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PubMed2004

Reversible coma secondary to cefepime neurotoxicity.

OBJECTIVE: To describe a case of cefepime neurotoxicity associated with acute renal failure that resulted in nonconvulsive status epilepticus. CASE SUMMARY: A 66-year-old woman with acute myeloid leukemia had fever on the third day of the initial chemotherapy cycle. Empiric antibiotic treatment with cefepime 2 g every 8 hours was started; fluconazole and vancomycin were subsequently added due to the persistence of fever. Ten days after initiation of cefepime, the patient developed acute renal failure followed by altered consciousness (Glasgow coma scale 6) associated with nonconvulsive status epilepticus. Cefepime was discontinued. Epileptiform activity in the electroencephalogram disappeared with clonazepam, and the patient regained consciousness 48 hours after cefepime withdrawal. DISCUSSION: Acute renal impairment combined with the use of cefepime may account for nonconvulsive status epilepticus. An objective causality assessment revealed that the adverse event was probably due to cefepime. Cefepime's neurotoxic effects derive from high serum concentrations resulting from decreased renal clearance, increased unbound antibiotic, and blood-brain barrier dysfunction during uremia. CONCLUSIONS: The combination of cefepime treatment and acute renal failure may induce drug-related neurotoxicity. Nonconvulsive status epilepticus frequently passes unnoticed in severely ill patients without a history of epilepsy. This disorder should be included in the list of potential causes of coma. In this patient, early detection of nonconvulsive status epilepticus and withdrawal of the antibiotic resulted in full recovery.

Acute Kidney Injury↗
PubMed2004

Stability of cefepime in icodextrin peritoneal dialysis solution.

BACKGROUND: Icodextrin is a glucose polymer used as an alternative osmotic agent in peritoneal dialysis (PD) solutions. Cefepime may be a suitable antibiotic for the treatment of PD-related peritonitis. The stability of cefepime in icodextrin PD solution has not been examined. OBJECTIVE: To determine the chemical stability of cefepime in icodextrin PD solution over a 7-day period. METHODS: Samples were prepared by adding cefepime HCl 1000 mg to commercially available 2.0-L bags of icodextrin 7.5% PD solution. Nine bags were prepared and stored in the following conditions: 3 under refrigeration (4 degrees C), 3 at room temperature (20 degrees C), and 3 at body temperature (37 degrees C). Study samples were drawn from each bag immediately after preparation and at predetermined intervals over the subsequent 7 days. Solutions were visually inspected for precipitation, cloudiness, or discoloration at each sampling interval. Total concentration of cefepime in dialysate fluid was determined by liquid chromatography-tandem mass spectrometry. RESULTS: Under refrigeration, a mean +/- SD of 95.7 +/-4.2% of the initial cefepime concentration remained at 168 hours (7 days). At room temperature, 92.0 +/- 17.9% remained at 48 hours. At body temperature, 92.2 +/- 4.7% remained at 4 hours. Beyond these respective time points, <90% of the initial cefepime concentrations remained. CONCLUSIONS: Pre-mixed cefepime-icodextrin PD solutions stored at room temperature were stable for up to 48 hours. However, it is recommended that these be kept refrigerated whenever possible. When refrigerated, cefepime-icodextrin solutions were found to be stable for up to 7 days. Solutions stored at body temperature were stable up to 4 hours, permitting the practice of pre-warming solutions prior to administration.

Anti-Bacterial Agents↗
PubMed2001

Susceptibility of pseudomonas aeruginosa to cefepime versus ceftazidime in patients with cystic fibrosis.

STUDY OBJECTIVES: To compare the susceptibility of respiratory cultures of Pseudomonas aeruginosa obtained from patients with cystic fibrosis to cefepime versus ceftazidime. The pattern of cumulative resistance of P aeruginosa to cefepime in patients who had received at least one treatment course of cefepime between two sputum cultures was also characterized. DESIGN: Prospective consecutive data collection. SETTING: University-affiliated cystic fibrosis clinic and medical center. PATIENTS: Eighty patients with cystic fibrosis who had at least one sputum culture positive for P aeruginosa with reported microbiologic susceptibilities to cefepime and ceftazidime. INTERVENTION: Patient data was collected and analyzed. Measurements and Main Results. Two hundred and thirty-one P aeruginosa isolates were collected over 6 months. A total of 16.4% and 8.7% of the isolates were nonsusceptible to cefepime and ceftazidime, respectively (p=0.01). In eight patients who had not received cefepime before the study period, nonsusceptibility was 11.8% and 27.2% before and after exposure to cefepime, respectively. CONCLUSIONS: Susceptibility of P. aeruginosa isolates in patients with cystic fibrosis was lower with cefepime than with ceftazidime. Follow-up surveillance to determine changes in susceptibility of P aeruginosa isolates to cefepime is warranted.

Adolescent↗
PubMedDate not supplied

[Cefepime (Maxipime) treatment efficacy in surgical patients ].

Between September and December 2001 in the "Caritas" Surgical Clinic of Bucharest has been conducted a clinical study for the efficiency of Cefepime (Maxipime) treatment in surgical patients. Introduced in therapy in the last decade of the XXth Century, Cefepime (Maxipime) is the most active 4th generation cephalosporin, due to its extended spectrum of activity and its high resistance against beta-lactamases. Cefepime (Maxipime) has a very large spectrum, including the majority of the microorganisms implicated in surgical infections: Enterobacter, Klebsiella pneumoniae/speciae, Proteus mirabilis, Bacillus fragillis, Pseudomonas aeruginosa, Serratia, Citrobacter and other Gram-negative bacilii, Gram-positive cocci (Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus pyogenes). The clinical study included 30 surgical patients, the selection criteria being the severity of the present infection or the potential risk after major (abdominal) surgery. We introduced Cefepime (Maxipime) as first choice of monotheraphy, except: severe, life threatening nosocomial infections, when we associated Cefepime (Maxipime) with aminoglycosides; failure of another antibiotheraphy schema, when we associated Cefepime (Maxipime) with aminoglycosides; suspicion of anaerobe contamination, when we associated Cefepime (Maxipime) with metronidazole. The results of our study support the utilization of Cefepime (Maxipime) as the best choice antibiotic in severe surgical infections, especially in the intensive care and surgical units. Cefepime (Maxipime) can be synergically associated with aminoglycosides and imidazoles (metronidazole).

Adult↗
PubMed1998

Activity of cefepime compared with other antibiotics against gram-positive bacteria and cefuroxime-resistant gram-negative bacteria.

BACKGROUND: Cefepime is a new, parenteral, fourth-generation antibiotic that is stable in the presence of Bush group 1 beta-lactamases. In vitro activity of cefepime, cefuroxime, ceftazidime, ciprofloxacin and imipenem against Gram-positive cocci and cefuroxime-resistant Gram-negative bacilli was studied. METHODS: The agar dilution method described by the US National Committee for Clinical Laboratory Standards was used to determine the minimum inhibitory concentrations of antibiotics tested. These included cefepime, cefuroxime, ceftazidime, ciprofloxacin and imipenem. The tested clinical isolates included Gram-positive cocci (methicillin-sensitive coagulase-negative staphylococci, methicillin-resistant coagulase-negative staphylococci, methicillin-sensitive Staphylococcus aureus, methicillin-resistant S aureus, Streptococcus pyogenes, viridans streptococci, Streptococcus pneumoniae, group D enterococci) and cefuroxime-resistant Gram-negative bacilli (Escherichia coli, Klebsiella pneumoniae, Acinetobacter spp, Pseudomonas aeruginosa, Enterobacter cloacae, Serratia marcescens, Burkholderia cepacia and Xanthomonas maltophilia). RESULTS: The activity of cefepime against most Gram-negative bacilli other than B cepacia and X maltophilia is better than that of ceftazidime. However, cefepime is less active against these Gram-negative bacilli than ciprofloxacin and imipenem. The activity of cefepime against B cepacia and X maltophilia is less than that of ceftazidime or ciprofloxacin. Among Gram-positive cocci, cefepime was active against most isolates of methicillin-sensitive staphylococci, S pyogenes, viridans streptococci and S pneumoniae. However, cefepime has poor activity against methicillin-resistant S aureus and enterococci. CONCLUSIONS: Due to its extended spectrum of activity, cefepime has potential use as suitable empiric monotherapy for the treatment of a variety of community- and hospital-acquired infections.

Cefepime↗
PubMed2005

Clinical implications of extended spectrum beta-lactamase (ESBL) producing Klebsiella species and Escherichia coli on cefepime effectiveness.

OBJECTIVE: To determine the affect of ESBL production among Klebsiella species and Escherichia coli on cefepime effectiveness. METHODS: This was a retrospective, case-controlled study comparing the clinical and microbiologic responses of patients receiving cefepime for ESBL producing Klebsiella species or E. coli from a non-urine source with matched controls receiving cefepime for non-ESBL strains. Cases with ESBLs were included if they received monotherapy and were clinically evaluable. Non-ESBL controls were matched in a 2:1 ratio based on age, infection site, intensive care unit (ICU) stay, pathogen species and date of hospitalization. RESULTS: Ten patients receiving cefepime for ESBLs were matched to 20 controls. Most patients received cefepime 1g q12h. Patients receiving cefepime for an ESBL infection were 9.7 (95% CI: 1.4-68.8) and 28.5 (95% CI: 2.6-306.6) times as likely to have an unsuccessful clinical and microbiological response compared with those with a non-ESBL infection. The presence of an ESBL did not have a statistically significant effect on all cause or infection-related mortality. CONCLUSION: These data indicate that ESBL production among non-urinary Klebsiella species and E. coli negatively affected cefepime effectiveness. Further studies are required to evaluate if higher doses of cefepime may improve responses in ESBLs that are initially susceptible.

Adult↗
PubMed1995

Cefepime.

Because of the popularity of some third-generation cephalosporins, emergence of resistant organisms (e.g., selected Enterobacteriaceae) that produce inducible and extended-spectrum beta-lactamases has been a problem. Cefepime's twice-a-day dosage schedule and enhanced activity against Enterobacteriaceae and gram-positive organisms give it several advantages over older drugs. The clinical efficacy of cefepime has been demonstrated in comparative and noncomparative trials in the United States and Europe. Cefepime with twice-daily dosing has been useful in the treatment of lower respiratory tract infections, urinary tract infections, skin and skin structure infections, and in serious infection, including those with associated bacteremia. Cefepime is comparable to ceftazidime in clinical and bacteriologic response rates when both agents are administered three times a day in febrile neutropenic patients. Cefepime is also active against organisms that show resistance to other agents. Several studies have shown that cefepime retains its activity against E. cloacae and E. coli strains resistant to other cephalosporins and against many strains of P. aeruginosa resistant to ceftazidime. Cefepime exhibits a low level of cross-resistance with third-generation cephalosporins and a low propensity for selection of resistant mutants and offers a low potential for the induction of bacterial resistance, which complicates the course of many patients treated with single-agent third-generation therapy. Cefepime should be used in place of ceftazidime based on resistance potential, activity against resistant organisms, and cost.

Bacterial Infections↗
PubMed2003

Neutropenia in patients receiving long-term cefepime therapy for osteomyelitis.

The frequency of neutropenia in patients receiving long-term cefepime therapy for osteomyelitis compared with that in patients receiving other antimicrobials was studied. A comparative case review was conducted of home infusion patients receiving cefepime and patients receiving other antimicrobials for osteomyelitis. All courses of antimicrobial therapy for osteomyelitis between January 2001 and December 2002 were evaluated. The duration of prescribed therapy was approximately six weeks. Weekly laboratory tests included complete blood counts with differential. A total of 134 courses of antimicrobial therapy were reviewed (13 courses of cefepime therapy in 12 patients and 121 courses of therapy with other i.v. antimicrobials in 120 patients). Eight (62%) of the cefepime courses resulted in neutropenia, compared with none in the courses of other antimicrobials. Neutropenia was detected after 17-30 days of cefepime therapy. Blood counts returned to normal within one week of cefepime discontinuation. Eight of 13 courses of extended therapy with i.v. cefepime for osteomyelitis resulted in neutropenia, compared with none of 121 courses of other antimicrobials. Clinicians should exercise extreme caution when prescribing cefepime for longer than 14 days.

Adolescent↗
PubMed1998

Cefepime versus imipenem-cilastatin as empirical monotherapy in 400 febrile patients with short duration neutropenia. CEMIC (Study Group of Infectious Diseases in Cancer).

This open, comparative, randomized, multicentre equivalence study compared cefepime 2 g bd and imipenem-cilastatin 1 g tds (50 mg/kg/day) as empirical monotherapy for febrile episodes in a homogeneous cohort of cancer patients with short duration neutropenia following chemotherapy for solid tumour, lymphoma or myeloma. The study was conducted in 17 French anti-cancer centres in 1995 and 1996. Response to monotherapy was assessed 7 days after treatment and was based on resolution of fever and signs and symptoms, eradication of pathogens, absence of new infection, relapse, and death of infectious origin, without addition of other antibiotics. Patients were treated for a minimum of 4 days. Of the 400 episodes randomized, 344 (86%) were evaluable for efficacy. Patient characteristics were comparable between treatment groups. Success of monotherapy was observed in 79% of episodes with cefepime and 72% with imipenem-cilastatin (equivalence, P <0.0001). The response rate for microbiologically documented infections was 66% with cefepime and 61% with imipenem-cilastatin (bacteraemic episodes: 63% for cefepime; 44% for imipenem-cilastatin). A second antibiotic (usually a glycopeptide) was added in 20% and 21% of the cases, respectively. Overall, the response to therapy, with or without an additional antibiotic, was 95% (cefepime) and 90% (imipenem-cilastatin). Survival was similar in both groups (95% and 98%, respectively). Cefepime treatment was better tolerated, with 9% of the patients experiencing related intercurrent events compared with 19% in the imipenem-cilastatin group (P = 0.003). Nausea/vomiting was significantly more frequent in the imipenem-cilastatin group (15%) than in the cefepime group (5%; P = 0.001). Cefepime monotherapy was as effective as, and better tolerated than, imipenem-cilastatin in the empirical treatment of fever during short duration neutropenia.

Antineoplastic Agents↗
PubMed1999

Treatment of community-acquired pneumonia in the elderly: the role of cefepime, a fourth-generation cephalosporin.

In a prospective, multicentre double-blind trial, 151 patients over the age of 65 years were randomly assigned to receive either cefepime 2 g every 12 h for a minimum of 3 days and up to 14 days or ceftriaxone 1 g every 12 h for a minimum of 3 days and up to 14 days. Antibiotics were maintained until 48 h after fever had resolved; no other antibiotics were permitted. The average age in each group exceeded 77 years and significant co-morbidity was found in the majority of patients. The mean total duration of therapy was 5.8+/-2.4 days for the cefepime group and 6.7+/-2.7 days for the ceftriaxone group (P = 0.06). The clinical success rate at the end of therapy was 79.1% with cefepime and 75.4% with ceftriaxone (P = 0.62). At the end of follow-up, 91.7% of the cefepime-treated patients and 86.5% of the ceftriaxone patients had a satisfactory clinical response (P = 0.38). In 35 bacteriological evaluable patients, potential pathogens were eradicated in all but one patient receiving cefepime. Seven patients in each group died during the study period but in each case the death was unrelated to study drug. The commonest side-effect was diarrhoea (cefepime, five patients; ceftriaxone, two patients). The clinical and microbiological efficacy of cefepime is similar to that of ceftriaxone in elderly patients with community-acquired pneumonia requiring hospitalization. Cefepime is an appropriate choice for the treatment of community-acquired respiratory tract infections in the elderly.

Aged↗
PubMed2006

High-dose cefepime as an alternative treatment for infections caused by TEM-24 ESBL-producing Enterobacter aerogenes in severely-ill patients.

This study evaluated retrospectively the efficacy of treatment with cefepime vs. a carbapenem, in combination with amikacin or ciprofloxacin, for seriously-ill patients infected with ESBL-producing Enterobacter aerogenes who were admitted to an intensive care unit. Forty-four episodes of infection were investigated in 43 patients: 21 treated with cefepime; 23 with a carbapenem. The two treatment groups did not differ statistically in terms of age, APACHE II scores, and infection sites, but the average duration of antibiotic exposure was significantly shorter in the cefepime group (8.5 days vs. 11.4 days; p 0.04). Clinical improvement was seen in 62% of patients receiving cefepime vs. 70% of patients receiving a carbapenem (p 0.59). Bacteriological eradication was achieved in 14% of patients receiving cefepime vs. 22% of patients receiving a carbapenem (p 0.76). The 30-day mortality rates related to infection were 33% in the cefepime group and 26% in the carbapenem group (p 0.44). Thus, outcome parameters did not differ significantly between the two groups. Nevertheless, a statistically significant increase in failure to eradicate ESBL-producing E. aerogenes was observed as the MICs of cefepime rose (p 0.017). Pulsed-field gel electrophoresis revealed three distinct clones, but one predominant clone harbouring the bla(TEM-24) gene was associated with most (42/44) of the episodes of infection. It was concluded that cefepime may be an alternative agent for therapy of severe infections caused by TEM-24 ESBL-producing E. aerogenes, although further studies are required to confirm these observations.

Adult↗
PubMed2001

Extension of resistance to cefepime and cefpirome associated to a six amino acid deletion in the H-10 helix of the cephalosporinase of an Enterobacter cloacae clinical isolate.

Enterobacter cloacae CHE, a clinical strain with overproduced cephalosporinase was found to be highly resistant to the new cephalosporins, cefepime and cefpirome (MICs> or =128 microg ml(-1)). The strain was isolated from a child previously treated with cefepime. The catalytic efficiency of the purified enzyme with the third-generation cephalosporins, cefepime and cefpirome, was 10 times higher than that with the E. cloacae P99 enzyme. This was mostly due to a decrease in K(m) for these beta-lactams. The clinical isolate produced large amounts of the cephalosporinase because introduction of the ampD gene decreased ampC expression and partially restored the wild-type phenotype. Indeed, MICs of cefepime and cefpirome remained 10 times higher than those for a stable derepressed clinical isolate (OUDhyp) transformed with an ampD gene. Sequencing of the ampC gene showed that 18 nucleotides had been deleted, corresponding to the six amino acids SKVALA (residues 289--294). According to the crystal structure of P99 beta-lactamase, this deletion was located in the H-10 helix. The ampR-ampC genes from the clinical isolates CHE and OUDhyp were cloned and expressed in Escherichia coli JM101. The MICs of cefpirome and cefepime of E. coli harboring ampC and ampR genes from CHE were 100--200 times higher than those of E. coli harboring ampC and ampR genes from OUDhyp. This suggests that the deletion, confirmed by sequencing of the ampC gene, is involved in resistance to cefepime and cefpirome. However, the high level of resistance to cefepime and cefpirome observed in the E. cloacae clinical isolate was due to a combination of hyperproduction of the AmpC beta-lactamase and structural modification of the enzyme. This is the first example of an AmpC variant conferring resistance to cefepime and cefpirome, isolated as a clinical strain.

Amino Acid Sequence↗
PubMed2005

Pharmacodynamics of cefepime alone and in combination with various antimicrobials against methicillin-resistant Staphylococcus aureus in an in vitro pharmacodynamic infection model.

Treatment options for gram-positive resistant bacteria are limited; therefore, efforts to evaluate therapy options in the critical care population are warranted. Cefepime has broad-spectrum activity against gram-negative and gram-positive organisms. We have previously demonstrated that the combination of cefepime with vancomycin, linezolid, or quinupristin-dalfopristin had an improved or enhanced effect against methicillin-resistant Staphylococcus aureus (MRSA). We investigated various regimens of cefepime alone and in combination against two clinical MRSA isolates (R2481 and R2484) in an established in vitro pharmacodynamic model. Human pharmacokinetic regimen simulations were as follows: cefepime, 2 g every 8 h (q8h) (C8) and 12 h (C12), continuous-infusion 2-g loading dose followed by 4 g alone or in combination with gentamicin and tobramycin (1.0 or 2.0 [G1 and G2 or TB1 and TB2] mg/kg of body weight q12h and 5.0 [G5 or TB5] mg/kg q24h), arbekacin (ARB) (100 mg q12h), linezolid (LIN) (600 mg q12h), tigecycline (TIG) (100 mg q24h), or daptomycin (DAP) (6 mg/kg q24h) for 48 h. The MICs for cefepime, gentamicin, tobramycin, ARB, LIN, TIG, and DAP for the two clinical MRSA isolates (R2481 and R2484) were 4 and 4, 0.25 and 0.5, 128 and 0.5, 0.5 and 0.125, 2 and 4, 0.25 and 0.25, and 0.0625 and 0.125 microg/ml, respectively. At 48 h, combinations of C12 and C8 plus ARB, G1, or G5 (range, -2.05- to -4.32-log(10) decrease) demonstrated enhanced lethality against R2481 (resistant to tobramycin) (P < 0.05). A similar relationship was demonstrated against R2484 with cefepime plus ARB, gentamicin, or tobramycin (range, -2.05- to -3.63-log(10) decrease) (P < 0.05). A 99.9% kill was achieved with cefepime plus aminoglycoside combinations as early as 2 h and maintained throughout the 48-h period. TIG was antagonistic when combined with C12 against both isolates. DAP alone achieved 99.9% kill for up to 48 h for both isolates and was the most active agent against R2481 and R2484 (-2.89- and -3.61-log(10) decrease at 48 h); therefore, combination therapy did not enhance lethality. Overall, the most potent combinations noted were cefepime in combination with low- and high-dose aminoglycosides. Further investigations with combination therapies are warranted.

Anti-Bacterial Agents↗
PubMed2005

Efficacy of cefepime and imipenem in experimental murine pneumonia caused by porin-deficient Klebsiella pneumoniae producing CMY-2 beta-Lactamase.

Previous studies have shown decreased in vitro activity of zwitterionic cephalosporins and carbapenems against porin-deficient Klebsiella pneumoniae expressing a plasmid-mediated AmpC-type beta-lactamase (PACBL). The in vitro and in vivo activities of cefepime and imipenem were evaluated against the porin-deficient strain K. pneumoniae C2 and its CMY-2-producing derivative [K. pneumoniae C2(pMG248)]. The MICs (in micrograms/milliliter) of cefepime and imipenem against K. pneumoniae C2 were 0.125 and 0.25, respectively, while the corresponding values against K. pneumoniae C2(pMG248) were 8 and 16. Cefepime showed a greater inoculum effect than imipenem against both strains. Imipenem showed a significant postantibiotic effect (>2 h) against K. pneumoniae C2(pMG248) at 1x, 2x, 4x, 6x, and 8x MIC. The maximum concentrations of drug in serum of cefepime and imipenem in a pneumonia model using mice were 124.1 and 16.9 mug/ml, respectively. DeltaT/MIC for K. pneumoniae C2 and C2(pMG248) were 1.29 h and 0.34 h for imipenem and 2.96 h and 1.27 h for cefepime. Both imipenem (30 mg/kg of body weight every 3 h) and cefepime (60 mg/kg every 4 h), administered for 72 h, increased the survival rate (86.6% and 100%) compared with untreated control animals (26.6%, P < 0.003) infected with K. pneumoniae C2. For the CMY-2-producing strain, imipenem, but not cefepime, increased the survival rate compared to the controls (86.6% and 40% versus 40%, P < 0.01). Bacterial concentration of the lungs was significantly decreased by both antimicrobials. In conclusion, imipenem was more active in terms of survival than cefepime for the treatment of murine pneumonia caused by a porin-deficient K. pneumoniae expressing PACBL CMY-2.

Animals↗
PubMed1996

Cefepime: a fourth-generation parenteral cephalosporin.

OBJECTIVE: To review the chemistry, microbiology, pharmacokinetics, therapeutic efficacy, adverse effect profile, drug interactions, dosing, and administration of cefepime, a new fourth-generation parenteral cephalosporin. DATA SOURCES: A MEDLINE search of the available literature, including clinical trials and reviews, was performed. Abstracts presented at recent scientific conferences and current publications were also reviewed. DATA SELECTION: In vitro and preclinical data were included, as well as data from Phase II and III clinical trials. DATA SYNTHESIS: Cefepime is an extended-spectrum parenteral cephalosporin antibiotic active in vitro against a broad spectrum of gram-positive and gram-negative aerobic bacteria. The gram-positive spectrum is similar to that of cefotaxime, the gram-negative spectrum is similar to that of ceftazidime, and many, though not all, organisms resistant to these two agents remain susceptible to cefepime, prompting the fourth-generation designation. Cefepime has a high affinity for penicillin-binding proteins and, due to its zwitterionic configuration, rapidly penetrates outer-membrane porin channels of bacteria. Beta-lactamases appear to have a low affinity for the drug. Cefepime has a decreased propensity to induce beta-lactamases compared with other beta-lactam antibiotics. Cefepime has a pharmacokinetic disposition similar to that of other renally eliminated cephalosporins, with a half-life of approximately 2 hours. Cefepime has demonstrated clinical efficacy against a variety of infections, including urinary tract infections, pneumonia, and skin and skin structure infections. Cefepime is generally well tolerated.

Cefepime↗
PubMed2005

Effect of cefepime on startle amplitude and prepulse inhibition of startle reflex in rats: manipulation of GABAA receptor function with midazolam.

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.

Animals↗
PubMed2003

Neurotoxicity induced by Cefepime in a very old hemodialysis patient.

Neurotoxicity is an unusual complication of cephalosporin therapy. Only few cases of neurotoxicity induced by Cefepime have been described and probably the frequency of Cefepime-induced status epilepticus is underestimated. We report a case of an 82 year-old male, ESRD patient on chronic hemodialysis program affected by pneumonia, who received a treatment with intravenous Cefepime (1 g/day) and developed a seizure 4 days after the starting antibiotic therapy. Cefepime-induced neurotoxicity was suspected and its administration was immediately discontinued. In order to increase Cefepime clearance a hemodialysis session was urgently started and an improvement of his conscious level was observed. On the following day, after a second hemodialysis session his clinical condition and the status of neurotoxicity were completely recovered. The patient was discharged from the hospital in stable clinical condition one week later. At variance with the cases previously reported, the daily dose of Cefepime administrated to our patient was 50% lower and respected drug prescription dosage. Thus, we speculate on the hypothesis that advanced age of our patient and metabolic encephalopathy induced by chronic uremia made him more sensitive to the neurotoxicity induced by the drug. In conclusion, our case suggests that, in very old patients on long-term hemodialysis, it should be considered, to avoid neurotoxicity, to monitor the clinical neurological status, to use Cefepime at lower dosage than that allowed in patients with severe renal impairment (1 g/day) and, when possible, to evaluate Cefepime plasma levels. However, in these patients, other agents of the same class should be considered such as Cefotaxime and Ceftriaxone which are characterized by both an hepatic and renal excretion. In alternative to cephalosporins, antibiotics with the same action spectrum in the absence of neurological toxicity (i.e. Meropenem) should be recommended.

Aged↗
PubMed1989

Comparison of the in vitro and in vivo antibacterial activities of cefepime (BMY-28142) with ceftazidime, cefuzonam, cefotaxime and cefmenoxime.

Cefepime (BMY-28142), a new semisynthetic cephalosporin, was evaluated for in vitro and in vivo antibacterial activities in comparison with ceftazidime, cefuzonam, cefotaxime and cefmenoxime. Cefepime showed a well-balanced, broad spectrum of activity against a number of clinical isolates collected in Japan. The activity of cefepime against Gram-positive bacteria was several times greater than that of ceftazidime, nearly comparable to cefotaxime and cefmenoxime, and slightly weaker than cefuzonam. Against Enterobacteriaceae, cefepime showed superior activity to the reference cephalosporins against Proteus inconstans, Providencia rettgeri, Morganella morganii, Citrobacter freundii and Enterobacter cloacae. The activity of cefepime against Pseudomonas aeruginosa was nearly comparable to that of ceftazidime. Cefotaxime, cefuzonam and cefmenoxime were substantially less active against P. aeruginosa. Cefepime was more stable than cefuzonam, cefotaxime and cefmenoxime to various types of beta-lactamases from Gram-negative bacteria. The high in vitro activity of cefepime was reflected in its in vivo efficacy against experimental infections in normal and immuno-suppressed mice. Cefepime was the most effective among the cephalosporins tested against four Gram-negative bacterial infections.

Animals↗