cefepime and Appendicitis

To evaluate the safety and efficacy of cefepime hydrochloride plus metronidazole vs the combination of imipenem and cilastatin sodium in the treatment of complicated intra-abdominal infections in adult patients.. Prospective, randomized, double-blind multicenter study.. University-affiliated hospitals in the United States and Canada.. Three hundred twenty-three patients with complicated intra-abdominal infections in whom an operative procedure or percutaneous drainage was required for diagnosis and management.. Cefepime, 2 g, was administered intravenously every 12 hours (n= 164) in addition to metronidazole, 500 mg (or 7.5 mg/kg) intravenously every 6 hours. Imipenen-cilastatin sodium, 500 mg, was administered intravenously every 6 hours (n= 159). Surgical infection management was determined by the patients' surgeons. MAIN OUTCOME ASSESSMENTS: Clinical cure, defined as elimination of all signs and symptoms relevant to the original infection; and treatment failure, defined as persistence, increase or worsening of signs and symptoms resulting in an antibiotic change, requirement of an additional surgical procedure to cure the infection, or a wound infection with fever.. Of the initial isolates, 84% were susceptible to cefepime and 92% were susceptible to imipenem-cilastatin. Among the 217 protocol-valid patients, those treated with cefepime+metronidizole were deemed clinical cures (88%) more frequently than were imipenem-cilastatin-treated patients (76%) (P=.02). Using multivariate analysis to adjust for identified clinical risk factors for an adverse outcome (severity of presenting illness, isolation of enterococcus, type of infection, and duration of prestudy hospitalization), there was a trend (P=.06) toward a higher cure rate favoring cefepime+metronidazole. Pathogens were eradicated in significantly (P=.01) more patients treated with combined cefepime and metronidazole (89%) than with imipenem-cilastatin (76%).. The combination of cefepime plus metronidazole is safe and effective therapy for patients with severe intra-abdominal infections.

Topics: Abdomen; Abdominal Abscess; Adult; Aged; Antitrichomonal Agents; Appendicitis; Cefepime; Cephalosporins; Cilastatin; Double-Blind Method; Drug Therapy, Combination; Female; Gastrointestinal Diseases; Humans; Imipenem; Infections; Male; Metronidazole; Middle Aged; Peritonitis; Treatment Outcome

Many antibiotics and antibiotic combinations are used for the treatment of peritonitis because of advanced (gangrenous or perforated) appendicitis. An aminoglycoside combined with an antianaerobe antibiotic is one standard treatment, but there is concern about the potential nephrotoxicity of the aminoglycoside and the necessity for monitoring aminoglycoside blood levels. Cefepime, a new broad-spectrum cephalosporin with a prolonged serum half-life, has excellent activity against gram-positive and gram-negative bacteria, including Pseudomonas aeruginosa. Its spectrum of activity is similar to the aminoglycosides, but it has less potential for inducing renal injury. A double-blind, randomized study compared cefepime, 2 grams every 12 hours IVPB plus metronidazole 0.5 grams every eight hours IVPB (C/M) with gentamicin 1.5 milligrams per kilograms of IVPB plus clindamycin 0.9 grams q eight hours IVPB (G/C), administered up to 14 days, in 96 surgically treated patients with gangrenous or perforated appendicitis. Fifty patients had advanced appendicitis (nine gangrenous and 41 perforated) in the C/M group and 46 patients (six gangrenous and 40 perforated) in the G/C group. The mean number of days of postoperative fever (C/M, 4.4 +/- 2.7 versus G/C, 5.0 +/- 2.2), postoperative hospitalization (C/M, 2.0 +/- 1.9 versus G/C, 2.0 +/- 2.1) and antibiotic therapy (C/M, 6.3 +/- 1.9 versus G/C, 6.9 +/- 1.9) was similar in the two treatment groups. There were 11 treatment failures (C/M, three; G/C, eight; p = 0.13), six of which were probably a result of enterococci. No deaths occurred. Our study results show that the efficacy of cefepime plus metronidazole is equivalent to that of clindamycin plus gentamicin.

Topics: Adolescent; Adult; Appendicitis; Cefepime; Cephalosporins; Clindamycin; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Female; Gentamicins; Humans; Male; Metronidazole; Middle Aged; Treatment Outcome

Cefepime is a new extended-spectrum cephalosporin with gram-positive and gram-negative coverage including Staphylococcus aureus and Pseudomonas aeruginosa. We evaluated the drug's plasma, peritoneal fluid, and appendix tissue concentrations in patients with a postoperative diagnosis of perforated or gangrenous appendicitis. Patients 18 years of age or older were randomly assigned to receive either cefepime 2 g every 12 hours plus metronidazole 500 mg every 6 hours intravenously, or gentamicin 1.5 mg/kg plus clindamycin 900 mg every 8 hours intravenously. During surgery, appendix tissue, plasma, and peritoneal fluid samples were obtained, and frozen at -70 degrees C for high-pressure liquid chromatographic analysis. Thirty-five patients with perforated (26) or gangrenous (9) appendicitis had concentrations acceptable for analysis. The mean time between the administration of cefepime and the time of sampling (referred to as delta time) was 5.99 +/- 3.75 hours (mean +/- SD). The values for plasma (n = 34), tissue (n = 33), and peritoneal fluid (n = 25) concentrations were 16.27 +/- 21.87 micrograms/ml, 4.84 +/- 6.15 micrograms/g, and 14.4 +/- 22.84 micrograms/ml, respectively. The appendix tissue:plasma ratio was 0.66 +/- 0.52 and the peritoneal fluid:plasma ratio was 0.66 +/- 0.51. Spearman rank correlations indicated statistically significant correlations between plasma concentration (r = -0.889; p less than 0.0001), peritoneal fluid concentration (r = -0.783; p = 0.0002), and appendix tissue concentration (r = -0.704; p = 0.0016) versus delta time.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adolescent; Adult; Appendectomy; Appendicitis; Appendix; Ascitic Fluid; Cefepime; Cephalosporins; Clindamycin; Female; Gangrene; Gentamicins; Humans; Injections, Intravenous; Intestinal Perforation; Male; Metronidazole; Rupture, Spontaneous

Institutional protocols for preincisional antibiotic prophylaxis can standardize care and improve outcomes. However, challenges remain in compliance with such protocols for urgent or emergent operations. We hypothesized that compliance with an institutional protocol for antibiotic prophylaxis for appendectomy for appendicitis in pediatric patients results in reduced surgical site infections (SSIs) after simple appendectomy.. This retrospective study assessed all pediatric patients (≤18 y) who underwent appendectomy for confirmed simple appendicitis at a tertiary children's hospital between 2012 and 2015. Demographic, admission, and outcome data were recorded. Compliance with the protocol was assessed. Univariate analyses were performed to identify factors associated with any SSI and protocol noncompliance.. Overall compliance with antibiotic prophylaxis occurred in 590 of 697 patients (85%). Compliance was high with timing (91%), spectrum (95%), and protocol-recommended drug (87%). Admission antibiotics alone were administered in 65 patients (9%), preincisional antibiotics alone in 254 patients (36%), and both in 378 patients (55%). Patients included in the analysis received a median of 2 (range 1-6) doses of antibiotics preoperatively. Ten patients (1.4%) developed an SSI. Only receipt of any antibiotics within an hour of incision was associated with decreased odds of SSI (odds ratio 0.22, 95% confidence interval 0.06-0.87). No factors were associated with noncompliance.. An institutional appendicitis protocol yields high compliance with prophylactic antibiotic administration and associated low SSI rates, but at a cost of antibiotic over-administration. Further efforts are necessary to sustain compliance while also practicing appropriate antibiotic stewardship.

Topics: Adolescent; Anti-Bacterial Agents; Antibiotic Prophylaxis; Appendectomy; Appendicitis; Cefepime; Cephalosporins; Child; Child, Preschool; Drug Therapy, Combination; Female; Follow-Up Studies; Guideline Adherence; Humans; Infant; Infant, Newborn; Logistic Models; Male; Metronidazole; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Practice Guidelines as Topic; Preoperative Care; Retrospective Studies; Surgical Wound Infection; Treatment Outcome