Ceftriaxone versus combined gentamicin and clindamycin for polymicrobial surgical sepsis.

During a 7 month trial for therapy of polymicrobial surgical sepsis, intravenous antibiotic treatment was randomized between gentamicin (1 mg/kg every 8 hours) plus clindamycin (8 mg/kg every 6 hours), and the cephalosporin, ceftriaxone (1 g every 12 hours) in 197 patients, of whom 99 were being treated for peritonitis, 93 for soft tissue sepsis, and 5 for other forms of infection. No significant differences were noted in patient demographics, type of sepsis, associated disease states, surgical procedure, or causative aerobic or anaerobic pathogens. Results demonstrated approximately equivalent efficacy, although cure rates obtained with ceftriaxone in patients with soft tissue sepsis or intraabdominal abscess were superior to those achieved with combination gentamicin and clindamycin. There were no significant side effects with ceftriaxone therapy, such as the renal failure noted in six of the patients treated with gentamicin and clindamycin. We conclude that single agent treatment with ceftriaxone is preferable because of the greater safety and the longer dosing intervals.

Clinical comparison of cefotaxime with gentamicin plus clindamycin in the treatment of peritonitis and other soft-tissue infections.

The efficacy and safety of cefotaxime were compared with the efficacy and safety of gentamicin plus clindamycin in the treatment of peritonitis and soft-tissue infection in 112 patients. Patients received 20 mg of intravenous cefotaxime/kg of body weight every 6 hr or 1 mg of gentamicin/kg every 8 hr plus 5 mg of clindamycin/kg every 6 hr (both intravenously). Therapy was continued for five to 10 days. The overall clinical cure rate was 82%, with no significant difference between cure rates in the two groups. Both antibiotic regimens were effective against aerobic and anaerobic isolates, although Pseudomonas aeruginosa, an occasional isolate of Enterobacter, and some anaerobes were resistant to cefotaxime. All clinical failures involved patients who had septicemia or who had received inadequate surgical treatment. Six (11%) of the patients who received combination therapy developed impaired renal function, as indicated by a rise in serum creatinine of 30%. No reduction in renal function was noted in patients given cefotaxime. The clinical efficacy of cefotaxime was equal to that of gentamicin plus clindamycin, and less nephrotoxicity was encountered with cefotaxime.

Clinical evaluation of cefotaxime versus gentamicin plus clindamycin in the treatment of polymicrobial peritonitis.

One hundred fifty-one patients with presumed aerobic-anaerobic mixed peritoneal infections were treated in a prospective, randomized trial with either cefotaxime alone (76) or the combination of gentamicin-clindamycin (75). Primary and complicating foci of sepsis were cultured for both aerobic and anaerobic pathogen identification and antibiotic susceptibility. In vitro aerobic disk sensitivities (114 isolates) to cefotaxime were 82% and to gentamicin, 88%; anaerobic agar-diffusion sensitivities (227 isolates) to cefotaxime were 87% and to clindamycin, 98%. Only enterococci and Pseudomonas sp were consistently resistant to cefotaxime. Infection was eliminated in 82% of those treated with cefotaxime and in 87% of those treated with the gentamicin-clindamycin combination, yet sepsis recurred in 11% of those treated with cefotaxime and in 13% for those given gentamicin-clindamycin. Five patients (7%) demonstrated nephrotoxicity for gentamicin. (Serum creatinine increased greater than 1.5 mg/100 ml over pretreatment levels.) Otherwise, incidence and severity of adverse reactions were identical for the two groups and consisted primarily of phlebitis and diarrhea. One patient in each treatment group died of uncontrolled sepsis. Although results suggested a laboratory superiority of gentamicin-clindamycin, there was a clinical equality in therapeutic benefit and a greater safety following the use of cefotaxime alone.

Clinical comparison of cefotaxime versus the combination of gentamicin plus clindamycin in the treatment of polymicrobial soft-tissue surgical sepsis.

The safety and efficacy of cefotaxime versus a combination of gentamicin and clindamycin were compared in a prospective, randomized study of 98 surgical patients with polymicrobial soft-tissue infection or septicemia. Forty-nine patients received cefotaxime (20 mg/kg every six hours), and 49 received gentamicin (1 mg/kg every eight hours) plus clindamycin (5 mg/kg every six hours); all drugs were given intravenously. Overall, there was no statistical difference in clinical response to the two regimens, infection being eliminated in 73% of the patients treated with cefotaxime and 71% of those given gentamicin plus clindamycin. Adverse effects were mild and self-limited in both treatment groups, although three patients treated with gentamicin plus clindamycin experienced some loss of renal function. Most aerobic gram-negative rods were sensitive to both cefotaxime and gentamicin, but anaerobes were slightly more sensitive to clindamycin than to cefotaxime. Cefotaxime appeared to be at least as effective as gentamicin plus clindamycin in the treatment of polymicrobial soft-tissue infections and septicemia, and, in light of the loss of renal function associated with the gentamicin-clindamycin regimen, somewhat safer. The high failure rate among patients on both regimens with septicemia of unknown origin (five of the nine treated with cefotaxime and two of the four treated with gentamicin and clindamycin), however, indicates the critical role of surgical management in the treatment of polymicrobial soft-tissue sepsis.

Bacteriologic considerations in perforated necrotizing enterocolitis.

During a ten-year period, 61 infants with perforated necrotizing enterocolitis were managed by bowel resection, enterostomy, and intravenous antibiotics. Aerobic and anaerobic cultures were taken of venous blood, from the peritoneal cavity at operation, and of any subsequent wound and/or intraperitoneal infection. No significant differences between fatal and nonfatal cases were noted with respect to presence of anaerobes in the peritoneal flora (six babies with two deaths) or culture-confirmed bacteremia (73% of the total). However, peritonitis participated in by Pseudomonas aeruginosa (ten babies), or beta-hemolytic streptococcus (five babies) was -niformly lethal, as were complicating bacteremias due to P aeruginosa, beta-hemolytic streptococcus, and Staphylococcus aureus (two each). Anaerobic peritoneal isolates (all gram-positive cocci) were never noted if performation occurred before the eighth day of life; they did not appear to adversely affect survival. Based upon these data, antibiotic therapy should include either gentamicin or tobramycin, with penicillin, until subsequent culture reports dictate otherwise.

Prophylactic and preventive antibiotic therapy: timing, duration and economics.

Previous studies have demonstrated that administered antibiotics must be active against major anticipated pathogens and must have reached sufficient concentrations in the tissue or body fluid at risk by the time of bacterial challenge if prophylactic therapy is to be maximally effective in reducing the infection rate of potentially contaminated surgery. The need for continuing antibiotic prophylaxis beyond the day of operation, however, has been uncertain. In a prospective, randomized, double-blind study of 220 patients undergoing elective gastric, biliary or colonic surgery, perioperative administration of cefamandole plus five days of placebo was compared to perioperative plus five days of postoperative antibiotic therapy; no significant difference was found between the groups in the rate of infection of wound (6 and 5%, respectively), peritoneum (2% each) and elsewhere (6% and 5%). In another prospective, randomized, nonblind study of 451 determinant cases of 1,624 patients undergoing emergency laparotomy, cephalothin was instituted preoperatively but after peritoneal contamination had occurred (i.e., abdominal trauma, etc.); continued postoperative antibiotic again failed to reduce further the wound and peritoneal infection rates, as noted on comparing perioperative therapy alone (infection rates 8 and 4%, respectively) with perioperative plus 5-7 days of postoperative treatment (10% and 5%, respectively). Analysis of these data, as well as of the extra expenses incurred by 463 patients because of infection in a previous prophylactic antibiotic study, revealed an average additional expenditure of $2,686.00 for each instance of postoperative infection of the wound and/or peritoneum; whereas savings of $300.00 per patient at risk were obtained whenever appropriate prophylactic antibiotic had been given.

Cefamandole in treatment of peritonitis.

Cefamandole was evaluated as the sole antimicrobial agent used to treat bacterial peritonitis in 113 patients. Dosage varied between 1 and 2 g given intravenously every 6 hr. Laparotomy for excision of infected or gangrenous tissues, closure of gastrointestinal perforations, or drainage of an established abscess was required in 99 of the cases. A good clinical response was obtained in 107 patients, or 95% of the total group. Of the six deaths only one could be attributed to infection. No evidence of renal, hepatic, or hematopoietic toxicity was noted. There were no allergic reactions, although 13 patients (12%) developed phlebitis in a vein used for antibiotic administration. Bacteriological studies revealed aerobic peritonitis in 99% of the patients, with anaerobe participation in 60% of these cases. Sensitivity testing by the disk diffusion and tube dilution methods confirmed the appropriateness of cefamandole therapy; 91% of the gram-negative rods and 61% of the anaerobes were susceptible. From results of this study, it would appear that cefamandole is a reliably effective antibiotic for use in treatment of most forms of acute peritonitis. Its role in surgical prophylaxis may be even more promising.

Antibiotic prophylaxis in gastric, biliary and colonic surgery.

Antibiotic prophylaxis for surgery has appeared indicated whenever likelihood of infection is great or consequences of such are catastrophic. For better clarification, a prospective, randomized, double-blind study was run on 400 patients undergoing elective gastric, biliary, and colonic operations. There were four treatment categories, with antibiotic being instituted 12 hours preoperatively, just prior to operation, after operation, or not at all. During operation, samples of blood, viscera, muscle, and fat were taken for determination of antibiotic concentration. Both aerobic and anareobic cultures were also taken of any viscus entered, peritoneal cavity, and incision. Similar cultures were run on all postoperative infections. Results demonstrated that the incidence of wound infection could be reduced significantly by the preoperative administration of antibiotic in operations on the stomach (22% to 4%), on the biliary tract (11% to 2%), and large bowel (16% to 6%). Less impressive results were obtained for peritoneal sepsis. Initiation of antibiotic postoperatively gave an almost identical infection rate as if antibiotic had not been given (15% and 16%, respectively).

Use of aminoglycosides in surgical infections.

Most infections on the surgical ward are due to one or more gram-negative rods, acting either as the sole pathogens or as principal components in a polymicrobial flora. To date, parenteral aminoglycosides have proven to be the most effective antibiotics for control or treatment of such sepsis. Unfortunately, however, serious complications as well as therapeutic failures do occur. During a 40-month period, 405 surgical patients receiving aminoglycosides (Gentamicin, Tobramycin, Sisomicin, or Amikacin) were prospectively studied with respect to: indications for antibiotic; patient population; serum concentrations of antibiotic according to route of administration, dose in mg/kg/day, and renal function; rapidity of antibiotic excretion in the urine; causative bacteria and their sensitivities to each aminoglycoside as determined by both disc and tube dilution methods; severity and frequency of drug complications; and clinical efficacy of each study antibiotic. Results supported the contention of a superior effectiveness from aminoglycosides for established abdominal and unspecified surgical infections, more rapid development of therapeutic blood levels by intravenous administration, need to alter drug dose according to frequent serum creatinine determinations, increased drug toxicity in dehydrated and shocked patients, preventability of complicating Candida sepsis, and the importance of early as well as adequate surgical debridement and drainage.

Treatment of surgical infections with tobramcin.

A survey of the safety and effectiveness of tobramycin, a newly developed aminoglycoside antibiotic, was assessed in 116 septic surgical patients. For comparison, the final 52 cases were randomized with 51 similarly infected patients who were treated with gentamicin. The two antibiotics gave equally good results when evaluated bacteriologically and clinically. Nevertheless, gram-negative infections appeared more likely to be susceptible to tobramycin than to gentamicin. No toxicity to the liver or bone marrow was observed. Although there were 13 cases of nephrotoxicity and 4 of ototoxicity, only one instance of such an adverse drug reaction could be attributed to parenterally administered aminoglycoside alone. In fact, topical neomycin and established renal damage caused by prior episodes of shock or dehydration appeared to be significantly more responsible for such adverse effects.

Incidence and significance of intraperitoneal anaerobic bacteria.

To amplify recent interest in anaerobic infections following abdominal disease, trauma, or surgery, 512 consecutive patients subjected to emergency celiotomy had both aerobic and anaerobic cultures taken of peritoneal fluid as well as all complicating wound and intra-abdominal infections. Average time between peritoneal entry of abscess drainage and specimen incubating under anaerobic conditions was less than two minutes. During 4 of the seven study months, patients had antibiotic therapy randomized, with clindaymcin or cephalothin being sole parenteral agents and given intravenously prior to operation and for 5 days thereafter. Results demonstrated that anaerobes uniformly contaminate the peritoneal cavity whenever distal or obstructed intestine has been perforated, irrespective of the cause. Although all but one of the 123 complicating wound and intra-abdominal infections were due solely or at least in part to aerobic pathogens, 2/3 of such infections also contained one or more different anaerobic species acting in synergism with the aerobes. No significant difference in incidence of postoperative infection or in infecting bacteria could be found with respect to antibiotic administered or etiology of perforation. Indeed, duration of bacterial exposure to atmospheric oxygen was the most critical factor influencing culture recoverability of anaerobic organisms, likelihood of ensuing wound or peritoneal sepsis participated in by an anaerobe, and success in control of established infections harboring anaerobes.