cefepime and Acute-Disease

Cefepime/enmetazobactam is a novel β-lactam/β-lactamase inhibitor combination and a potential empirical therapy for resistant gram-negative infections.. To evaluate whether cefepime/enmetazobactam was noninferior to piperacillin/tazobactam for the primary outcome of treatment efficacy in patients with complicated urinary tract infections (UTIs) or acute pyelonephritis.. A phase 3, randomized, double-blind, active-controlled, multicenter, noninferiority clinical trial conducted at 90 sites in Europe, North and Central America, South America, and South Africa. Recruitment occurred between September 24, 2018, and November 2, 2019. Final follow-up occurred November 26, 2019. Participants were adult patients aged 18 years or older with a clinical diagnosis of complicated UTI or acute pyelonephritis caused by gram-negative urinary pathogens.. Eligible patients were randomized to receive either cefepime, 2 g/enmetazobactam, 0.5 g (n = 520), or piperacillin, 4 g/tazobactam, 0.5 g (n = 521), by 2-hour infusion every 8 hours for 7 days (up to 14 days in patients with a positive blood culture at baseline).. The primary outcome was the proportion of patients in the primary analysis set (patients who received any amount of study drug with a baseline gram-negative pathogen not resistant to either treatment and ≥105 colony-forming units [CFU]/mL in urine culture or the same pathogen present in concurrent blood and urine cultures) who achieved overall treatment success (defined as clinical cure combined with microbiological eradication [<103 CFU/mL in urine] of infection). Two-sided 95% CIs were computed using the stratified Newcombe method. The prespecified noninferiority margin was -10%. If noninferiority was established, a superiority comparison was also prespecified.. Among 1041 patients randomized (mean age, 54.7 years; 573 women [55.0%]), 1034 (99.3%) received study drug and 995 (95.6%) completed the trial. Among the primary analysis set, the primary outcome occurred in 79.1% (273/345) of patients receiving cefepime/enmetazobactam compared with 58.9% (196/333) receiving piperacillin/tazobactam (between-group difference, 21.2% [95% CI, 14.3% to 27.9%]). Treatment-emergent adverse events occurred in 50.0% (258/516) of patients treated with cefepime/enmetazobactam and 44.0% (228/518) with piperacillin/tazobactam; most were mild to moderate in severity (89.9% vs 88.6%, respectively). A total of 1.7% (9/516) of participants who received cefepime/enmetazobactam and 0.8% (4/518) of those who received piperacillin/tazobactam did not complete the assigned therapy due to adverse events.. Among patients with complicated UTI or acute pyelonephritis caused by gram-negative pathogens, cefepime/enmetazobactam, compared with piperacillin/tazobactam, met criteria for noninferiority as well as superiority with respect to the primary outcome of clinical cure and microbiological eradication. Further research is needed to determine the potential role for cefepime/enmetazobactam in the treatment of complicated UTI and pyelonephritis.. ClinicalTrials.gov Identifier: NCT03687255.

Topics: Acute Disease; Anti-Bacterial Agents; beta-Lactamase Inhibitors; Cefepime; Double-Blind Method; Drug Combinations; Female; Gram-Negative Bacterial Infections; Humans; Infusions, Intravenous; Male; Middle Aged; Piperacillin, Tazobactam Drug Combination; Pyelonephritis; Urinary Tract Infections

This study aims to evaluate the clinical efficacy and safety of intravenous Cefoselis injection for the treatment of acute moderate and severe bacterial infections.. A multicenter, double-blind, randomized clinical trial was carried out using Cefepime as control. Patients received 1.0 g of either Cefoselis or Cefepime for moderate infections or 2.0 g for severe infections at an interval of 12 hours for 7 to 14 days. A total of 276 patients (138 with Cefoselis, 138 with Cefepime) with respiratory or urinary tract infections were enrolled in the study. Up to 137 and 124 patients receiving Cefoselis and 132 and 125 patients receiving Cefepime were eligible for the ITT (intent to treat) and PP (per protocol) analyses, respectively.. At the end of the treatment, the cure rates and effective rates were 59.68% (74/124) and 93.55% (116/124) with Cefoselis, and 56.00% (74/124) and 90.40% (116/124) with Cefepime. The bacterial eradication rates of the two groups were 90.32% and 93.85%, respectively. No statistical differences were observed on the above-mentioned parameters between the two groups (all p > 0.05). Adverse events, mainly mild aminotransferase elevation and mild leukopenia, were observed in 11.59% (16/138) and 13.77% (19/138) of patients with Cefoselis and Cefepime, respectively (p > 0.05).. Cefoselis is an effective and safe choice against acute moderate and severe respiratory infections and UTI (urinary tract infection).

Topics: Acute Disease; Anti-Bacterial Agents; Bacterial Infections; Cefepime; Ceftizoxime; Cephalosporins; Double-Blind Method; Female; Humans; Male; Respiratory Tract Infections; Urinary Tract Infections

We conducted a prospective, randomized, open-label trial to evaluate the efficacy and tolerability of cefepime in the treatment of osteomyelitis caused by Gram-negative bacilli. Hospitalized patients with diagnosis of osteomyelitis due to Gram-negative bacilli susceptible to cefepime were elegible for enrollment. Cefepime was administered intravenously or intramuscularly (2 g every 8 or 12 hours). Microorganisms were considered susceptible to cefepime when the MIC was <8 mg/l. Forty-five patients with bone infections were enrolled, forty-three with osteomyelitis (22 chronic and 21 acute) and two with arthritis. In the per protocol analysis 42 patients were evaluated: 30 (71.4%) were cured. In the intent to treat analysis 45 patients were evaluated: 33 (73.3%) were cured. Our trial suggests that cefepime is as effective as other modern parenteral beta-lactam antibiotics in the treatment of osteomyelitis due to Gram-negative bacilli.

Topics: Acute Disease; Adult; Aged; Aged, 80 and over; Cefepime; Cephalosporins; Chronic Disease; Female; Gram-Negative Bacterial Infections; Humans; Male; Middle Aged; Osteomyelitis; Patient Selection

A multicentre trial was performed on the activity of cefepime in comparison with ceftazidime, ceftriaxone, piperacillin/tazobactam, imipenem and ciprofloxacin against severe hospital infection pathogens in intensive care units. The isolates of Escherichia coli and Proteus spp. from the majority of the centres were highly susceptible to the antibiotics (90 to 100 per cent of the isolates). In some centres up to 40 per cent of the isolates produced ESBL. The isolates of Klebsiella spp. were characterized by lower susceptibility, in some centres the frequency of the strains producing ESBL exceeded 90 per cent, by the MIC geometric mean cefepime was superior to the third generation cephalosporins, the frequency of resistance to ciprofloxacin ranged from 0 to 31 per cent, no resistance to imipenem was recorded. The frequency of resistance to the third generation cephalosporins and piperacillin/tazobactam in Enterobacter spp., Serratia spp., Citrobacter spp., Morganella spp., and Providencia spp. ranged from 10 to 52 per cent, the resistance to cefepime equaled 0-11 per cent, 0 to 17 per cent of the isolates were resistant to ciprofloxacin, some isolates were resistant to imipenem. As for the nonfermenting microorganisms their resistance to all the antibiotics tested was comparatively high and markedly differed in various centres. As a whole, 7 per cent of all the isolates of the nonfermenting organisms was resistant to cefepime, 10 per cent was resistant to imipenem, 17 per cent was resistant to ceftazidime, 21 per cent was resistant to piperacillin/tazobactam and 36 per cent was resistant to ciprofloxacin.

Topics: Acute Disease; Anti-Bacterial Agents; Cefepime; Cephalosporins; Cross Infection; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Humans; Microbial Sensitivity Tests; Russia

Cephalosporins are one of the mainstays of antibiotic therapy, and third-generation cephalosporins are first-line agents for the treatment of many types of serious infections, including those of nosocomial origin. Gaps in activity of currently available third-generation cephalosporins such as cefotaxime, cefoperazone, ceftriaxone, and ceftazidime, and increasing reports of gram-negative bacilli resistance to some of these agents, especially Klebsiella pneumoniae, Pseudomonas aeruginosa, and Enterobacter spp., make it necessary to investigate new compounds. Cefepime, a fourth-generation cephalosporin with a wide range of activity against gram-positive and gram-negative bacteria, including multi-resistant strains of Enterobacteriaceae, was evaluated in comparison with ceftazidime for the treatment of serious infections in hospitalized patients. Ceftazidime is a commonly prescribed third-generation cephalosporin used for empiric treatment of serious infections such as pneumonia, urinary tract infection, and skin and skin-structure infection. This investigation was an open, randomized comparative study involving 882 patients in North America. Cefepime 2 g every 12 hours demonstrated similar efficacy to that of ceftazidime 2 g every 8 hours for the treatment of pneumonia and urinary tract infection (including cases associated with concurrent bacteremia), and skin and skin-structure infections. The bacteriologic responses were generally >85%. The most common pathogens isolated were Escherichia coll, Streptococcus pneumoniae, P. aeruginosa, K. pneumoniae, Haemophilus influenzae, Staphylococcus aureus, and Streptococcus, group B. Overall, approximately 94% of pathogens isolated in pretreatment cultures were susceptible to cefepime and ceftazidime. Cefepime and ceftazidime were well tolerated; only 3% of patients in each group discontinued therapy because of an adverse event. The most common adverse events were headache, diarrhea, nausea, vomiting, pruritus, and rash. The results of this study indicate that cefepime is a promising, effective, and safe single-agent therapy for serious infections in hospitalized patients.

Topics: Acute Disease; Analysis of Variance; Bacterial Infections; Cefepime; Ceftazidime; Cephalosporins; Cross Infection; Female; Humans; Infusions, Intravenous; Male; Middle Aged; United States

Patients with bacterial pneumonia often are treated empirically with parenteral broad-spectrum antimicrobials intended to cover potential gram-negative and gram-positive pathogens. However, beta-lactamase-mediated resistance has developed to many of these antimicrobials, particularly third-generation cephalosporins, and has led to the development of fourth-generation agents that are relatively beta-lactamase stable. The purpose of these studies was to compare the efficacy and safety of the fourth-generation agent, cefepime, with that of the third-generation agent, ceftazidime, in the treatment of hospitalized patients with moderate-to-severe bacterial pneumonia. A total of 336 (97 evaluable) patients were enrolled in an open-label study, and 99 (23 evaluable) patients were enrolled in a blinded study of patients with lower respiratory tract infections (LRTI) including pneumonia. Patients were randomized to receive either cefepime 1 g every 12 hours or ceftazidime 1 g every 8 hours given as an intravenous infusion over 30 minutes. Efficacy analysis included the evaluable patients while the safety analysis included all patients. The results in the open-label study were as follows: In patients with pneumonia, clinical response was satisfactory in 58 (85%) of 68 patients in the cefepime group and 21 (72%) of 29 patients in the ceftazidime group. Bacteriologic eradication occurred for 75 (93%) of 81 pathogens and 30 (94%) of 32 pathogens isolated from the 68 cefepime-treated patients and 29 ceftazidime-treated patients, respectively. The results in the blinded study were as follows: In patients with pneumonia, clinical response was satisfactory in 12 (80%) of 15 cefepime patients and in 7 (88%) of 8 ceftazidime patients, and the bacteriologic eradication rates were 85% (17/20 pathogens) and 73% (8/11 pathogens) isolated from the 15 cefepime-treated patients and the eight ceftazidime-treated patients, respectively. Among the most frequent adverse events in both groups were nausea, diarrhea, vomiting, and abdominal pain. Similar adverse events were noted in the 99 patients in the blinded study. These studies indicate that the efficacy and safety of cefepime administered at 1 g twice daily is comparable to that of ceftazidime administered at 1 g three times daily for treatment of hospitalized patients with pneumonia caused by susceptible pathogens.

Topics: Acute Disease; Aged; Canada; Cefepime; Ceftazidime; Cephalosporins; Double-Blind Method; Female; Humans; Male; Middle Aged; Pneumonia, Bacterial; Puerto Rico; United States

In patients with acute cholecystitis, antibiotics are used as an adjunct to cholecystectomy to reduce the incidence of postoperative septic complications thought to be related to bactibilia. Combinations of penicillins, or cephalosporins or aminoglycosides, or both, are often used. Cefepime is a fourth-generation cephalosporin with excellent activity against gram-positive and gram-negative bacteria, including Pseudomonas species. It has a prolonged serum half-life, allowing twice-daily dosing, and is not nephrotoxic. This study was undertaken to determine whether or not cefepime was as effective as the combination of gentamicin and mezlocillin in patients with acute cholecystitis. One hundred and forty-nine patients were randomized, two to one, to receive cefepime or gentamicin and mezlocillin. Cefepime was given intravenously at 2 grams every 12 hours; gentamicin, 1.0 to 1.5 milligrams per kilograms every eight hours, and mezlocillin, 3 to 4 grams every four to six hours. All patients underwent cholecystectomy. Bile cultures were obtained, and concentrations of cefepime in blood, bile, peritoneal fluid and gallbladder were determined in a subset of patients. There were 56 evaluable cefepime-treated and 34 evaluable gentamicin and mezlocillin-treated patients. Bactibilia was present in 17 of 56 cefepime-treated patients (30.4 percent) and ten of 34 gentamicin and mezlocillin-treated patients (29.4 percent). Enterococci were recovered in six cefepime-treated patients. Clinical and bacteriologic responses were similar for the cefepime-treated and gentamicin and mezlocillin-treated groups, with one failure in each group, a wound infection in a patient receiving cefepime and a subhepatic abscess in a patients receiving gentamicin and mezlocillin. Other measures of outcome, such as the number of days of fever, days nothing by mouth, days of hospitalization and days of antibiotic therapy were similar in both groups. Cefepime, with every 12 hour dosing, achieved extremely high concentrations in all tissues assayed at the time of the operation, a mean of eight hours after administration. Adverse clinical events were similar in both treatment groups. Cefepime is as effective as gentamicin and mezlocillin in preventing septic complications after cholecystectomy for acute cholecystitis. Cefepime requires fewer doses, does not require drug monitoring, is not associated with nephrotoxicity and may therefore prove to be a cost-effective alternative to combination thera

Topics: Acute Disease; Adult; Aged; Cefepime; Cephalosporins; Chemotherapy, Adjuvant; Cholecystitis; Drug Therapy, Combination; Female; Gentamicins; Humans; Male; Mezlocillin; Middle Aged; Treatment Outcome

Topics: Acute Disease; Adult; Cefepime; Cephalosporins; Cholecystectomy; Cholecystitis; Female; Humans; Infusions, Intravenous; Male; Middle Aged; Surgical Wound Infection

Cefepime is a new broad-spectrum cephalosporin with activity against Staphylococcus, Streptococcus, Pseudomonas, and the Enterobacteriaceae. The purpose of this study was to measure cefepime concentrations in plasma, peritoneal fluid, bile fluid and appendix tissue in patients undergoing elective cholecystectomy. Patients were randomly assigned to receive either cefepime, 2 g intravenously in phosphate buffer (IVPB) q 12 h or gentamicin 1.5 mg/kg IVPB q 8 h plus mezlocillin 4 g IVPB q 6 h. During surgery, gall bladder tissue, plasma, peritoneal fluid, and bile fluid samples were obtained at approximately the same time. Thirty-three patients had data acceptable for analysis. Values are given as mean +/- standard deviation. The mean delta time (defined as the time between the administration of cefepime and the time the samples were obtained) was 8.58 +/- 3.53 h. The values for plasma, peritoneal fluid, bile fluid, and gall bladder tissue concentrations were 7.63 +/- 14.17 micrograms/ml, 5.66 +/- 6.80 micrograms/ml, 15.51 +/- 16.94 micrograms/ml, and 5.36 +/- 6.57 micrograms/gm, respectively. The peritoneal fluid/plasma ratio was 2.10 +/- 2.33, the bile fluid/plasma ratio was 14.44 +/- 31.99, and the gall bladder tissue/plasma ratio was 1.44 +/- 1.82. There was a significant correlation between peritoneal fluid and plasma concentration (r = 0.91, p less than 0.0005), and gall bladder tissue and plasma concentration (r = 0.90, p less than 0.0005). There was no correlation between bile fluid and plasma cefepime concentrations. The minimum inhibitory concentration (MIC) data from previous in vitro studies indicate that cefepime concentrations achieved in this patient population would be adequate against typical biliary tract pathogens.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acute Disease; Adult; Ascitic Fluid; Bile; Cefepime; Cephalosporins; Cholecystectomy; Cholecystitis; Female; Gallbladder; Humans; Injections, Intravenous; Male; Middle Aged; Premedication; Regression Analysis

Topics: Acute Disease; Anti-Bacterial Agents; Cefepime; Cephalosporins; Diagnosis, Differential; Drug Hypersensitivity Syndrome; Glucocorticoids; Humans; Male; Middle Aged; Nephritis, Interstitial; Prednisone

Melioidosis is caused by the Gram-negative bacillus Burkholderia pseudomallei. Most clinical reports of disease are from south-east Asia and northern Australia. The organism is intrinsically resistant to most commonly available antibiotics. Standard therapy includes ceftazidime either alone or in combination with co-trimoxazole. The clinical advantage in adding co-trimoxazole has never been determined; nor has the activity of newer, fourth-generation cephalosporins, such as cefepime, been studied in the treatment of this condition. BALB/c mice have been shown to represent an animal model of melioidosis. This animal model was used in this study to compare the efficacy of ceftazidime and cefepime alone or with co-trimoxazole, in the therapy of melioidosis. Antibiotic levels in the mice were determined by HPLC, and dosing was modified to keep plasma antibiotic levels at or above the MIC for the organism-antibiotic combination for a significant part of a 12 h period. Bacterial load, as determined by splenic counts, showed that ceftazidime in combination with co-trimoxazole was the most effective therapeutic option. The animal model described in this study can be used as a preliminary evaluation of therapeutic options for melioidosis.

Topics: Acute Disease; Animals; Anti-Bacterial Agents; Anti-Infective Agents; Cefepime; Ceftazidime; Cephalosporins; Disease Models, Animal; Drug Therapy, Combination; Injections, Intraperitoneal; Melioidosis; Mice; Mice, Inbred BALB C; Trimethoprim, Sulfamethoxazole Drug Combination

The preventive effects of granulocyte colony-stimulating factor, cefephim, and sucralfate on bacterial translocation in experimentally induced acute pancreatitis were investigated. Forty male Wistar albino rats were used in this study. For each rat, the pancreatobiliary ductus was ligated and hence acute pancreatitis was induced. In the control group, no further procedure was performed. Meanwhile, cefephim as an antibiotic, filgrastim, which is a colony-stimulating factor, and sucralfate were given to the other groups at the specified doses. To inhibit bacterial translocation by preserving the bowel barrier, sucralfate, which is known to have a cytoprotective effect on the gastrointestinal system, was used in high doses. Cefephim 30 mg/kg per day (intramuscularly) in group II, filgrastim 10 mg/kg per day (subcutaneously) in group III, and sucralfate 50 mg/kg per day by 8-F feeding tube gavage into the stomach in group IV were given. The number of bacteria translocated into the mesenteric lymph nodes, pancreas, liver, and spleen in the control group significantly increased in comparison with the other groups (P < 0.05). The average number of leukocytes (per mm3) in the control group was significantly higher than that of other groups (P < 0.0001). Regarding the average serum amylase levels, the values of all groups clearly decreased in comparison with the control group (P < 0.0001). Although in the cefephim, filgrastim, and sucralfate groups, (+) pancreatitis was generally seen, in the control group (+++) pancreatitis was detected. Bacterial translocation to the mesenteric lymph nodes and pancreas was partially prevented by filgrastim and sucralfate, and was completely prevented by cefephim. We conclude that in the management of acute pancreatitis, the use of the prophylactic antibiotics, sucralfate and filgrastim, may be advantageous.

Topics: Acute Disease; Animals; Bacterial Translocation; Cefepime; Cephalosporins; Gastrointestinal Agents; Granulocyte Colony-Stimulating Factor; Liver; Lymph Nodes; Male; Pancreas; Pancreatitis; Rats; Rats, Wistar; Spleen; Sucralfate

Topics: Acute Disease; Aged; Bacteremia; Cefepime; Cephalosporins; Cholangiography; Cholangiopancreatography, Endoscopic Retrograde; Cholecystectomy; Cholecystitis; Enterobacteriaceae Infections; Gentamicins; Hafnia alvei; Humans; Liver Abscess; Male; Netilmicin; Suppuration; Treatment Outcome