Effect Of Cefepime Research Articles

Efficacy of cephalosporins against enterobacteria isolated from patients with chronic osteomyelitis

Long-term antibiotic therapy, as well as inappropriate use of drugs in the treatment of osteomyelitis, can lead to the appearance of pan-resistant strains. The existing antibiotic prophylaxis regimens for purulent-septic complications are outdated and need to be adjusted. In this regard, it is necessary to monitor the resistance of microorganisms in order to identify ineffective antibacterial drugs. To analyze the resistance profiles of Enterobacteriaceae isolated from patients with chronic osteomyelitis to cephalosporin drugs over a three-year period. The resistance profiles of 912 clinical strains of Enterobacteriaceae were analyzed: Klebsiella pneumoniae (n=349), Proteus sp. (n=208), Escherichia coli (n=176), Enterobacter cloacae (n=179) for the period from 2018-2020 to cephalosporin drugs. In 2018, 66.2% of Enterobacteriaceace were resistant to the 1st generation cephalosporins, in 2019 - 78.7%, in 2020 - 79.5%. Generation II cephalosporins were most active against Proteus sp. bacteria, but a decrease in clinical effect was observed by 2020. Among the third generation cephalosporins in 2018, cefotaxime was most active, but in 2020 the number of resistant strains doubled and amounted to 86.3%. Ceftazidime was active against 47.1% of Enterobacteriaceae isolates in 2018, in 2019 - 45% of strains, in 2020 - 37.2% of bacterial strains. High activity of ceftriaxone was noted only in 2018 against Proteus sp. Preparations of the IV generation in 2018 showed the highest activity against bacteria of the genus Proteus, the least - against bacteria K. pneumoniae. In the period from 2019-2020, a significant decrease in the effectiveness of cefepime was observed.The monitoring of the resistance profiles to antibiotics of the cephalosporin series revealed their low efficacy against Enterobacteriaceae isolated from wounds and fistulas of patients with chronic osteomyelitis, which shows the inexpediency of their empirical use.

Effect of cefepime on hematological, immunological and oxidant/antioxidant parameters in rats experimentally infected with E. coli ATCC 25922

Objective: To evaluate the effect of cefepime on hematological changes, immunological disorders and hepatic oxidative damage in rats experimentally infected with E.coli ATCC 25922. Design: Randomized controlled experimental study. Animals: Thirty-two adult male albino rats weighting150-200 g. Procedures: Rats used for this study were randomly assigned into 4 equal groups: the control one, E.coli infected group (1×108CFU/I/P/once), the cefepime treated group (45 mg/kg bw/I/M/day) for 5 days and the E.coli infected group that treated with cefepime 24h after bacterial inoculation as previously described. Hematological and immunological parameters, liver function biomarkers and hepatic oxidative stress and antioxidant markers were determined. Results: Our result revealed that E.coli infection induced a significant elevation in the erythrocytes count, hemoglobin concentration, PCV% and total leukocytic count (TLC) (P < 0.05). In the same respect, liver function biomarkers, serum glucose, total cholesterol, and triglyceride levels as well hepatic malondialdehyde (MDA), nitric oxide (NO), TNF-α, IL-10, and lysozyme activity were significantly increased compared to the control rats (P < 0.05). In contrast, hepatic reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) were decreased significantly (P < 0.05). Cefepime treatment in E.coli + CFPM group reduced the elevated eythrogram, TLC and liver function biomarkers. Cefepime also ameliorated the oxidative damage and inflammatory response induced by E.coli infection. Conclusion and clinical relevance: Cefepime is safe when administered in a fixed-dose and possess antioxidant that contributes to improve efficacy against adverse effect induced by E.coli ATCC 25922 infection.

Impact of cefepime on hematological, immunological and oxidant/antioxidant parameters in rats experimentally infected with E. coli ATCC 25922

Objective: To evaluate the effect of cefepime on hematological changes, immunological disorders and hepatic oxidative damage in rats experimentally infected with E.coli ATCC 25922. Design: Randomized controlled experimental study. Animals: Thirty-two adult male albino rats weighting150-200 g. Procedures: Rats used for this study were randomly assigned into 4 equal groups: the control one, E.coli infected group (1×108CFU/I/P/once), the cefepime treated group (45 mg/kg bw/I/M/day) for 5 days and the E.coli infected group that treated with cefepime 24h after bacterial inoculation as previously described. Hematological and immunological parameters, liver function biomarkers and hepatic oxidative stress and antioxidant markers were determined. Results: Our result revealed that E.coli infection induced a significant elevation in the erythrocytes count, hemoglobin concentration, PCV% and total leukocytic count (TLC) (P < 0.05). In the same respect, liver function biomarkers, serum glucose, total cholesterol, and triglyceride levels as well hepatic malondialdehyde (MDA), nitric oxide (NO), TNF-α, IL-10, and lysozyme activity were significantly increased compared to the control rats (P < 0.05). In contrast, hepatic reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) were decreased significantly (P < 0.05). Cefepime treatment in E.coli + CFPM group reduced the elevated eythrogram, TLC and liver function biomarkers. Cefepime also ameliorated the oxidative damage and inflammatory response induced by E.coli infection. Conclusion and clinical relevance: Cefepime is safe when administered in a fixed-dose and possess antioxidant that contributes to improve efficacy against adverse effect induced by E.coli ATCC 25922 infection.

Impact of cefepime on hematological, immunological and oxidant/antioxidant parameters in rats experimentally infected with E. coli ATCC 25922

Objective: To evaluate the effect of cefepime on hematological changes, immunological disorders and hepatic oxidative damage in rats experimentally infected with E.coli ATCC 25922. Design: Randomized controlled experimental study. Animals: Thirty-two adult male albino rats weighting150-200 g. Procedures: Rats used for this study were randomly assigned into 4 equal groups: the control one, E.coli infected group (1×108CFU/I/P/once), the cefepime treated group (45 mg/kg bw/I/M/day) for 5 days and the E.coli infected group that treated with cefepime 24h after bacterial inoculation as previously described. Hematological and immunological parameters, liver function biomarkers and hepatic oxidative stress and antioxidant markers were determined. Results: Our result revealed that E.coli infection induced a significant elevation in the erythrocytes count, hemoglobin concentration, PCV% and total leukocytic count (TLC) (P < 0.05). In the same respect, liver function biomarkers, serum glucose, total cholesterol, and triglyceride levels as well hepatic malondialdehyde (MDA), nitric oxide (NO), TNF-α, IL-10, and lysozyme activity were significantly increased compared to the control rats (P < 0.05). In contrast, hepatic reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) were decreased significantly (P < 0.05). Cefepime treatment in E.coli + CFPM group reduced the elevated eythrogram, TLC and liver function biomarkers. Cefepime also ameliorated the oxidative damage and inflammatory response induced by E.coli infection. Conclusion and clinical relevance: Cefepime is safe when administered in a fixed-dose and possess antioxidant that contributes to improve efficacy against adverse effect induced by E.coli ATCC 25922 infection.

Impact of cefepime on hematological, immunological and oxidant/antioxidant parameters in rats experimentally infected with E. coli ATCC 25922

Objective: To evaluate the effect of cefepime on hematological changes, immunological disorders and hepatic oxidative damage in rats experimentally infected with E.coli ATCC 25922. Design: Randomized controlled experimental study. Animals: Thirty-two adult male albino rats weighting150-200 g. Procedures: Rats used for this study were randomly assigned into 4 equal groups: the control one, E.coli infected group (1×108CFU/I/P/once), the cefepime treated group (45 mg/kg bw/I/M/day) for 5 days and the E.coli infected group that treated with cefepime 24h after bacterial inoculation as previously described. Hematological and immunological parameters, liver function biomarkers and hepatic oxidative stress and antioxidant markers were determined. Results: Our result revealed that E.coli infection induced a significant elevation in the erythrocytes count, hemoglobin concentration, PCV% and total leukocytic count (TLC) (P < 0.05). In the same respect, liver function biomarkers, serum glucose, total cholesterol, and triglyceride levels as well hepatic malondialdehyde (MDA), nitric oxide (NO), TNF-α, IL-10, and lysozyme activity were significantly increased compared to the control rats (P < 0.05). In contrast, hepatic reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) were decreased significantly (P < 0.05). Cefepime treatment in E.coli + CFPM group reduced the elevated eythrogram, TLC and liver function biomarkers. Cefepime also ameliorated the oxidative damage and inflammatory response induced by E.coli infection. Conclusion and clinical relevance: Cefepime is safe when administered in a fixed-dose and possess antioxidant that contributes to improve efficacy against adverse effect induced by E.coli ATCC 25922 infection.

Impact of cefepime on hematological, immunological and oxidant/antioxidant parameters in rats experimentally infected with E. coli ATCC 25922

Objective: To evaluate the effect of cefepime on hematological changes, immunological disorders and hepatic oxidative damage in rats experimentally infected with E.coli ATCC 25922. Design: Randomized controlled experimental study. Animals: Thirty-two adult male albino rats weighting150-200 g. Procedures: Rats used for this study were randomly assigned into 4 equal groups: the control one, E.coli infected group (1×108CFU/I/P/once), the cefepime treated group (45 mg/kg bw/I/M/day) for 5 days and the E.coli infected group that treated with cefepime 24h after bacterial inoculation as previously described. Hematological and immunological parameters, liver function biomarkers and hepatic oxidative stress and antioxidant markers were determined. Results: Our result revealed that E.coli infection induced a significant elevation in the erythrocytes count, hemoglobin concentration, PCV% and total leukocytic count (TLC) (P < 0.05). In the same respect, liver function biomarkers, serum glucose, total cholesterol, and triglyceride levels as well hepatic malondialdehyde (MDA), nitric oxide (NO), TNF-α, IL-10, and lysozyme activity were significantly increased compared to the control rats (P < 0.05). In contrast, hepatic reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) were decreased significantly (P < 0.05). Cefepime treatment in E.coli + CFPM group reduced the elevated eythrogram, TLC and liver function biomarkers. Cefepime also ameliorated the oxidative damage and inflammatory response induced by E.coli infection. Conclusion and clinical relevance: Cefepime is safe when administered in a fixed-dose and possess antioxidant that contributes to improve efficacy against adverse effect induced by E.coli ATCC 25922 infection.

Effect of Cefepime on Neurotoxicity Development in Critically Ill Adults With Renal Dysfunction

Pharmacodynamic and pathophysiologic changes in critically ill adults receiving cefepime may increase the risk of adverse events. What is the impact of cefepime exposure on neurotoxicity development in critically ill adults with renal dysfunction? Critically ill adults with creatinine clearance< 60mL/min who received cefepime for≥ 48 hours between January 1, 2014 and July 31, 2018 were evaluated for cefepime-associated neurotoxicity (CAN) development. Higher- and lower-dose cefepime exposure groups stratified by moderate (≥ 8g vs< 8g in first 48 hours) or severe (≥ 4g vs< 4g in first 48 hours) renal dysfunction were compared. Between-group comparisons were performed using Fisher exact tests. CAN-free survival was evaluated using Kaplan-Meier curves and log-rank tests. Cefepime total dose in the first 48 hours was greater in the higher-dose cefepime group (3.7 ± 1.6g vs7.7 ± 2.2 g; P< .001). Cefepime-associated neurotoxicity occurred infrequently in both lower- (n= 108) and higher-dose (n= 92) cefepime groups (4%vs10%, OR 2.82, 95%CI, 0.84-9.48, P= .093). The frequencies of cefepime-associated neurotoxicity were similar between lower- and higher-dose cefepime groups when moderate renal dysfunction subgroups were compared (5%vs7%, OR 1.42, 95%CI, 0.34-5.92, P= .72) and numerically greater in the higher-dose cefepime group in the severe renal dysfunction subgroup (0 vs16%, P= .064). Times to cefepime-associated neurotoxicity development and resolution were similar between lower- and higher-dose groups. Durations of CAN-free survival were similar between lower- and higher-dose groups. Most patients who developed cefepime-associated neurotoxicity displayed altered mental status (n= 12, 92%). Cefepime-associated neurotoxicity is an uncommon occurrence in critically ill adults. Patients with severe renal dysfunction receiving higher-dose cefepime may be at greater risk of cefepime-associated neurotoxicity, although this requires additional investigation.

Cefepime vs. meropenem for moderate-to-severe pneumonia in patients at risk for aspiration: An open-label, randomized study

BackgroundTreatment of aspiration pneumonia is an important problem due to aging of populations worldwide. However, the effectiveness of cefepime in aspiration pneumonia has not yet been evaluated. AimTo compare the clinical efficacy and safety of cefepime and meropenem in patients with moderate-to-severe aspiration pneumonia. MethodsIn this open-label, randomized study, either cefepime 1 g or meropenem 0.5 g was administered intravenously every 8 h to patients with moderate-to-severe community-acquired or nursing-home acquired pneumonia at risk for aspiration for an average of 10.5 days. The primary outcome was the clinical response rate at the end of treatment (EOT) in the validated per-protocol (VPP)-population. Secondary outcomes were clinical response during treatment (days 4 and 7) and at the end of study (EOS) in the VPP-population, and survival at day 30 in the modified intention-to-treat (MITT)-population. ResultsThere was no difference between the groups in the primary or secondary outcomes or safety. Significant improvement was observed in each group on day 4. ConclusionCefepime is as effective and safe as meropenem in the treatment of moderate-to-severe aspiration pneumonia. Clinical trials identifierUMIN000001349.

Nephrotoxicity of cefepime: A new cephalosporin antibiotic in rats

Objectives:To investigate the nephrotoxic effect and biochemical alterations induced by cefepime in rats.Materials and Methods:Cefepime was administered intramuscularly at doses of 45, 90 and 180 mg/kg b.wt. once daily for 5 consecutive days. The serum and urine samples were used for quantitative determination of urea, creatinine, glucose, total protein, calcium, sodium and potassium. The histopathological examination of kidney tissues was performed 1, 4 and 8 days after the last dose of cefepime administration.Results:Cefepime induced a significant increase in the total amount of urine per day, urea and creatinine concentration in the serum and urine and significant decrease in their clearance. Cefepime also caused a significant gluocosuria and proteinuria and significant decrease in their serum concentrations. The effect of cefepime on serum and urine concentrations of calcium, sodium and potassium were also determined. Cefepime injection in the three tested doses caused renal tubular, glomerular and vascular changes. The severity of these changes was dose dependent. In conclusion, these results suggest a possible contribution of cefepime in the nephrotoxicity and biochemical alterations, especially at high doses. Therefore, the renal functions should be monitored during the cefepime therapy.

In Vitro Interaction between Cefepime and Amoxicillin-Clavulanate against Extended-Spectrum β-Lactamase-Producing Escherichia coli

We read with interest the article by Chopra et al. ([1][1]) suggesting that empirical therapy with cefepime for bloodstream infections due to extended-spectrum-β-lactamase (ESBL)-producing Enterobacteriaceae is associated with excess mortality. The effectiveness of cefepime would be compromised by

Comparison of efficiency of intravitreal ceftazidime and intravitreal cefepime in the treatment of experimental Pseudomonas aeruginosa endophthalmitis

In this study, we evaluated the efficiency of cefepime in the treatment of experimental Pseudomonas aeruginosa endophthalmitis. We compared the findings with the standard dose of ceftazidime (1 mg/0.1 ml). Thirty-six New-Zealand White rabbits were divided into 6 equal groups and were treated with different methods (Group 1 = sham, Group 2 = 0.5 mg/0.1 ml cefepime, Group 3 = 1 mg/0.1 ml cefepime, Group 4 = 2 mg/0.1 ml cefepime, Group 5 = 1 mg/0.1 ml ceftazidime, Group 6 = control). The eyes of rabbits in each group were examined clinically on 1st, 3rd, and 6th day of the experiment. At 6th day, 0.1 ml vitreous humor aspirates were obtained and plated for quantification on the blood agar and the results were expressed as colony-forming unit/ml. Subsequently, the eyeballs were enucleated and the histopathological evaluation was performed. Our findings denoted beneficial effects of cefepime in treatment groups (especially, in Groups 3 and 4). Intravitreal cefepime may be an alternative drug in the treatment of P. aeruginosa endophthalmitis.

In vitro effects of sulbactam combinations with different antibiotic groups against clinical Acinetobacter baumannii isolates

Treatment of multidrug resistant (MDR) Acinetobacter baumannii infections causes some problems as a result of possessing various antibacterial resistance mechanisms against available antibiotics. Combination of antibiotics, acting by different mechanisms, is used for the treatment of MDR bacterial infections. It is an important factor to determine synergy or antagonism between agents in the combination for the constitution of effective therapy. The study aimed to determine in vitro interactions interpreted according to calculated fractional inhibitory concentration (FIC) index between sulbactam and ceftazidime, ceftriaxone, cefepime, ciprofloxacin, gentamicin, meropenem, tigecycline, and colistin. Ten clinical isolates of A. baumannii were tested for determination of synergistic effects of sulbactam with different antimicrobial combinations. Minimal inhibitory concentration (MIC) values of both sulbactam and combined antibiotics decreased 2- to 128-fold. Synergy and partial synergy were determined in combination of sulbactam with ceftazidime and gentamicin (FIC index: ≤0·5 or >0·5 to <1) and MIC values of both ceftazidime and gentamicin for five isolates fell down below the susceptibility break point. Similarly, MIC value of ciprofloxacin for six ciprofloxacin resistant isolates was determined as below the susceptibility break point in combination. However, all isolates were susceptible to colistin and tigecycline, MIC values of both were decreased in combination with sulbactam. Although synergistic and partial synergistic effects were observed in the combination of sulbactam and ceftriaxone, all isolates remained resistant to ceftriaxone. The effect of cefepime–sulbactam combination was synergy in five, partial synergy in one and indifferent in four isolates. Meropenem and sulbactam showed a partial synergistic effect (FIC index: >0·5 to <1) in three, an additive effect (FIC index: 1) in one and an indifferent effect (FIC index: >1–2) in six isolates. Antagonism was not determined in any combination for clinical A. baumannii isolates in the study. In conclusion, sulbactam is a good candidate for combination treatment regimes for MDR A. baumannii infections.

Effect of Cefepime in Patients with Cirrhosis and Spontaneous Acid Infection

Aims : In this study in cirrhosis patients having spontaneous ascites infection (SAI) the investigation of the activity of cefepime being a fourth generation cephalosporin was aimed. Method : 19 patients diagnosed as cirrhosis and having acid infection were taken into the study. Cefepime doses were given to all patients having SAI by adjusting according to the clearance of creatinine, in intervals of 12 hours, in 2 gram as parenterally. Cell counting was made in acid liquid on the 1st, 3rd and 5th days. In the patients who had reproduction in acid liquid culture, antibiogram was made with cefepime and other antibiotics. Result : Age average of patients was 55 years (between 42-73 years). Cirrhosis was secondary to hepatitis B virus infection in 10 patients, to hepatitis C virus infection in 7 patients and to autoimmune hepatitis in 2 patients. On the first day the average cell number in the ascites was 5077/mm3 (between 530-12400/mm3), PMNL number was 3861/mm3 (between 320-9600/mm3). On the third day the average cell number in the ascites was 1847/mm3 (between 300-7680/mm3) and PMNL number was 1025/mm3 (between 120-3840/mm3) (p< 0.001). Fifth day ascites liquid the average cell number was 548/mm3 (between 160--1600/mm3) and PMNL number was 267/mm3 (between 80-620/mm3) (p< 0.001). The cefepime resistance in antibiogram was observed only on one patient against E.coli strain. Conclusions: Cefepime, which is a fourth generation cephalosropin, was found out effective in SAI developing on cirrhotic ground.

Effect of cefepime on startle amplitude and prepulse inhibition of startle reflex in rats: Manipulation of GABA-A receptor function with midalozam

Disruption of prepulse inhibition (PPI) of startle response is manifested in schizophrenia and Huntington's disease among other neuropsychiatric disorders characterized by sensorimotor gating deficit. Antagonism of GABAA receptor function was documented to reduce PPI response. However, whether GABAA antagonism reduces PPI response is yet to be established because of contradicting reports. Cefepime is one of the fourth-generation cephalosporins documented to antagonize GABAA receptor function. This study investigated the effect of intramuscular injection of cefepime (45 and 90 mg/kg) twice daily for three consecutive days on both PPI of acoustic startle response and acoustic startle amplitude in rats. The effect of administration of the GABAA receptor agonist midazolam (1 mg/kg, i.p.) in conjunction with cefepime on PPI response and startle amplitude was also investigated. Results showed that administration of both dose levels of cefepime caused PPI deficit. Treatment of animals with midazolam in conjunction with cefepime reversed the effect of the lower dose, but not the higher one, on PPI of startle response without affecting startle amplitude in both dose levels. Results of this study, therefore, support the view that GABAA antagonism reduces PPI response. It is also concluded that antagonism of GABAergic transmission may be involved in the effect of the lower dose of cefepime on PPI response. Other mechanisms may mediate the effect of the higher dose of cefepime on PPI response. Clinical investigations are needed to determine the consequence of using cefepime in disorders of sensorimotor gating.

Effects of Cefepime, Cefixime and Ceftibuten on Murine Gut Colonization by Candida albicans

Crl:CD1(ICR) BR mice were fed chow containing Candida albicans or regular chow. Both groups were subsequently given either antibiotics or normal saline. Stool cultures were performed before, at the end of treatment and 1 week after treatment, to determine the effect on the stool yeast concentration. Candida-colonized mice treated with cefepime, cefixime or ceftibuten had higher (however not significantly) counts of the yeast in their stools than control Candida-fed mice treated with saline. A group of Candida-fed mice were treated with ceftriaxone, which is known to increase the yeast stool concentration significantly and served as positive control. Mice fed regular chow and treated with the study drugs or saline did not have any yeasts in their stools. Dissemination of Candida did not occur.

A non-comparative study of the efficacy and tolerance of cefepime in combination with amikacin in the treatment of severe infections in patients in intensive care

Patients in intensive care units (ICUs) are at increased risk of developing nosocomial infections. This is of special concern in the immunocompromised patient, particularly with regard to multiresistant pathogens. We evaluated the effectiveness of cefepime 2 g bd in combination with amikacin 7.5 mg/kg bd for the treatment of severe bacterial infection in 118 ICU patients, including 113 patients with nosocomial lower respiratory tract infections (LRTI) (mean age, 51 years). Ninety-six per cent (108/113) of the LRTI patients required respiratory assistance and 12% (14/113) had associated septicaemia/bacteraemia. Eighty-four per cent (95/113) had clinical signs of sepsis and 35% (39/113) had features of septic shock. The mean Simplified Acute Physiologic Score (SAPS) was 12 at inclusion. Seventy-nine patients with LRTI were clinically and bacteriologically evaluable. The causative pathogens were representative of those usually isolated in ICUs: Staphylococcus aureus (19%); Pseudomonas aeruginosa (14%); and Klebsiella, Enterobacter and Serratia spp. (17%). The clinical cure rate was 86% (68/79) while the pathogen eradication rate was 91% (107/117). Of the patients with associated septicaemia/bacteraemia, 89% (8/9) of the pathogens were eliminated. Cefepime-amikacin combination therapy was well tolerated; two patients discontinued treatment due to rashes. Combination therapy with cefepime 2 g bd and amikacin 7.5 mg/kg bd appears safe and effective for the treatment of nosocomial pneumonia in patients hospitalized in ICUs. Further comparative controlled studies are justified.

The Effect of Cefepime on Some Immune ParametersIn Vitro:Lack of Interference with Mitogen-Induced Lymphoproliferation, Immunoglobulin Synthesis, IFN-Gamma and IL-2 Secretion and IL-2 Receptor Expression

The possible interference of the novel antibiotic cefepime (CPE) with some functions of the immune system was investigated in vitro. Peripheral blood mononuclear cells (PBMC) cultured in the presence of drug concentrations ranging from 25 to 100 micrograms/ml normally maintained their responsiveness to polyclonal (PHA, Con A, PWM) mitogenic stimulation in regard to proliferative response, IgM and IgG synthesis and IFN-gamma and IL-2 secretory capacity. Moreover, PHA-induced expression of IL-2 receptors was comparable in PBMCs cultured in the presence or absence of CPE. Taken together, these data suggest that CPE does not interfere, at this specific level, with T- and B-cell mediated functions in vitro.