A randomized, controlled trial of parenteral clindamycin in neonatal necrotizing enterocolitis. Treatment of intra-abdominal infections is appropriate with single-agent or combination antibiotic therapy. Antimicrobial resistance associated with the treatment of bacterial vaginosis. [Antibiotic use in necrotizing pancreatitis. Results of a controlled study]. Efficacy of two comparative antibiotic regimens in the treatment of serious intra-abdominal infections: results of a multicenter study. Adjunctive clindamycin therapy for preterm labor: results of a double-blind, placebo-controlled trial. One-dose antibiotic prophylaxis against wound infection after appendicectomy: a randomized trial of clindamycin, cefazolin sodium and a placebo. Adjunctive antimicrobial therapy for complicated appendicitis: bacterial overkill by combination therapy. Prophylactic antibiotic treatment in patients with predicted severe acute pancreatitis: a placebo-controlled, double-blind trial.
For an assessment of the efficacy of clindamycin in preventing bowel necrosis (intestinal gangrene or perforation), 42 premature infants with radiographically confirmed necrotizing enterocolitis (NEC) (pneumatosis, intraportal gas, or both) were randomly assigned to receive parenterally either ampicillin and gentamicin (control group, n = 22) or ampicillin, gentamicin, and clindamycin (n = 20), 20 mg/kg/d at 8-hour intervals for 10 to 14 days. Infants who had received antibiotics for greater than 24 hours before randomization and those developing intestinal gangrene or perforation less than 12 hours after randomization were excluded. Intestinal gangrene or perforation developed in four infants in the control group and six in the clindamycin group. Four in each group died of NEC. In the control group, one of 18 survivors developed a late stricture requiring surgical resection, whereas six of 15 survivors in the clindamycin group developed such strictures (P = 0.022). Routine inclusion of clindamycin in medical treatment of NEC does not reduce the frequency of intestinal gangrene or perforation and may be associated with an increase in late stricture formation. In a prospective, randomized, single-blind trial, we studied 112 adults with intra-abdominal infections and compared antibiotic therapy with cefoxitin plus placebo to therapy with tobramycin plus clindamycin. Seventy-five percent of patients receiving tobramycin-clindamycin and 71% of those receiving cefoxitin-placebo had either shock, bacteremia, malnutrition, alcoholism, rapidly or ultimately fatal underlying disease, infection originating from the distal small bowel or colon, or had had failed therapy before treatment ("high-risk" group). One third of the patients in both groups grew bacteria in the initial culture resistant to the antibiotic regimen used. Ten patients receiving cefoxitin-placebo (17%) and 11 receiving tobramycin-clindamycin (21%) had recurrence of infection or died of infection (clinical failures). Nineteen failures occurred in high-risk patients (p less than 0.05) and 17 were in patients that had antibiotic-resistant bacteria in the initial culture (p less than 0.01). Adverse effects were rare and remitted after antibiotics were stopped. Our results suggest that both cefoxitin and tobramycin-clindamycin are appropriate antibiotic regimens to treat intra-abdominal infections. Clinical failure is more common in high-risk patients and when antibiotic-resistant organisms are isolated from initial cultures. This study was undertaken to evaluate antimicrobial susceptibility of vaginal anaerobic bacteria before and after treatment of bacterial vaginosis.
                A randomized clinical trial of 119 nonpregnant women with bacterial vaginosis receiving either intravaginal metronidazole for 5 days or clindamycin for 3 days was performed. Women had 1 baseline and 3 follow-up visits at which quantitative vaginal cultures were performed. Anaerobic isolates underwent antimicrobial susceptibility testing.
                Complete susceptibility data was available on 95 women (47 metronidazole and 48 clindamycin). Of 1059 anaerobic bacterial isolates, less than 1% demonstrated resistance to metronidazole. In contrast, 17% demonstrated baseline clindamycin resistance, and 53% demonstrated resistance to clindamycin after therapy. Women exposed to clindamycin (but not metronidazole) had high frequencies (80%) of clindamycin-resistant anaerobic bacteria that persisted for 90 days after treatment.
                Treatment of bacterial vaginosis with clindamycin is associated with marked evidence of antimicrobial resistance among vaginal anaerobic bacteria. This may increase the vaginal reservoir of macrolide-resistant bacteria. The clinical course and death rate in acute necrotizing pancreatitis (ANP) are largely determined by septic complications as part of bacterial invasion of the necrotic tissues. It remains unclear whether antibiotic prophylaxis reduces bacterial invasion of the necroses or septic complications. It was, therefore, the aim of this study to evaluate the effect of prophylactic administration of antibiotics to patients with ANP.
                In a prospective randomized study 13 patients with ANP and sterile necroses (quantified by contrast-enhanced computed tomography) were given twice daily 200 mg ofloxacin and twice daily 500 mg metronidazole intravenously. The results were compared to those in a control group of patients with ANP (n = 13) who had not initially received antibiotics. In both patient groups fine-needle biopsies of the necrotic areas were performed on days 1, 3, 5, 7 and 10. If there was evidence of infection, antibiotics were then also given to patients of the control group.
                The extent of the necroses was the same, 40%, in both groups. These necroses became infected in a median of 9.5 (treated group) and 10 days (untreated group). The clinical course, documented by the APACHE II score, showed significant improvement under antibiotic treatment (days 1-5-10: scores 15-13.0-9.5). In the (initially untreated) control group the clinical condition deteriorated significantly (days 1-5-10: score 11.5-15.0-16.0). The changes from days 1 to 5, 5 to 10 and 1 to 10 were highly significant (Wilcoxon test, P < 0.01). None of the patients in the antibiotic group died within the first 3 weeks, but 2 of the 13 in the control group died.
                Antibiotic prophylaxis neither prevented nor delayed bacterial infection of the necrotic pancreas. But it significantly improved the clinical course if started before the onset of infection of the pancreatic necroses. A multicenter, open-label randomized trial was conducted to evaluate the efficacy and tolerability of monotherapy with imipenem-cilastatin (I-C) compared with combination therapy with clindamycin and an aminoglycoside (C+A) for treatment of 117 patients with serious intra-abdominal infections. Fifty-three patients (45%) received I-C and 64 patients (55%) received C+A. The overall clinical success rate was 96.2% for the I-C patients and 92.2% for the C+A patients. Clinical failure rates were 3.8% and 7.8%, respectively (P = NS). Eradication or suppression of pathogens was observed in 81.8% and 82.2% of patients, respectively. Uniform bacteriologic response was observed among all infection subgroups. Fourteen of 145 patients experienced adverse symptoms, including six of 66 (9.1%) monotherapy patients and eight of 79 (10.1%) combination-therapy patients (P = NS). The results of this study demonstrate that I-C monotherapy was as effective as C+A combination therapy for the treatment of serious intra-abdominal infections, regardless of the site or severity of infection or the clinical status of the patient. Both regimens also were found to be comparable in tolerability. A double-blind, placebo-controlled, randomized trial was conducted to evaluate the efficacy, safety, and tolerance of a course of clindamycin (administered for 3 days intravenously and 4 days orally) among hospitalized women with preterm labor at less than or equal to 34 weeks' gestation who were treated with tocolytics. One hundred three woman-perinate pairs were analyzed. Univariate analysis demonstrated that pregnancies were continued longer in women treated with clindamycin than in women who received placebo (clindamycin-treated group, 35 days; placebo-treated group, 25 days; p = 0.02). Survival analysis showed that pregnancy continued at least 35.5 days in 50% of clindamycin-treated women versus 20 days for control women (p = 0.03). Obstetric and microbiologic parameters associated with treatment outcomes were also sought. Women with bacterial vaginosis more often delivered preterm (p = 0.03; relative risk, 1.4; 95% confidence interval, 1.04 to 2.0). Among women with bacterial vaginosis, trends for increased duration of pregnancy (clindamycin-treated group, 36 days; placebo-treated group, 19 days), increased birth weight (clindamycin-treated group, 2634 gm; placebo-treated group, 2256 gm), and increased mean gestational age at delivery (clindamycin-treated group, 35 weeks; placebo-treated group, 34 weeks) were associated with clindamycin treatment. Women with either group B streptococcus, Chlamydia trachomatis, Trichomonas vaginalis, or Staphylococcus aureus were more likely to have preterm premature rupture of membranes (p = 0.01). Clindamycin treatment of these women reduced the incidence of preterm premature rupture of membranes to that of uninfected subjects. Stratification by gestational age at enrollment showed clindamycin treatment to be associated with an increased interval to delivery only among mothers enrolled before 33 weeks' gestation (clindamycin-treated group, 40 days; placebo-treated group, 28 days; p less than 0.05). Treatment with clindamycin appeared safe and well tolerated, with benefits limited to women who were less than or equal to 32 weeks' gestation. Two hundred and fifty patients were admitted to a prospective randomized trial of single dosage prophylaxis against wound infection after appendicectomy. There were 12 exclusions, 72 patients received placebo, 81 received 600 mg i.m. clindamycin phosphate and 85 received 1 1 g i.m. cefazolin sodium, the agent being given in the anaesthetic room. Clindamycin produced a significant reduction in the overall rate of wound infection from 33 per cent in the controls to 17 per cent. In cases with a gangrenous or perforated appendix the infection rate in controls was 78 per cent; this was reduced to 44 per cent by a single dose of clindamycin. Cefazolin significantly reduced the number of aerobic organisms isolated from wound infections, but did not significantly reduce the incidence of wound infection. We conclude that anaerobic organisms are more important than faecal aerobic organisms in the pathogenesis of wound infection after appendicectomy. Although single antimicrobials with broad-spectrum aerobic and anaerobic coverage are effective in patients with appendicitis, many general surgeons continue to use multiple agents. A prospective, double-blind, randomized trial was designed to detect any clinical correlate of in vitro susceptibility advantage of multiple antimicrobials as adjunctive therapy for 114 patients undergoing operation for complicated appendicitis. There was clinical resolution of intraabdominal infections with no occurrence of postoperative infectious complications in 90% (36 of 40) of the cefotetan group and 86% (31 of 36) of the clindamycin/amikacin group (p = 0.11). The number of patients who had changes in antibiotic therapy due to postoperative complications was higher in the clindamycin/amikacin group: five (12.5%), compared to one (2.8%) in the cefotetan group (p = 0.07). Although Bacteroides fragilis group organisms resistant to cefotetan were identified, none was responsible for the postoperative infections. Adverse drug events in 28% of the cefotetan group and 26% of the clindamycin/amikacin group consisted primarily of transient elevations of liver function tests. Monotherapy with a second-generation, broad-spectrum cephalosporin, such as cefotetan, given twice a day is an economical and effective adjunctive regimen in patients with complicated appendicitis for which operation is the definitive treatment. Aminoglycosides and other, more potent antimicrobials should be reserved for resistant organisms or nosocomial infections. Antibiotic prophylaxis in necrotizing pancreatitis remains controversial. Until now, there have been no double-blind studies dealing with this topic.
                A total sample size of 200 patients was calculated to demonstrate with a power of 90% that antibiotic prophylaxis reduces the proportion of patients with infected pancreatic necrosis from 40% placebo (PLA) to 20% ciprofloxacin/metronidazole (CIP/MET). One hundred fourteen patients with acute pancreatitis in combination with a serum C-reactive protein exceeding 150 mg/L and/or necrosis on contrast-enhanced CT scan were enrolled and received either intravenous CIP (2 x 400 mg/day) + MET (2 x 500 mg/day) or PLA. Study medication was discontinued and switched to open antibiotic treatment when infectious complications, multiple organ failure sepsis, or systemic inflammatory response syndrome (SIRS) occurred. After half of the planned sample size was recruited, an adaptive interim analysis was performed, and recruitment was stopped.
                Fifty-eight patients received CIP/MET and 56 patients PLA. Twenty-eight percent in the CIP/MET group required open antibiotic treatment vs. 46% with PLA. Twelve percent of the CIP/MET group developed infected pancreatic necrosis compared with 9% of the PLA group (P = 0.585). Mortality was 5% in the CIP/MET and 7% in the PLA group. In 76 patients with pancreatic necrosis on contrast-enhanced CT scan, no differences in the rate of infected pancreatic necrosis, systemic complications, or mortality were observed.
                This study detected no benefit of antibiotic prophylaxis with respect to the risk of developing infected pancreatic necrosis.
There was insufficient evidence to recommend a particular antibiotic regimen for the treatment of NEC. There were concerns about adverse effects following the usage of clindamycin, related to the development of strictures. To address this issue a large randomised controlled trial needs to be performed.