Ceftazidime/clindamycin versus tobramycin/clindamycin in the treatment of intra-abdominal infections

In order to assess the efficacy and toxicity of ceftazidime as a substitute for aminoglycosides in the treatment of intra-abdominal sepsis, a prospective randomized trial was conducted. Ninety-four patients (49% trauma) were randomized to receive ceftazidime/clindamycin (CAZ/C) (n = 47) or tobramycin/clindamycin (T/C) (n = 47). CAZ (2.0 gm) and C (0.9 gm) were administered intravenously every 8 hours while T dosage was adjusted to maintain peak (5-8 mg/L) and trough (less than 2 mg/L) concentrations. Age, sex, baseline serum creatinine, and etiology of infection were comparable in the two groups. Clinical cure was similar in culture-positive and culture-negative patients who received CAZ/C (94% vs 88%). The clinical cure rate however was significantly lower in the T/C culture positive (73%) than in the culture negative patients (100%) (P = 0.016). Pathogenic organisms were eradicated in 100% (30/30) and 76% (13/17) of CAZ/C and T/C patients, respectively (P = 0.0006). Nephrotoxicity Nephrotoxicity or ototoxicity was observed in none of the CAZ/C patients and in one and two T/C patients, respectively. CAZ/C more effectively eradicated the bacteria isolated from these patients and no significant difference in clinical response was observed in culture-positive patients. These findings plus the lack of toxicity suggest that CAZ/C is an effective alternative for treatment of IAI.     

Cefoxitin plus tobramycin and clindamycin plus tobramycin. A prospective randomized comparison in the therapy of mixed aerobic/anaerobic infections

The efficacy of therapy with cefoxitin sodium plus tobramycin sulfate, with the tobramycin therapy discontinued if no cefoxitin-resistant pathogens grew from appropriate cultures, was compared with clindamycin phosphate plus tobramycin therapy in mixed aerobic/anaerobic intra-abdominal and female pelvic infections. Of 96 evaluable patients, 39 (76%) of 51 randomized to cefoxitin and 38 (84%) of 45 randomized to clindamycin were cured and an additional seven (14%) of 51 and three (6.7%) of 45, respectively, were improved. Bacteroides fragilis "group" was isolated from 44 (54%) of 82 patients with appropriate specimens. Duration of aminoglycoside therapy was significantly shorter in patients randomized to cefoxitin and tobramycin (mean, 4.1 +/- 1.8 days vs 7.0 +/- 3.2 days). There was a tendency to greater nephrotoxic reactions in patients randomized to clindamycin and tobramycin. We conclude that cefoxitin plus tobramycin with selective early discontinuation of aminoglycoside therapy is an acceptable regimen for the therapy of mixed aerobic/anaerobic infections.     

A randomized clinical trial of moxalactam alone versus tobramycin plus clindamycin in abdominal sepsis.

One hundred patients with intraabdominal infections were assigned randomly in double-blind fashion to receive either the combination of tobramycin plus clindamycin (TM/C) or moxalactam (MOX) alone. Fifty patients comprised each group, but one patient in each group died of infection before 48 hours treatment. In the remaining 98 patients, the average age was 62 years, initial serum albumin was 3.0 mg/dl, serum creatinine was 1.5 mg/dl, and over half of the patients were nutritionally deficient by the prognostic nutritional index criteria. In approximately one-half of the patients, the source of infection was perforated colon or perforated appendix. There were no significant differences in demographic factors between these groups, except that those who were given TM/C were older, while those who were given MOX had a more serious long-term prognosis due to underlying disease. The average length of treatment was 11 days, and the average hospitalization time was 24 days. Clinical response to therapy was identical, since 74% of the TM/C patients and 76% of the MOX patients had satisfactory responses. Bacteria persisted at the site of infection in 63% of the TM/C patients and in 65% of the MOX patients, with the most common isolate being Staphylococcus epidermidis. Pseudomonas infections were the most difficult to cure in both groups. The two regimens differed only in side effects; TM/C was a more frequent (p less than 0.05) cause of nephrotoxicity, and elevated prothrombin time/partial thromboplastin time (PT/PTT) was more frequently (p less than 0.05) observed in MOX. All PT/PTT elevations responded to injections of vitamin K, and no serious bleeding occurred. Choice between these regimens depends on the risk of renal versus hematologic side effects, rather than efficacy.     

A randomized comparison of cefoxitin with or without amikacin and clindamycin plus amikacin in surgical sepsis.

The efficacy of cefoxitin, either alone or in combination (+/-) with an aminoglycoside was compared with clindamycin plus (+), an aminoglycoside for the treatment of mixed aerobic-anaerobic surgical infections, in a prospective randomized single blinded study. One hundred patients were entered into the study; 37 patients were assessable for clinical outcome in both groups, while toxicity could be assessed in 46 patients in the cefoxitin group and 47 in the clindamycin group. The groups were evenly matched considering age, sex, and type of infection. Favorable clinical responses were achieved in 34 of 37 patients treated with cefoxitin +/- amikacin, and 29 of 37 patients treated with clindamycin + amikacin; there was no statistical difference between the groups (p greater than 0.1). The incidences of toxicity were the same. Our study has demonstrated that cefoxitin with or without an aminoglycoside is as effective as clindamycin plus an aminoglycoside in the therapy of serious mixed infections in surgical patients.     

A randomized controlled trial of moxalactam versus clindamycin/tobramycin in the treatment of mixed anaerobic/aerobic infections

Many infections are due to mixtures of facultative gram-negative bacilli and anaerobic bacteria. Moxalactam, a semisynthetic beta lactam antibiotic, is active against a wide range of anaerobic organisms, including most strains of Bacteroides fragilis, as well as many aerobic gram-negative bacilli. We performed a prospective, randomized controlled trial comparing moxalactam alone with the regimen of clindamycin and tobramycin for treatment of mixed aerobic/anaerobic infections. One hundred and six patients with presumed mixed infections were randomized to the study groups. The resultant groups were clinically and microbiologically comparable. The effectiveness of treatment was similar with both antibiotic regimens. Five of 25 patients tested in the moxalactam group had a prolongation of their prothrombin time and one of them developed clinically important bleeding. Two of the 23 patients tested in the clindamycin/tobramycin group had a prolonged prothrombin time with no bleeding. Decreases in hematocrit which could be "probably" or "possibly" related to antimicrobial use were seen in 6 of 48 moxalactam patients and none of 50 clindamycin/tobramycin patients (P = .03). Moxalactam, a potent antimicrobial for both anaerobic and aerobic organisms, demonstrated effectiveness in treating mixed anaerobic/aerobic infections similar to clindamycin/tobramycin but was associated with clinically important decreases in hematocrit.     

Surgically treated gangrenous or perforated appendicitis. A comparison of aztreonam and clindamycin versus gentamicin and clindamycin.

A randomized, double-blinded, controlled clinical study of 84 patients with surgically treated gangrenous or perforated appendicitis was done to compare the efficacy of the combination of aztreonam, the first monobactam antibiotic, with gentamicin when either was combined with clindamycin. Fifty-six patients who were treated with aztreonam and clindamycin (A/C) and 28 patients who were treated with gentamicin and clindamycin (G/C) fulfilled criteria for evaluation. A matched historic control group of 56 G/C patients was also included for comparison. All measures of outcome, including days of fever, hospitalization, antibiotic therapy, and the incidence of antibiotic failures, were similar. It was concluded that aztreonam was as effective as gentamicin in this study and may offer some advantages with regard to toxicity and serum drug level monitoring.     

Prospective, randomized, double-blind comparison of metronidazole and tobramycin with clindamycin and tobramycin in the treatment of intra-abdominal sepsis.

In a prospective, double-blind study, clindamycin was compared with metronidazole, each combined with tobramycin and all by the intravenous route in the treatment of intra-abdominal sepsis. Twenty-three patients received clindamycin and 34 patients received 35 courses of metronidazole. Analysis of the clinical responses of patients indicates that the two antibiotic regiments are of equal efficacy in that there was no difference between them in terms of defervescence or duration of infection. Few adverse effects were noted, and all appeared to be of a minor nature.     

A randomized controlled trial comparing acetaminophen plus ibuprofen versus acetaminophen plus codeine plus caffeine after outpatient general surgery

BACKGROUND: Narcotics are used extensively in outpatient general surgery but are often poorly tolerated with variable efficacy. Acetaminophen combined with NSAIDs is a possible alternative. The objective of this study was to compare the efficacy of acetaminophen, codeine, and caffeine (Tylenol No. 3) with acetaminophen and ibuprofen for management of pain after outpatient general surgery procedures. STUDY DESIGN: A double-blind randomized controlled trial was performed in patients undergoing outpatient inguinal/umbilical/ventral hernia repair or laparoscopic cholecystectomy. Patients were randomized to receive acetaminophen plus codeine plus caffeine (Tylenol No. 3) or acetaminophen plus ibuprofen (AcIBU) 4 times daily for 7 days or until pain-free. Pain intensity, measured four times daily by visual analogue scale, was the primary outcome. Secondary end points included incidence of side effects, patient satisfaction, number of days until patient was pain-free, and use of alternative analgesia. RESULTS: One hundred forty-six patients were randomized (74 Tylenol No. 3 and 72 AcIBU), and 139 (95%) patients completed the study. No significant differences in mean or maximum daily visual analogue scale scores were identified between the 2 groups, except on postoperative day 2, when pain was improved in AcIBU patients (p = 0.025). During the entire week, mean visual analogue scale score was modestly lower in AcIBU patients (p = 0.018). More patients in the AcIBU group, compared with Tylenol No. 3, were satisfied with their analgesia (83% versus 64%, respectively; p = 0.02). There were more side effects with Tylenol No. 3 (57% versus 41%, p = 0.045), and the discontinuation rate was also higher in Tylenol No. 3-treated patients (11% versus 3%, p = 0.044). CONCLUSIONS: When compared with Tylenol No. 3, AcIBU was not an inferior analgesic and was associated with fewer side effects and higher patient satisfaction. AcIBU is an effective, low-cost, and safe alternative to codeine-based narcotic analgesia for outpatient general surgery procedures.     

A prospective randomised controlled trial of mezlocillin versus netilmicin in biliary surgery

A prospective randomised controlled trial of mezlocillin versus netilmicin in 133 patients undergoing biliary surgery at a district hospital is reported. Sixty-four patients received mezlocillin and 69 received netilmicin. The two groups of patients were comparable with regard to age, sex, underlying pathology and operative procedures performed. The incidence of infected bile at operation was 14.2% and both antibiotics were equally effective in reducing postoperative bacteraemia (0.75%) and wound infection (4.5%) to acceptable levels. It is concluded that netilmicin is a more cost-effective antibiotic in biliary surgery than mezlocillin.     

Open versus laparoscopic appendectomy. A prospective randomized comparison.

OBJECTIVE: The authors compare open and laparoscopic appendectomy in a randomized fashion with regard to length of operation, complications, hospital stay, and recovery time. METHODS: Adult patients (older than 14 years of age) with the diagnosis of acute appendicitis were randomized to either open or laparoscopic appendectomy over a 9-month period. All patients received preoperative antibiotics. The operative time was calculated as beginning with the incision and ending when the wound was fully closed. Patients that were converted from laparoscopic to open appendectomy were considered a separate group. Return to normal activity and work were determined by questioning during postoperative clinic, telephone, or mailed questionnaire. RESULTS: There was a total of 169 patients randomized, 88 to the open and 81 to the laparoscopic group. The groups were similar demographically. Of the 81 laparoscopic patients, 13 (16%) were converted to open. In the open group, 70 patients (79.5%) had acute appendicitis and 21 (23.9%) had perforative appendicitis. In the laparoscopic group, 62 patients (76.5%) had acute appendicitis and 10 (12.3%) had perforative appendicitis. There was no statistical difference in the return to activity or work between the laparoscopic and open groups. The operative time was significantly longer in the laparoscopic group (102.2 minutes vs. 81.7 minutes, p < 0.01). The hospital stay of 2.2 days in the laparoscopic group and 4.3 days in the open group was statistically (p = 0.007). There was no difference in the hospital stay for those with acute appendicitis (1.89 days vs. 2.61 days, p = 0.067) compared with those with a normal appendix but with pelvic inflammatory disease (1.1 days vs. 2.3 days, p = 0.11). There was a significant difference in patients with perforative appendicitis (1.5 days vs. 9.5 days, p < 0.01). The hospital cost for patients having laparoscopic appendectomy was $6077 and for an open appendectomy $7227 (p = 0.164). There were no increased complications associated with the laparoscopic technique. CONCLUSION: Laparoscopic appendectomy is comparable to open appendectomy with regard to complications, hospital stay, cost, return to activity, and return to work. There was a greater operative time involved with the laparoscopic technique. Laparoscopic appendectomy does not offer any significant benefit over the open approach for the routine patient with appendicitis.     

Prophylactic intra-abdominal drainage following colorectal anastomoses. A systematic review and meta-analysis of randomized controlled trials

BackgroundClinically evident Anastomotic Leakage (AL) remains one of the most feared complications after colorectal resections with primary anastomosis. The primary aim of this systematic review and meta-analysis was to determine whether Prophylactic Drainage (PD) after colorectal anastomoses confers any advantage in the prevention and management of AL.MethodsSystematic literature search was performed using MEDLINE, the Cochrane Central Register of Controlled Trials, and EMBASE databases for randomized studies comparing clinical outcomes of patients with Drained (D) or Undrained (UD) colorectal anastomoses performed for any cause.ResultsFour randomized controlled trials comparing D and UD patients undergoing colorectal resections with primary anastomosis were included for quantitative synthesis. In total, 1120 patients were allocated to group D (n = 566) or group UD (n = 554). The clinical AL rate was 8.5% in the D group and 7.6% in the UD group, with no statistically significant difference (P = 0.57). Rates of radiological AL (D: 4.2% versus UD: 5.6%; P = 0.42), mortality (D: 3.6% versus UD: 4.4%; P = 0.63), overall morbidity (D: 16.6% versus UD: 18.6%, P = 0.38), wound infection (D: 5.4% versus UD: 5.3%, P = 0.95), pelvic sepsis (D: 9.7% versus UD: 10.5%, P = 0.75), postoperative bowel obstruction (D: 9.9% versus UD: 6.9%, P = 0.07), and reintervention for abdominal complication (D: 9.1% versus UD: 7.9%, P = 0.48) were equivalent between the two groups.ConclusionsThe present meta-analysis of randomized controlled trials investigating the value of PD following colorectal anastomoses does not support the routine use of prophylactic drains.     

Results of a multicenter trial comparing imipenem/cilastatin to tobramycin/clindamycin for intra-abdominal infections.

We designed a multicenter study to compare tobramycin/clindamycin to imipenem/cilastatin for intra-abdominal infections. We included the Acute Physiology and Chronic Health Evaluation (APACHE II) index of severity and excluded patients without established infection. Two hundred ninety patients were enrolled, of whom 162 were evaluable. Using logistic regression to analyze both outcome at the abdominal site of infection and outcome as mortality, we found a significant correlation for both with APACHE II score (p less than 0.0001 for both). Next we analyzed the residual effect of treatment assignment and found a significant improvement in outcome for imipenem/cilastatin-treated patients (p = 0.043). The differences in outcome were explained by a higher failure rate for patients with gram-negative organisms for tobramycin/clindamycin-treated patients (p = 0.018). This was reflected in a significantly higher incidence of fasciitis requiring reoperation and prosthetic fascial replacement. Maximum peak tobramycin levels were analyzed for 63 tobramycin/clindamycin patients harboring gram-negative organisms. For failures the maximum peak was 6.4 +/- 1.9 micrograms/mL, and time to maximum peak was 4.6 +/- 5.2 days. For successes the maximum peak was 6.1 +/- 1.7 micrograms/mL, occurring at 3.8 +/- 2.6 days. This study supports inclusion of severity scoring in statistical analyses of outcome results and supports the notion that imipenem/cilastatin therapy improves outcome at the intra-abdominal site of infection as compared to a conventionally prescribed amino-glycoside-based regimen.     

Dexon plus versus Maxon fascial closure in morbid obesity: a prospective randomized comparison

A monofilament polyglyconate suture (Maxon) was developed as a longer-lasting suture associated with less potential for infection than braided polyglycolic acid suture (Dexon). The authors compared Dexon Plus and Maxon in a prospective randomized study of 84 consecutive morbidly obese patients who underwent vertical banded gastroplasty. Linea alba was closed with continuous running suture, reinforced with a few interrupted, sutures. After more than 2 years' follow-up, one seroma (2.4%), one wound infection (2.4%) and no hernias were found in the Dexon group. In contrast in the Maxon group there were three seromas (7.1%), four wound infections (9.5%) and four incisional hernias (9.5%, p less than 0.05). The hernias were noted between 2 and 10 1/2 months after the operation in two patients who had had wound infections and in two who had had seromas. When Maxon was used, the needle occasionally pulled off the suture and the ends beyond the knot projected rigidly. Dexon Plus was easier to handle in very fatty wounds.     

Cost-effectiveness study of imipenem/cilastatin versus meropenem in intra-abdominal infections

BACKGROUND: The efficacy of two carbapenems, imipenem/cilastatin (I/C, 1.5 g daily) versus meropenem (3 g daily) in intra-abdominal infections was assessed in a recent multicenter randomized clinical trial. The aim of this article is to perform a cost-effectiveness analysis as in real-world practice according to the findings of this clinical trial. METHODS: A decision tree was used to estimate the clinical outcomes and direct costs of treating intra-abdominal infections using the two carbapenems from the perspective of the Italian National Health Service (INHS) or a private insurance company (PIC). RESULTS: In a population of 30,000 patients with intra-abdominal infections in Italy, it was estimated that 97 potential deaths/year could be avoided if these patients were treated with I/C versus meropenem. In addition, from the perspective of INHS, the total costs of treatment were estimated as ITL 106,874 million and 134,042 million for I/C and meropenem, respectively. In favor of the PIC point of view, the total costs were estimated as ITL 110,500 million and 135,899 million for I/C and meropenem, respectively. CONCLUSION: The treatment of intra-abdominal infections with I/C is shown to be more effective (97 deaths avoided/year) and less costly than with meropenem (with a saving of ITL 27,168 and 25,399 million/year for INHS and PIC, respectively).     

Cardiovascular surgery prophylaxis. A randomized, controlled comparison of cefazolin and cefuroxime

A prospective double-blind trial was performed at a tertiary care center to evaluate perioperative cephalosporin prophylaxis in cardiac operations. Patients were randomized to receive either cefazolin (n = 104) or cefuroxime (n = 109), the preoperative dose being given within 1 hour before the initial incision. Drugs were continued for 48 hours (cefazolin, 1 gm intravenously every 8 hours; cefuroxime, 1.5 gm intravenously every 12 hours). Postoperative infections were assessed by trained nurse clinicians, and data were analyzed by the intention-to-treat principle. Sternal wound infections or mediastinitis occurred in one of 104 patients treated with cefazolin and 10 of 109 treated with cefuroxime (p = 0.01). Deep sternal wounds (including mediastinitis and sternal osteomyelitis) occurred in none of the cefazolin-treated patients and five cefuroxime-treated patients (p = 0.06). Although overall nosocomial infection rates were similar (16.3 versus 19.3 per 100), wound infection occurred somewhat more frequently with streptococci (groups B and D) in patients receiving cefazolin (four versus zero, p = 0.110); conversely staphylococcal infections were more frequent in the cefuroxime group (seven versus one, p = 0.066). Mean and median postoperative stay was 1 day shorter in the cefazolin group. In contrast to findings of a previous report, our data indicate that cefazolin prevented more sternal wound infections than cefuroxime, a finding that supports prophylaxis with a first-generation cephalosporin.