Cefepime: A Fourth-Generation Parenteral Cephalosporin

1996 ◽  
Vol 30 (12) ◽  
pp. 1414-1424 ◽  
Author(s):  
Michael A Wynd ◽  
Joseph A Paladino
Keyword(s):  
Clinical Trials ◽  
Clinical Efficacy ◽  
Fourth Generation ◽  
Third Generation ◽  
Gram Positive ◽  
Gram Negative ◽  
Beta Lactamases ◽  
Tract Infections ◽  
Third Generation Cephalosporins

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. CONCLUSIONS: Cefepime may have several chemical and pharmacologic advantages over currently available third-generation cephalosporins. In vitro data indicate that cefepime retains activity against some, but not all, gram-negative bacteria resistant to third-generation cephalosporins; however, clinical efficacy against infections due to resistant pathogens remains to be established. Cefepime was at least as effective as comparators during clinical trials, and may prove to be a viable alternative to other currently available agents.

In Vitro Activity of Gepotidacin Against Gram-negative and Gram-positive Anaerobes

2021 ◽  
Author(s):  
Meredith A. Hackel ◽  
James A. Karlowsky ◽  
Michele A. Canino ◽  
Daniel F. Sahm ◽  
Nicole E. Scangarella-Oman
Keyword(s):  
Clinical Trials ◽  
Vitro Activity ◽  
Phase Iii ◽  
In Vitro Activity ◽  
Gram Positive ◽  
Gram Negative ◽  
Phase Iii Clinical Trials ◽  
Agar Dilution

Gepotidacin (formerly GSK2140944) is a first in class triazaacenaphthylene antibacterial currently in Phase III clinical trials. When tested against Gram-negative ( n =333) and Gram-positive ( n =225) anaerobes by agar dilution, gepotidacin inhibited 90% of isolates (MIC 90 ) at concentrations of 4 and 2 μg/ml, respectively. Given gepotidacin’s in vitro activity against the anaerobic isolates tested, further study is warranted to better understand gepotidacin’s utility in the treatment of infections caused by clinically relevant anaerobic organisms.

Cefiderocol: A new cephalosporin stratagem against multidrug resistant gram-negative bacteria

2021 ◽  
Author(s):  
Sharon Ong’uti ◽  
Mary Czech ◽  
Elizabeth Robilotti ◽  
Marisa Holubar
Keyword(s):  
Clinical Trials ◽  
Multidrug Resistant ◽  
Cell Entry ◽  
Phase Iii ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Phase Iii Clinical Trials ◽  
Carbapenem Resistant ◽  
Tract Infections

Abstract Cefiderocol is a novel injectable siderophore cephalosporin which hijacks the bacterial iron transport machinery to facilitate cell entry and achieve high periplasmic concentrations. It has broad in vitro activity against gram-negative bacteria, including multidrug resistant (MDR) organisms like carbapenem resistant Enterobacterales (CRE), carbapenem resistant Pseudomonas aeruginosa and Acinetobacter baumannii. It was approved by the Food and Drug Administration (FDA) for the treatment of complicated urinary tract infections and nosocomial pneumonia based on clinical trials demonstrating noninferiority to comparators. In this review, we summarize the available in vitro and clinical data, including recent evidence from 2 phase III clinical trials (APEKS-NP and CREDIBLE-CR), and discuss the place of cefiderocol in the clinician’s armamentarium against MDR gram-negative infections.

Carriage of Staphylococcus aureus and of Gram-Negative Bacilli Resistant to Third-Generation Cephalosporins in Cirrhotic Patients A Prospective Assessment of Hospital-Acquired Infections

2001 ◽  
Vol 22 (7) ◽  
pp. 427-432 ◽  
Author(s):  
Catherine Dupeyron ◽  
Bernard Campillo ◽  
Nicole Mangeney ◽  
Muriel Bordes ◽  
Jean-Philippe Richardet ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Urinary Tract ◽  
Urinary Tract Infections ◽  
Third Generation ◽  
Gram Negative ◽  
Bacterial Peritonitis ◽  
Prospective Assessment ◽  
Cirrhotic Patients ◽  
Tract Infections ◽  
Third Generation Cephalosporins

AbstractObjective:To study the relation between Staphylococcus aureus nasal and stool colonization, stool carriage of gram-negative bacilli resistant to third-generation cephalosporins (CephR), and subsequent infections during hospitalization.Design:Prospective study.Patients:551 cirrhotic patients with 589 consecutive hospital stays. All patients were screened within 48 hours of admission; 589 nasal swabs, 417 stool specimens, and 589 urine samples were analyzed.Results:Carriage rates were 18.8% for methicillin-sensitive S aureus (MSSA), 16.3% for methicillin-resistant S aureus (MRSA), and 13.7% for CephR. We observed 87 episodes of spontaneous bacterial peritonitis, 63 cases of bacteremia, and 167 urinary tract infections occurred. Only 1 case of bacteremia and 4 urinary tract infections due to CephR occurred in patients carrying the same organism in their stools. The risk of MRSA ascitic fluid infections, bacteremia, and urinary tract infections was 3.1% versus 1% (not significant), 8.3% versus 0.8% (P<.001), and 11.4% versus 0.6% (P<.001) in carriers and noncarriers, respectively. Pulsed-field gel electrophoresis (PFGE) of isolates from 16 patients infected by MSSA (3 cases) and MRSA (13 cases) demonstrated that the colonizing strains matched the invasive strains in the 3 MSSA cases and in 8 of 13 MRSA cases.Conclusion:Carriage of CephR strains is not associated with subsequent infection by these organisms in hospitalized cirrhotic patients. In contrast, MRSA carriage was an important risk factor for MRSA bacteremia and urinary tract infection.

The Cephalosporin Antibiotic Agents— III. Third-Generation Cephalosporins

1985 ◽  
Vol 6 (2) ◽  
pp. 78-83 ◽  
Author(s):  
T. Donald Marsh
Keyword(s):  
Generation Cephalosporin ◽  
Third Generation ◽  
Negative Spectrum ◽  
Gram Negative ◽  
Beta Lactamases ◽  
Large Numbers ◽  
Gram Negative Organisms ◽  
Dosing Intervals ◽  
First And Second Generation

The third-“generation” cephalosporin antibiotics (Table 1) represent a class of agents with an expanded gram-negative spectrum of activity beyond that of the first- and second-“generation” cephalosporins. Greater stability to beta-lactamases produced by gram-negative organisms confers to these agents a greater bactericidal action against the Enterobacteriaceae. Large bacterial inocula (105/ml) in vitro significantly increase the minimum inhibitory and bactericidal concentrations (MIC and MBC) explaining treatment failures with these agents in infections associated with large numbers of organisms. The pharmacokinetic features of some of the agents allow prolongation of dosing intervals, and enhanced tissue penetration amplifies their clinical utility in infections distant from the bloodstream (eg, meningitis).

scholarly journals Quinolone resistance in different uropathogens isolated from urine cultures in patients with urinary tract infection

2020 ◽  
Author(s):  
Jorge Angel Almeida Villegas ◽  
Iris Mellolzy Estrada Carrillo ◽  
Rodolfo Garcia Contreras ◽  
Silvia Patricia Peña
Keyword(s):  
Urinary Tract Infection ◽  
Urinary Tract ◽  
Tract Infection ◽  
Urinary Tract Infections ◽  
Gram Positive ◽  
Gram Negative ◽  
Beta Lactamases ◽  
Extended Spectrum ◽  
Extended Spectrum Beta Lactamases ◽  
Tract Infections

AbstractObjectiveTo identify patterns of resistance against quinolones in various uropathogens in urinary tract infections in the population of the Toluca valley, MexicoIntroductionQuinolones are antibiotics with a spectrum of activity for both gram-positives and gram-negatives and are antibiotics used for the empirical treatment of urinary tract infections. Recently, a high index of resistance to quinolones has been reported due to different mechanisms on the part of bacteria, however the one that has taken the greatest importance is the presence of extended spectrum beta-lactamasesMethods155 samples were collected from patients with suspected urinary tract infection without exclusion criteria such as age or gender. Automated equipment was used for the identification of the etiological agent and sensitivity tests to quinolones.ResultsThe results positives were divided to evaluate which of the two antibiotics studied had greater resistance. For ciprofloxacin there are 27 resistant strains 37%, 1 strain with intermediate resistance 1% and 45 susceptible strains 62%. For levofloxacin 26 strains are resistant 36%, 41 strains are sensitive 56% and 6 strains show intermediate sensitivity 8%.ConclusionDifferent microorganisms, both gram-positive and gram-negative, were isolated and it can be observed that gram-negative strains are the ones with the greatest resistance against quinolones, mainly Escherichia coli, which produces extended-spectrum beta-lactamases, in the case of gram-positive resistance patterns are variable with a tendency towards sensitivity.

scholarly journals An Update on Eight “New” Antibiotics against Multidrug-Resistant Gram-Negative Bacteria

2021 ◽  
Vol 10 (5) ◽  
pp. 1068
Author(s):  
Erlangga Yusuf ◽  
Hannelore I. Bax ◽  
Nelianne J. Verkaik ◽  
Mireille van Westreenen
Keyword(s):  
Drug Administration ◽  
Food And Drug Administration ◽  
Treatment Options ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Beta Lactamases ◽  
New Antibiotics ◽  
Tract Infections ◽  
The U.S

Infections in the ICU are often caused by Gram-negative bacteria. When these microorganisms are resistant to third-generation cephalosporines (due to extended-spectrum (ESBL) or AmpC beta-lactamases) or to carbapenems (for example carbapenem producing Enterobacteriales (CPE)), the treatment options become limited. In the last six years, fortunately, there have been new antibiotics approved by the U.S. Food and Drug Administration (FDA) with predominant activities against Gram-negative bacteria. We aimed to review these antibiotics: plazomicin, eravacycline, temocillin, cefiderocol, ceftazidime/avibactam, ceftolozane/tazobactam, meropenem/vaborbactam, and imipenem/relebactam. Temocillin is an antibiotic that was only approved in Belgium and the UK several decades ago. We reviewed the in vitro activities of these new antibiotics, especially against ESBL and CPE microorganisms, potential side effects, and clinical studies in complicated urinary tract infections (cUTI), intra-abdominal infections (cIAI), and hospital-acquired pneumonia/ventilator-associatedpneumonia (HAP/VAP). All of these new antibiotics are active against ESBL, and almost all of them are active against CPE caused by KPC beta-lactamase, but only some of them are active against CPE due to MBL or OXA beta-lactamases. At present, all of these new antibiotics are approved by the U.S. Food and Drug Administration for cUTI (except eravacycline) and most of them for cIAI (eravacycline, ceftazidime/avibactam, ceftolozane/tazobactam, and imipenem/relebactam) and for HAP or VAP (cefiderocol, ceftazidime/avibactam, ceftolozane/tazobactam, and imipenem/relebactam).

Review of in Vitro Activity, Pharmacokinetic Characteristics, Safety, and Clinical Efficacy of Cefprozil, a New Oral Cephalosporin

1993 ◽  
Vol 27 (9) ◽  
pp. 1082-1089 ◽  
Author(s):  
Steven L. Barriere
Keyword(s):  
Clinical Trials ◽  
Adverse Effects ◽  
Clinical Efficacy ◽  
Broad Spectrum ◽  
Safety Data ◽  
Beta Lactamase ◽  
Beta Lactam ◽  
Oral Cephalosporin ◽  
Gram Negative

OBJECTIVE: To review the pharmacokinetics, microbiology, clinical efficacy, safety, and tolerance of cefprozil, a new, broad-spectrum oral cephalosporin. DATA SOURCES: Published clinical trials and microbiologic, pharmacokinetic, and safety data were identified by MEDLINE; additional references were derived from bibliographies of these articles; microbiologic data on file were provided by Bristol-Myers Squibb. STUDY SELECTION: Only published comparative clinical trial reports are included in the review of clinical efficacy. Noncomparative clinical data pertaining to uses of cefprozil not approved by the Food and Drug Administration are not included. DATA SYNTHESIS: Data are presented on the in vitro microbiologic activity of cefprozil against 10 152 bacterial isolates, including most of the clinically important streptococci (e.g., Streptococcus pyogenes, Streptococcus pneumoniae), beta-lactamase-positive and -negative Staphylococcus aureus and Haemophilus influenzae, Moraxella catarrhalis, Escherichia coli, Proteus mirabilis, Clostridium difficile, and numerous other gram-negative aerobes and anaerobes. In clinical trials, cefprozil appears to be at least as effective as commonly used comparison agents such as cefaclor, cefixime, and amoxicillin/clavulanic acid. Additionally, cefprozil is better tolerated than the latter two agents, especially with regard to gastrointestinal adverse effects. CONCLUSIONS: Cefprozil is a broad-spectrum cephalosporin that provides coverage against both gram-negative and -positive bacteria that may cause otitis media, pharyngitis/tonsillitis, skin and skin-structure infections, secondary bacterial infection of acute bronchitis, and acute bacterial exacerbations of chronic bronchitis. The beta-lactamase stability of cefprozil appears to exceed that of other oral cephalosporins for some important pathogens. Cefprozil is used primarily for second-line treatment as less-expensive, first-line generic alternatives generally are available. Cefprozil demonstrates clinical advantages over many other orally administered beta-lactam antibiotics in terms of antimicrobial spectrum, a once- or twice-daily dosing regimen, and/or reduced incidence of adverse effects.

scholarly journals Ability of Microorganisms, Causing Respiratory Infections in Children, to Form Biofilms in vitro

2021 ◽  
Vol 6 (1) ◽  
pp. 177-183
Author(s):  
H. O. Isaieva ◽  
◽  
M. M. Mishyna ◽  
Y. A. Mozgova ◽  
M. O. Gonchar ◽  
...  
Keyword(s):  
Intensive Care Unit ◽  
Respiratory Tract ◽  
Optical Density ◽  
Respiratory Diseases ◽  
Respiratory Tract Infections ◽  
Respiratory Infections ◽  
Gram Positive ◽  
Gram Negative ◽  
Tract Infections

The purpose of the study was to detect ability to form biofilms by microorganisms that cause respiratory tract infections. Materials and methods. The study involved 97 strains of microorganisms. Microorganisms were isolated from children with respiratory tract infections. All strains, isolated from patients, were able to form biofilms. There were 44 strains of S. aureus (from patients with pneumonia – 13 strains, from patients with other respiratory diseases – 31), 34 strains of S. pneumoniae (pneumonia – 27 strains, other respiratory diseases – 7), 13 strains of K. pneumoniae (pneumonia – 6 strains, other respiratory diseases – 7), 6 strains of P. aeruginosa (pneumonia – 5 strains, other respiratory diseases – 1). Children were treated at the pulmonary department and intensive care unit in Kharkiv Regional Children's Clinical Hospital. Results and discussion. The optical density of primary biofilms formed by Gram-positive microorganisms was 1.33±0.24 Units of OD, and their secondary biofilms was 0.32±0.10 Units of OD. In patients with pneumonia optical density of primary biofilms of Gram-positive microorganisms was 1.48±0.21 Units of OD and of secondary biofilms was 0.30±0.08 Units of OD. Optical density of primary biofilms of Gram-positive microorganisms in patients with other respiratory infections was 1.18±0.15 Units of OD, of secondary biofilms was 0.35±0.12 Units of OD. The optical density of primary biofilms formed by Gram-negative microorganisms was 2.01±1.03 Units of OD, optical density of secondary biofilms was 1.06±0.42 Units of OD. In patients with pneumonia optical density of primary biofilms of Gram-negative microorganisms was 2.57±0.87 Units of OD, of secondary biofilms was 1.21±0.50 Units of OD. Optical density of primary biofilms of Gram-negative microorganisms in patients with other respiratory infections was 1.24±0.66 Units of OD, of secondary biofilms was 0.84±0.11 Units of OD. Conclusion. Gram-negative microorganisms in general formed more massive biofilms compared with Gram-positive microorganisms. Among all microorganisms P. aeruginosa formed the thickest primary and secondary biofilms. Strains of P. aeruginosa isolated from patients with pneumonia formed the thickest primary and secondary biofilms. Strains of S. aureus isolated from patients with other respiratory infections formed most massive primary biofilms, strains of K. pneumoniae formed the hardest secondary biofilms in this group

scholarly journals Comparative Activity of Cefepime with Several Antimicrobials against Aerobic Gram-Negative and Gram-Positive Organisms Isolated from Patients across Canada in 1993

1995 ◽  
Vol 6 (5) ◽  
pp. 258-262 ◽  
Author(s):  
Donald E Low ◽  
Keyword(s):  
Tertiary Care ◽  
Empirical Therapy ◽  
Generation Cephalosporin ◽  
Fourth Generation ◽  
Care Hospital ◽  
Gram Positive ◽  
In Vitro Susceptibility ◽  
Gram Negative ◽  
Minimal Inhibitory Concentrations

To compare the activity of cefepime, a fourth-generation cephalosporin, with several available antimicrobials, in vitro susceptibility studies were carried out on bacteria commonly associated with various infections, including sepsis. Ten tertiary care hospital laboratories in six provinces provided 1276 clinically relevant isolates of aerobic Gram-negative bacilli and Gram-positive cocci during 1993. When the activity of each of the antimicrobials was determined against all isolates submitted, cefepime, piperacillin/tazobactam, imipenem and ciprofloxacin all had minimal inhibitory concentrations for 90% of the organisms (mic90) two or more dilutions below themicresistant category. Gentamicin’smic90against all organisms tested was one dilution below themicresistant category. Themic90s of the third-generation cephalosporins, piperacillin and ticarcillin/clavulanate, forEnterobacterspecies fell in the resistant category. This is presumably due to constitutive high level chromosomal cephalosporinase production. Themic90s of cefepime forEnterobacterspecies was three or more dilutions below themicresistant category. Themic90s of all antimcrobials againstStaphylococcus aureus, with the exception of ceftazidime and piperacillin, hadmic90categories two or more dilutions below the resistant category. The activity of cefepime, piperacillin/tazobactam, imipenem, ciprofloxacin and gentamicin make them excellent candidates for the empirical therapy of serious infections due to aerobic Gram-negative bacilli andS aureus.

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