, Lagarde C The cefepime MIC distribution for P. aeruginosa is displayed in Fig. , Ericsson CD 41, 79, 80 Except for three patients with unrecorded clinical outcomes, CIN-associated symptoms improved in all cases. Do not flush down a toilet or pour down a drain unless you are told to do so. In chromosomal aberration studies, this antibiotic was positive for clastogenicity in primary human lymphocytes, but negative in Chinese hamster ovary cells. [, Ganapathy ME, Huang W, Rajan DP, Carter AL, Sugawara M, Iseki K, Leibach FH, Ganapathy V: beta-lactam antibiotics as substrates for OCTN2, an organic cation/carnitine transporter. https://clinicaltrials.gov/ct2/show/NCT03332732. Cefepime is a fourth-generation cephalosporin antibiotic. , Sahm D Carsenti-Etesse H , Flamm RK The site is secure. Read all information given to you. 2000 Jan 21;275(3):1699-707. et al. 2022 May 19. Bernhard F , Pulse M Generic name: Cefepime [SEF e peem] Disclosure: Audrey O'Connor declares no relevant financial relationships with ineligible companies. Drug class: fourth generation cephalosporins. Of the 10 NDM-5-producing isolates with cefepime/taniborbactam MICs of 8mg/L, 7 did not have the same mutation in PBP3. Cefepime may decrease the excretion rate of Acetaminophen which could result in a higher serum level. Treasure Island (FL): StatPearls Publishing; 2023 Jan. Would you like email updates of new search results? Cefepime/tazobactam is currently being developed at a dose of 2g/2g (q8h 90min infusion) with the purpose of overcoming both ESBL- and AmpC-related resistance and being a carbapenem-sparing regimen.83 Tazobactam alone does not exhibit -lactam activity and does not protect the companion -lactam antibiotic against carbapenemases. Cefepime/taniborbactam MIC50/90 was 8/16mg/L against a global collection of cefepime- (n=85) and meropenem- (n=143) non-susceptible P. aeruginosa isolates (breakpoints for non-susceptibility >8 and >2mg/L, respectively).59 Cefepime/taniborbactam inhibited 71% of cefepime-non-susceptible and 85% of meropenem-non-susceptible isolates at 8mg/L.59 Cefepime/taniborbactam MIC50/90 was 4/8mg/L against another collection of P. aeruginosa isolates (n=14; 200518; country of origin not specified, may be global) with various resistance mechanisms, i.e. , Boice-Sowek J et al. https://clinicaltrials.gov/ct2/show/NCT03554304. 1, 4 Cefepime is normally used to treat severe nosocomial pneumonia and infections caused by multi-resistant microorganisms such as Pseudomonas aeruginosa, and is also indicated for the empirical tr. Bhagwat SS Alternative to Doxycycline: Azithromycin 1 g PO, stat, repeated in 1 week. In another neutropenic murine thigh infection model, where animals were inoculated with four E. coli, three K. pneumoniae and two P. aeruginosa with various resistance mechanisms (VIM, KPC, TEM, SHV-1, OXA-1, CTX-M, AmpC, reduced OmpK35 expression), time above free threshold concentration (%fT>CT, when CT=1mg/L) best described taniborbactam efficacy, with Enterobacterales strains requiring lower taniborbactam exposures (<57.6% fT>CT for 1log kill, when CT=0.063mg/L) than P. aeruginosa (74% fT>CT for 1log kill, when CT=1mg/L).64. Distribution Adults: Average plasma concentrations of cefepime observed in the male adult, after a single IV infusion (30 minutes) or after the IM injection of doses of 500 mg, 1 g and 2 g are summarized in table 1; in table 2 are presented the average concentrations in the tissues and biological fluids. et al. , Aboklaish AF This medication is available in an injectable form to be given directly into a vein (IV) or muscle (IM) by a healthcare professional. Last updated on Apr 7, 2023. ClinicalTrials.gov. Cefepime/zidebactam is generally active against MBL-producing Enterobacterales and Pseudomonas aeruginosa, in vitro and in animal studies, and cefepime/taniborbactam has activity against KPC and OXA-48 producers. Efficacy of cefepime- VNRX-5133, a novel -lactamase inhibitor, against cephalosporin-resistant, ESBL-producing K. pneumoniae in a murine lung infection model. Determining a clinical framework for use of cefepime and -lactam/-lactamase inhibitors in the treatment of infections caused by extended-spectrum--lactamase-producing Enterobacteriaceae. Cefepime is completely absorbed after IM administration. Cefepime/taniborbactam has good in vitro activity against ESBL-, KPC- and OXA-48-producing Enterobacterales. strains with zidebactam MIC32mg/L and included three ESBL producers (CTX-M-9, CTX-M-25, unidentified), two OXA-48 and ESBL coproducers, one KPC and SHV coproducer, one NDM producer and one VIM producer, all of which also had elevated cefepime MICs (2 to >256mg/L). 2016 Jun;60(6):3854-5. Cefepime for Injection is indicated in the treatment of pneumonia (moderate to severe) caused by susceptible strains of Streptococcus pneumoniae, including cases associated with concurrent bacteremia, Pseudomonas aeruginosa, Klebsiella pneumoniae, or Enterobacter species. Uses. This medicine may interact with other drugs or health problems. , Abdelraouf K Cefepime may decrease the excretion rate of Aclidinium which could result in a higher serum level. Less than 1% of the administered dose is recovered from urine as N-methylpyrrolidine (NMP), 6.8% as NMP-N-oxide, and 2.5% as an epimer.5,6 Dosage adjustments are required in patients with renal dysfunction or those undergoing hemodialysis, due to the importance of renal excretion in eliminating cefepime.5,6, Healthy adult male volunteers (n=9) given cefepime had an average half-life of 2 hours. Cefepime, a wide-spectrum -lactam antibiotic, has been in use for the treatment of serious bacterial infections for almost 25years. This activity will highlight the mechanism of action, adverse effects, and other essential factors such as dosing and monitoring appropriate for all interprofessional team members when treating patients with cefepime. government site. Chapman TM, Perry CM. Selection of EUCAST disk potency for WCK 5222 (cefepime-zidebactam, FEP-ZID) susceptibility testing against Enterobacterales, Pseudomonas aeruginosa and Acinetobacter baumannii. , Tabor-Rennie J Safety and Efficacy Study of Cefepime-AAI101 in the Treatment of Complicated Urinary Tract Infections. Cefepime/zidebactam MIC50/90 was 8/32mg/L against 19 P. aeruginosa isolates (collected at CDC, FDA and Louisville Hospital in the USA, time period unspecified) exhibiting multiple resistance mechanisms (i.e. 2022 Sep 19. , Mettus R Bethesda, MD 20894, Web Policies and 5 Proteeae), 15 OXA-48-like enzyme producers (5 E. coli and 10 Klebsiella spp. , Antimicrobial activity of cefepime in combination with VNRX-5133 against a global 2018 surveillance collection of clinical isolates. Safety announcement; Additional Information for Patients and Caregivers; Additional Information for Health Care Professionals; Data Summary for cefepime. WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. (n=179) were 0.12/0.5 (16/>64), 0.5/>64 (64/>64), 0.5/4 (1/16) and 0.12/0.25 (1/>64) mg/L, respectively. , Patel M Median (IQR) time until recovery from the discontinuation of cefepime was 3.0 (2.0-5.0) days. Cefepime/enmetazobactam activity was evaluated against a panel of MDR E. coli and K. pneumoniae isolates (n=223) collected during 201314 from hospitals across the USA.72 Cefepime/enmetazobactam, cefepime and meropenem MIC50/90s were 0.125/64mg/L (range 0.06 to >64mg/L, % susceptible not reported), >64/>64mg/L (range 4 to >64, 0% susceptible, breakpoint 2mg/L) and 0.125/64mg/L (range 0.06 to >64mg/L, 70% susceptible, breakpoint 1mg/L), respectively.72 Cefepime/enmetazobactam MIC50/90 was 0.125/0.5mg/L (range 0.06 to >64mg/L) against ESBL-producing isolates (n=150, 42% bloodstream isolates, ESBL types not specified).72 In this study, cefepime/enmetazobactam MIC50/90 against cefepime- and piperacillin/tazobactam-resistant isolates (n=208 and 127, respectively) and against carbapenemase producers (n=50) were 0.125/64, 1/>64 and 32/>256mg/L, respectively, (MIC range 0.06 to >64mg/L for all groups).72, When tested against a global Enterobacterales collection (US and European hospitals, 201415), cefepime/enmetazobactam MIC50/90 was 0.06/0.12mg/L (range 0.01632mg/L, % susceptible not provided) against mainly ESBL-producing E. coli (n=109; 98 CTX-M, 4 SHV, 2 TEM and 7 AmpC) and was 0.12/1mg/L (range 0.038mg/L, % susceptible not provided) against mainly ESBL-producing K. pneumoniae (n=102; 79 CTX-M, 10 SHV, 1 AmpC), respectively.70 Cefepime and meropenem MIC50/90s were 16/>64 and 0.03/0.03mg/L, respectively, for ESBL-producing E. coli, and were 64/>64 and 0.03/1mg/L, respectively, for ESBL-producing K. pneumoniae.70 Cefepime/enmetazobactam, cefepime and meropenem MIC50/90s were 0.06/0.25 (range 0.0152), 0.06/05 and 0.03/0.12mg/L, respectively, for E. aerogenes and were 0.12/1 (range 0.03 to >64) , 0.12/16 and 0.03/12mg/L, respectively, for E. cloacae (100 isolates of each species, -lactamases not specified).70, Enmetazobactam does not enhance cefepime activity against contemporary P. aeruginosa isolates. et al. amoxicillin, doxycycline, ciprofloxacin, azithromycin, metronidazole, cephalexin, clindamycin, ceftriaxone, levofloxacin, Augmentin. et al. Kassel LE However, many people have no side effects or only have minor side effects. Cefepime/tazobactam, given over 90min, will be compared with meropenem for the treatment of cUTI and acute pyelonephritis in a Phase III non-inferiority trial (clinicaltrials.gov identifier NCT03630081).90 This trial is planned to commence in January/February 2021 (Wockhardt, personal communication). ClinicalTrials.gov. Cefepime cephalosporin salts (U.S. Patent No. Cefepime/tazobactam is especially attractive, combining an AmpC-stable cephalosporin with a clinically established inhibitor, active against ESBLs and suitable for high-dose administration. Evaluation of studies on extended versus standard infusion of beta-lactam antibiotics. The cefepime/enmetazobactam combination is active in vitro against ESBL- and AmpC-producing Enterobacterales and P. aeruginosa except the MDR P. aeruginosa strains (Table3).70 Cefepime/enmetazobactam 2g/0.5g q8h (2h infusion) is currently under clinical development. Cefepime/AAI101 Phase 2 Study in Hospitalized Adults With cUTI. There is an ongoing need for effective carbapenem-sparing regimens against ESBL and AmpC producers91,92 and highly potent antibiotics active against the broad range of carbapenemases now observed around the world. Against a collection of 21 P. aeruginosa isolates (SENTRY Antimicrobial Surveillance Program, time period unspecified) with AmpC overexpression and 12 isolates with MBL production, cefepime/zidebactam (1:1) MIC50/90 was 4/8mg/L for both groups (cefepime and zidebactam MIC50/90s were 16/64 and 8/32mg/L, respectively, for AmpC producers and 32/128 and 4/16mg/L, respectively, for MBL producers).37, Cefepime/zidebactam MIC50/90 was 8/16mg/L for 126 carbapenem-resistant P. aeruginosa clinical isolates collected at New York City medical centres (201314).40 MIC50/90 values were 16/>16mg/L, both for cefepime and zidebactam. In vitro activities of cefepime/BLI combinations against contemporary clinical isolates. In: StatPearls [Internet]. Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. Written by Cerner M , Castanheira M and transmitted securely. et al. Cefepime injection is used to treat bacterial infections in many different parts of the body. , Nordmann P Indication : Pneumonia (moderate to severe) 2.1.7 Cefepime/Zidebactam. Cefepimes high potency, AmpC stability and a chemical structure easier to protect from -lactamases gives it natural advantages over other cephalosporins or penicillins. Simulation studies show that 2g q12h for MIC=4mg/L and 2g q8h for MIC=8mg/L dosing do not reach target attainment. Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances. Some drugs may have another patient information leaflet. In: StatPearls [Internet]. Imipenem MICs were also low (4mg/L) for 5 of these 10 isolates.39 One isolate had an MIC of 32mg/L, both for cefepime/zidebactam and imipenem, and was a coproducer of a VIM-like carbapenemase, SHV-12 and an SHV-1-like -lactamase.39, Against another collection of 93 KPC-producing carbapenem-resistant K. pneumoniae clinical isolates collected at New York City medical centres (201314), cefepime/zidebactam MIC50/90 was 0.25/2mg/L (cefepime and zidebactam MIC50/90s of >16/>16 and 0.5/>16mg/L, respectively).40, Cefepime/zidebactam was active against 15 selected isolates (Antimicrobial Resistance Isolate Bank, Atlanta, GA, USA; Jackson Memorial Hospital, Miami, FL, USA) coproducing MBLs (13 NDM, 1 VIM-1 and 1 IMP-4) and serine -lactamases, including various ESBLs, OXA-48 and OXA-232 (6 NDM and OXA-48-like coproducers), at an MIC of 2mg/L (cefepime and carbapenem susceptibilities unspecified; all isolates resistant to meropenem/vaborbactam).41, Zidebactam alone displays antipseudomonal activity driven by PBP2 inhibition that leads to fragile cell (spheroplast) formation, outer membrane disruption and subsequent protection from common membrane-bound resistance mechanisms exhibited by P. aeruginosa.31 When combined with the PBP3 inhibitor cefepime, bacterial killing is enhanced, leading to a potent bactericidal effect.31, Zidebactam at 8mg/L inhibited 33/50 P. aeruginosa isolates (10 AmpC derepressed mutants, 10 MBL producers, 10 with up-regulated efflux pump, 10 cystic fibrosis isolates with mixed resistance mechanisms and 10 -lactam-susceptible controls) from the PHE diagnostic laboratories in the UK (time period unspecified).29 Cefepime/zidebactam at 8+8mg/L inhibited 9/10 isolates with derepressed AmpC (cefepime MIC=4128mg/L, meropenem MIC=0.55mg/L), 8/10 with MBLs (cefepime MIC16mg/L, meropenem MIC32mg/L), 8/10 with up-regulated efflux (cefepime MIC8mg/L, meropenem MIC16mg/L) and 9/10 cystic fibrosis isolates (cefepime MIC32mg/L, meropenem MIC8mg/L).29. 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