the biological matrices it was necessary to optimize the stacking conditions. For microdialysis samples a 1:10 dilution with water before injection was sufficient to obtain good peak shape. For plasma samples a protein removal step was required to obtain clean electropherograms and a good peak shape. Acetonitrile was used as precipitant resulting in an enhanced sample stacking in comparison to water dilution. The disadvantage of using acetonitrile was severe evaporation loss making quantitation impossible. A self-sealing film was used to seal each individual sample vial to suppress evaporation during long-term sequences. The calibration curves for spiked plasma and cefazolin in Ringer's solutions were linear in the range from 2-500 and 2.5-100 microg/mL, respectively. Limits of detection were 1.0 and 2.0 microg/mL in plasma and microdialysis samples, respectively. The assay was successfully applied to plasma and microdialysis samples obtained in vivo from the interstial space fluid of subcutaneous adipose and muscle tissue of patients undergoing cardiac surgery.