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Relaparotomy in peritonitis: prognosis and treatment of patients with persisting intraabdominal infection.

Some patients are prone to persisting intraabdominal infection regardless of initial eradication of the source of infection. Our aim was to characterize patients who had to undergo relaparotomy for persisting abdominal sepsis using simple clinical parameters and to define those patients who are susceptible to benefit of aggressive surgical treatment by early and repeated reoperations to control multiple organ dysfunction syndrome (MODS) caused by ongoing intraabdominal infection. Persisting abdominal sepsis was the cause of death in all of our patients who had to undergo relaparotomy. Controlling persisting abdominal sepsis should achieve a reduction in the tremendously high mortality rate. Performing a case-control study, we retrospectively reviewed 523 consecutive patients with secondary peritonitis treated from 1986 to 1996 and focused our attention on 105 patients, in whom standard surgical treatment of secondary peritonitis failed and who had to undergo relaparotomy for persisting abdominal sepsis (study group). Overall, there was no significant difference in the postoperative mortality rate between "planned relaparotomy" and "relaparotomy on demand" (54.5% versus 50. 6%). Equally clear risk estimations were given preoperatively by both the Acute Physiology and Chronic Health Evaluation (APACHE) II and the Goris scores. There was a significant difference between patients of the control group and patients of the study group with regard to preoperative APACHE II score, Goris score, age >70 years, albumin <30 g/L, extent of peritonitis, and outcome (p = 0.0001). Reexploration performed more than 48 hr after the initial operation resulted in a significantly higher mortality rate (76.5% versus 28%; p = 0.0001). However, the time of reoperation had no significant impact on survival in patients with an APACHE II score of > or = 26, because physiologic derangement is such that only a few patients could benefit from reoperation. The lowest mortality rate (9%) was achieved in patients who underwent reoperation on demand within 48 hr. We conclude that patients >70 years of age with secondary peritonitis extending over the entire abdomen and a greater degree of physiologic compromise (serum albumin levels <30 g/L, preoperative APACHE II scores >20, and existing organ failure measured by the Goris score) are at high risk for developing persistent intraabdominal infection. Our data show that timely relaparotomy provides the only surgical option that significantly improves outcome. However, aggressive surgical treatment has reached its limit in patients whose source of infection could not be controlled at the initial operation. To improve overall survival the decision to perform a relaparotomy on demand after an initially successful eradication of the source of infection must be made within 48 hr, at least before MODS emerges.

Abdomen↗

Effect of ciprofloxacin compared to gentamicin in the treatment of experimental intraabdominal infections in rats.

A reproducible experimental model of intraabdominal infections in rats has been developed in order to stimulate intraabdominal sepsis in patients. Preoperatively, the rats were fed with lean ground beef for two weeks in order to change the intestinal flora to one similar to that of humans. A 1-cm segment of ileum was isolated on its vascular pedicle. The intestine was then divided at each end of the segment and intestinal continuity was re-established by an end-to-end anastomosis. The segment of ileum was then returned to the abdominal cavity. This experimental model was used to compare the efficacy of ciprofloxacin alone and in combination with clindamycin with the combination gentamicin and clindamycin in the treatment of intraabdominal infections. Eighty per cent of the untreated animals died within four days. Within six days, 30% of the animals receiving ciprofloxacin died. Animals treated with ciprofloxacin plus clindamycin or gentamicin plus clindamycin had a significantly decreased mortality and increased cure rates during the experimental period. Only 5% of these animals died. Thus the combination of ciprofloxacin and clindamycin seems to be as successful as gentamicin plus ciprofloxacin in the treatment of intraabdominal infections.

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Monobactams and carbapenems for treatment of intraabdominal infections.

During the last decade improved clinical and microbiological methods have resulted in the realization that most intraabdominal infections involve both aerobic and anaerobic bacteria. Papers on the use of different antimicrobial agents directed against the polymicrobial flora of the infected site have been published. In this paper the use of monobactams and carbapenems for treatment of intraabdominal infections is reviewed. The review is based on data published since 1990. Three hundred forty-four patients participated in three trials where aztreonam combined with clindamycin was compared with other antimicrobial agents for treatment of intraabdominal infections. Eighty-six percent of the patients receiving aztreonam plus clindamycin were cured/improved, while 83% of the patients receiving the comparative drugs had favorable outcomes. Eleven trials compared imipenem/cilastatin versus other antimicrobial combinations for therapy of intraabdominal infections. One thousand three hundred seventy-five patients were evaluated in the trials. Eighty percent of patients treated with imipenem/cilastatin had favorable outcomes, while 81% of the patients receiving the comparative drugs were cured/improved. Nine studies including 1,205 patients for evaluation of meropenem versus other antimicrobial agents in the treatment of intraabdominal infections have been published. Cure/improvement was seen in 96% of the patients treated with meropenem and in 91% receiving the comparative drugs. One trial has been published comparing biapenem with imipenem/cilastatin for treatment of intraabdominal infections. Eighty-three patients participated, 65% of the patients in the biapenem group were cured/improved and 68% in the imipenem/cilastatin group.

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Intraabdominal infections: classification, mortality, scoring and pathophysiology.

Studies on intraabdominal infections have been difficult to compare in the past due to a missing system of classification for peritonitis. According to a recently developed classification system, secondary peritonitis, including spontaneous acute peritonitis, postoperative peritonitis and posttraumatic peritonitis, is the most common complication of severe intraabdominal infections. In several studies the mortality rate of postoperative peritonitis was still between 60% and 79%. Scoring systems were developed, some of them with the idea to predict mortality in peritonitis. Although the APACHE II score cannot predict the outcome of peritonitis in an individual patient, it is a reliable, valid and objective system for risk stratification in intraabdominal infections. Local trauma or bacterial contamination is responsible for an acute phase reaction, which involves the release of certain cytokines such as TNF-alpha, interleukin-1 (IL-1) and interleukin-6 (IL-6). The IL-6 seems to play an important role in the mechanism of the acute phase reaction, acting on hepatocytes to release acute phase proteins (e.g. CRP). Preliminary results of investigations of IL-6 levels in peritonitis indicate a possible role for IL-6 as a predictor of the outcome of peritonitis.

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Principles and limitations of operative management of intraabdominal infections.

Operative management of intraabdominal infections still rests on the principles of elimination of focus, reduction of contamination of the peritoneal cavity, and treatment of residual infection. To control the source of contamination from a perforated viscus primary closure, exclusion or resection may be considered with respect to the severity of peritonitis and to the underlying disease. The principle of "peritoneal toilet" with complementary use of systemic and/or local antibiotics is generally accepted even if the value of aggressive debridement is still debated controversely. For the treatment of residual and the prevention of recurrent infection, closed and open lavage techniques, the left-open abdomen, and planned relaparotomy represent the major approaches in severe generalized peritonitis when the infectious focus might not be securely controlled. The values and disadvantages of different regimens are discussed, additional measures are briefly described, and an outlook on areas of further research is given.

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Operative and nonoperative therapy of intraabdominal infections.

The basic principles for treating intraabdominal infections are fourfold: (1) to obliterate the infectious source; (2) to purge bacteria and toxins; (3) to maintain organ system function and (4) to tame the inflammatory process. Operative and nonoperative treatment options are available. Operative therapy includes different strategies: (1) the standard operation; (2) advanced procedures to decompress the abdominal compartment syndrome and (3) percutaneous drainage of abscesses. Nonoperative management includes: (1) antibiotic therapy; (2) hemodynamic and pulmonary support; (3) nutrition and metabolic support; (4) detoxification support (including support of renal and hepatic function) and (5) inflammation modulating therapy. Standard operative management addresses the first two principles and has been shown to reduce mortality by more than 50%. A recent extensive series of studies reports mortality rates around 20%. Patients with an abdominal compartment syndrome (intraabdominal pressure over 25 torr) and patients with advanced disease and compounding risk factors best documented by high APACHE-II scores are candidates for more advanced operations. The mortality rate following abdominostomy (leaving the abdomen open) in 869 patients participating in 37 studies was 42%, when the abdomen was simply left open for decompression (open abdominostomy). When a mesh was used to cover the abdominal wound (mesh abdominostomy) 39% of 439 patients enrolled in 12 studies died. Patients who underwent staged abdominal repair (STAR abdominostomy) faired better. Of 385 patients in 11 studies 28% died. Data from antibiotic studies as well as from immunomodulating therapy are nonconclusive at this point with respect to reducing mortality in intraabdominal infection.

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Prospective randomized trials affect the outcomes of intraabdominal infection.

OBJECTIVE: To compare the characteristics and outcomes of patients with intraabdominal infections enrolled in prospective randomized trials (PRTs) with those of a cohort of patients not enrolled in a trial. SUMMARY BACKGROUND DATA: Prospective randomized trials are the gold standard for the evaluation of new treatments. Patients are screened using rigorous eligibility criteria and sometimes are excluded from PRTs because of associated medical conditions or more severe illness. However, the effect that the exclusion of these patients has on the applicability of clinical trial outcomes has not been defined. METHODS: One hundred sixty-eight adults with intraabdominal infection were treated at a single institution during 7 years. Fifty-three patients were enrolled in four PRTs comparing various antibiotic regimens for treatment; 115 were not enrolled. Patient characteristics and outcomes of these two groups were compared. RESULTS: Patients with infections from appendicitis (n = 68) had a low severity of illness and similar outcomes in both groups. These patients and those for whom a concurrent PRT was unavailable were excluded from subsequent analysis. Eighty-eight patients (42 PRT, 46 not enrolled) with serious infection remained for analysis. Patients enrolled in PRTs were younger, had less severe illness, had a decreased length of stay, a lower incidence of antibiotic resistance, and less frequent extraabdominal infections than those not enrolled in a trial. Patients enrolled in PRTs were more likely to be cured and were less likely to die. Logistic regression analysis demonstrated that cure was associated with a lower initial severity of illness, absence of antibiotic resistance, and participation in a PRT. CONCLUSIONS: Patients with intraabdominal infection enrolled in PRTs have an increased likelihood of cure and survival. This is due in part to a lower incidence of antibiotic resistance, which may reflect improved drug selection. Patients not enrolled in PRTs are at greater risk for treatment failure and death because of concomitant illness. Outcomes from PRTs may not be applicable to all patients with intraabdominal infections.

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Nosocomial infections adversely affect the outcomes of patients with serious intraabdominal infections.

BACKGROUND: Patients with serious intraabdominal infections (IAI) who subsequently acquire nosocomial infections (NI) have been shown to have adverse outcomes. We evaluated factors that put patients at risk for developing NI and examined the effect of the NI on outcomes. METHODS: This study was a retrospective review of NI among 168 patients diagnosed with IAI over a seven-year period. RESULTS: Sixty-six patients (39.3%) developed 98 NI (23 urinary tract, 20 surgical site, 19 pneumonia, 14 bloodstream, 12 recurrent peritonitis, seven intravascular catheter-related, and three enteric). There were 35 males and 31 females. Patients with NI were older (56.0 +/- 18.3 vs. 47.0 +/- 15.6 years, p = 0.001), had a higher admission APACHE II score (10.7 +/- 6.1 vs. 7.5 +/- 5.1 points, p = 0.001), and more often had concomitant medical diagnoses (27.3% vs. 12.7%, OR = 2.57, 95% CI: 1.159-5.69, p = 0.018) than those who did not develop infection. Antimicrobial resistance among the IAI was higher in the NI group (19.7 vs. 5.9%, OR = 3.93, 95% CI: 1.41-10.93, p = 0.006). Patients who developed NI had an increased mortality rate (27.0% vs. 4.0%, OR = 8.87, 95% CI: 2.82-27.86, p < or = 0.0001), longer hospital stay (24.7 +/- 19.5 vs. 11.7 +/- 8.1 days, p < or = 0.0001), required more days of intravenous antibiotics (11.5 +/- 8.0 vs. 7.6 +/- 4.4 days, p < or = 0.0001), and were more likely to be admitted to an intensive care unit (54.5% vs. 25.5%, OR = 3.51, 95% CI: 1.82-6.77, p < or = 0.0001). Multivariate analysis demonstrated that antimicrobial resistance and an APACHE II score of > or = 10 independently predicted the development of a nosocomial infection. Age >/= 50 years, APACHE II score > or = 10, or the presence of a NI independently predicted death. CONCLUSIONS: The development of NI following treatment of an IAI significantly affects mortality, hospital length of stay, and treatment. Early recognition and treatment of these infections, combined with strategies to prevent NI, may be important to improve outcomes in this patient population.

Adult↗

Definition of the role of enterococcus in intraabdominal infection: analysis of a prospective randomized trial.

BACKGROUND: The role of enterococcus in intraabdominal infection is controversial. This study examines the contribution of enterococcus to adverse outcome in a large intraabdominal infection trial. METHODS: A randomized prospective double-blind trial was performed to compare two different antimicrobial regimens in combination with surgical or percutaneous drainage in the treatment of complicated intraabdominal infections. A total of 330 valid patients was enrolled from 22 centers in North America. RESULTS: In 330 valid patients, 71 had enterococcus isolated from the initial drainage of an intraabdominal focus of infection. This finding was associated with a significantly higher treatment failure rate than that of patients without enterococcus (28% versus 14%, p < 0.01). In addition, only Acute Physiology and Chronic Health Evaluation II score and presence of enterococcus were significant independent predictors of treatment failure when stepwise logistic regression was performed (p < 0.01 and < 0.03). Risk factors for the presence of enterococcus include age, Acute Physiology and Chronic Health Evaluation II, preinfection hospital length of stay, postoperative infections, and anatomic source of infection. There was no difference between the clinical trial treatment regimens with regard to overall failure, failure associated with enterococcus, or frequency of enterococcal isolation. CONCLUSIONS: This study is the first to report enterococcus as a predictor of treatment failure in complicated intraabdominal infections. This trial also identifies several significant risk factors for the presence of enterococcus in such infections.

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Antimicrobial therapy for intraabdominal infection.

Timely and appropriate antimicrobial therapy is an essential component of the management of intraabdominal infection. Over the past three decades, our ability to treat these infections optimally has been enhanced by an increased understanding of the underlying microbial pathogens, by the development of new antimicrobial agents, and by the completion of several well-controlled clinical trials that guide treatment. This article provides an overview of the approach to antimicrobial therapy in patients with intraabdominal infection. A literature review was performed to collect the information used in this article. Data were derived from experimental and clinical studies evaluating the microbiology and treatment of intraabdominal infections. Evidence from both animal studies and clinical trials supports the initiation of empiric antimicrobial therapy directed against Escherichia coli and other common members of the family Enterobacteriaceae, as well as the anaerobe Bacteroides fragilis. Based on this premise, the clinician is faced with a broad selection of possible single agents, as well as combinations of agents that fulfill these criteria. The factors involved in selecting a specific regimen include consideration of the antimicrobial spectrum of various agents, experimental animal studies evaluating their efficacy, and, importantly, efficacy in well-designed clinical trials. In addition, consideration of safety profiles, pharmacokinetics, and cost of specific pharmaceutical agents should be made when selecting a regimen. Antimicrobial therapy is an important component of the management of intraabdominal infection. The results of well-designed clinical trials evaluating various aspects of therapy should serve to guide treatment.

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Intraabdominal infections in infants and children: descriptions and definitions.

OBJECTIVE: To define intraabdominal infections in infants and children. DESIGN: Summary of the literature with review and consensus by experts in the field. RESULTS: Intraabdominal infections are common in infants and children and comprise a broad range of disorders of greatly variable severity. In addition to microbiologically mediated processes, other inflammatory disorders frequently present similar clinical syndromes. More aggressive and effective therapy for prematurity, chronic diseases of childhood, malignancies, immunodeficiencies, and organ failure, including transplantation, is likely to increase the frequency with which some of these infections are encountered. Only a limited number of processes have been clearly defined in the pediatric literature. CONCLUSIONS: Criteria defining intraabdominal infection are proposed based on reports in the pediatric literature and expert opinion. Additional study of individual disorders, diagnostic criteria, and approach to management is warranted.

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Aztreonam plus clindamycin vs. tobramycin plus clindamycin for the treatment of intraabdominal infections.

Sixty-six patients with acute intraabdominal infections due to gram-negative aerobic organisms were treated with aztreonam plus clindamycin or with tobramycin plus clindamycin in a multicenter, comparative, randomized study. The patients had undergone a variety of surgical procedures; most of them had peritonitis. Thirty-three of the 36 patients in the aztreonam group and 26 of the 30 patients in the tobramycin group had satisfactory clinical responses. Only one gram-negative aerobic pathogen, a strain of Pseudomonas aeruginosa, persisted after treatment; the patient involved was in the tobramycin group. The incidences of adverse reactions, superinfections, and abnormal laboratory values were low in each treatment group. The difference between the efficacies of the two regimens was not statistically significant. This study suggests that aztreonam may be a useful alternative to the aminoglycosides in the treatment of gram-negative intraabdominal infections.

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[Clinical efficacy of cefmetazole in intraabdominal infection].

A number of different organisms can be isolated from intraabdominal infection. The most common are aerobic Gram-negative bacilli. Anaerobes are not unusual. From June 1989 to January 1990, Cefmetazole was administered to 23 patients with intraabdominal infection at Veterans General Hospital-Taipei. There were six patients with spontaneous bacterial peritonitis, five biliary tract infection, five liver abscesses, five with pelvic inflammatory disease, one acute ruptured appendicitis and another intraabdominal abscess. In addition, ten patients had sepsis. Clinical response was satisfactory in 21 (91.3%) of 23 patients, and the microbiological eradication rate was 90% (36/40). One patient with Streptococcus and Bacteroides oralis liver abscess relapsed after organism eradication. Therapy failed in a case with Pseudomonas aeruginosa and Bacteroides fragilis infection. This study showed Cefmetazole to be an effective and safe antibiotic for treatment of intraabdominal infection.

Adolescent↗

Effects of pneumoperitoneum created through CO2 insufflation and parameters of mechanical ventilation (PEEP application) on systemic dissemination of intraabdominal infections.

BACKGROUND: To examine whether CO2 pneumoperitoneum and positive end expiratory pressure (PEEP) in mechanical ventilation affect the systemic spread of intraabdominal infection. METHODS: Sprague-Dawley male rats weighing 200-300 g were allocated to three groups of 12 animals in each. All rats received mechanical ventilation under general anesthesia. An intraabdominal infection model was established by injecting with 1 ml of Escherichia coli (10(9) CFU/mL) intraperitoneally. Half of the animals in each group were exposed to PEEP (10 cmH2O). CO2 pneumoperitoneum at 13 mmHg was applied to the rats in group 1. Group 2 rats underwent laparotomy. Group 3 served as controls. In addition, TNF-alpha serum levels were measured at baseline and 3 h. A peritoneal specimen for histopathological examination were obtained after the rats were killed at the end of 3 h. For the assessment of data, descriptive statistical methods (mean, standard deviation) as well as Friedman test for repeated measurements in multiple groups, Kruskal-Wallis test for intergroup comparisons, Dunn's multiple comparison test for subgroup comparisons, Mann-Whitney U test for comparisons between paired groups, chi-square and Fisher's exact test for comparison of qualitative data, and McNemar's test for assessment of changes in group variables over time were used. The results were considered statistically significant if probability (p) values were <0.05. RESULTS: Grades of peritonitis in group 1 and 2 were seen to differ nonsignificantly. In group 1, baseline blood cultures were not included in the assessment between the subgroups that received PEEP or not, as there was no growth in any of the subgroups. No significant difference was detected between growth in blood cultures at 1, 2, and 3 h ( p > 0.05). Application of PEEP in subgroups did not alter the blood culture results ( p > 0.05). Significant differences were seen between the initial and final TNF-alpha values of groups (KW: 18.94, p < 0.0001). The values in control group were observed to be significantly lower than those in groups 1 and 2 ( p < 0.01, p < 0.001). Bacteremia and systemic spread of the intraabdominal infection did appear to be different according to the PEEP application. After the assessments of ventilation parameters in our study, significant reductions in pH and HCO3 levels were detected in group 1 as a result of pneumoperitoneum, which was consistent with the literature. There is a significant difference between pH values at baseline and at the end of 1 h because of pneumoperitoneum (Fr: 10.01, p < 0.05). PEEP application in subgroups did not create significant differences in terms of respiratory parameters ( p < 0.01). CONCLUSION: No difference was found between the applications of CO2 pneumoperitoneum and laparotomy with regard to bacteremia and infection-induced peritonitis. It was determined that pneumoperitoneum along with PEEP application had neither a positive nor a negative impact on intraabdominal infection.

Animals↗

Comparison of intravenous/oral ciprofloxacin plus metronidazole versus piperacillin/tazobactam in the treatment of complicated intraabdominal infections.

OBJECTIVE: To compare the safety and efficacy of intravenous (IV) ciprofloxacin plus IV metronidazole (CIP+MET) with that of IV piperacillin/tazobactam (PIP/TAZO) in adults with complicated intraabdominal infections, and to compare the efficacy of sequential IV-to-oral CIP+MET therapy with that of the IV CIP-only regimen. SUMMARY BACKGROUND DATA: Treatment of intraabdominal infections remains a challenge, mainly because of their polymicrobial etiology and attendant death and complications. Antimicrobial regimens using sequential IV-to-oral therapy may reduce the length of hospital stay. METHODS: In this multicenter, randomized, double-blind trial involving 459 patients, clinically improved IV-treated patients were switched to oral therapy after 48 hours. Overall clinical response was the primary efficacy measurement. RESULTS: A total of 282 patients (151 CIP+MET, 131 PIP/TAZO) were valid for efficacy. Of these patients, 64% CIP+MET and 57% PIP/TAZO patients were considered candidates for oral therapy. Patients had a mean APACHE II score of 9.6. The most common diagnoses were appendicitis (33%), other intraabdominal infection (29%), and abscess (25%). Overall clinical resolution rates were statistically superior for CIP+MET (74%) compared with PIP/TAZO (63%). Corresponding rates in the subgroup suitable for oral therapy were 85% for CIP+MET and 70% for PIP/TAZO. Postsurgical wound infection rates were significantly lower in CIP+MET (11%) versus PIP/TAZO patients (19%). Mean length of stay was 14 days for CIP+MET and 17 days for PIP/TAZO patients. CONCLUSION: CIP+MET, initially administered IV and followed by CIP+MET oral therapy, was clinically more effective than IV PIP/TAZO for the treatment of patients with complicated intraabdominal infections.

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Ertapenem versus piperacillin/tazobactam in the treatment of complicated intraabdominal infections: results of a double-blind, randomized comparative phase III trial.

OBJECTIVE: To examine the clinical efficacy and safety of ertapenem, a novel beta-lactam agent with wide activity against common pathogens encountered in intraabdominal infection. SUMMARY BACKGROUND DATA: Ertapenem has a pharmacokinetic profile and antimicrobial spectrum that support the potential for use as a once-a-day agent for the treatment of common mixed aerobic and anaerobic infections. METHODS This prospective, randomized, controlled, and double-blind trial was conducted to compare the safety and efficacy of ertapenem with piperacillin/tazobactam as therapy following adequate surgical management of complicated intraabdominal infections. RESULTS: Six hundred thirty-three patients were included in the modified intent-to-treat population, with 396 meeting all criteria for the evaluable population. Patients with a wide range of infections were enrolled; perforated or abscessed appendicitis was most common (approximately 60% in microbiologically evaluable population). A prospective, expert panel review was conducted to assess the adequacy of surgical source control in patients who were failures as a component of evaluability. For the modified intent-to-treat groups, 245 of 311 patients treated with ertapenem (79.3%) were cured, as were 232 of 304 (76.2) treated with piperacillin/tazobactam. One hundred seventy-six of 203 microbiologically evaluable patients treated with ertapenem (86.7%) were cured, as were 157 of the 193 (81.2%) treated with piperacillin/tazobactam. CONCLUSIONS: In this study, the efficacy of ertapenem 1 g once a day was equivalent to piperacillin/tazobactam 3.375 g every 6 hours in the treatment of a range of intraabdominal infections. Ertapenem was generally well tolerated and had a similar safety and tolerability profile to piperacillin/tazobactam. A formal process for review of adequacy of source control was found to be of benefit. The results of this trial suggest that ertapenem may be a useful option that could eliminate the need for combination and/or multidosed antibiotic regimens for the empiric treatment of intraabdominal infections.

Abdominal Abscess↗

Results of a clinical trial of clinafloxacin versus imipenem/cilastatin for intraabdominal infections.

OBJECTIVE: Clinafloxacin is a novel quinolone with wide activity against the plethora of microorganisms encountered in intraabdominal infections. This trial was performed to examine its clinical efficacy. SUMMARY BACKGROUND DATA: Clinafloxacin is representative of a new class of quinolones with considerable antimicrobial activity resulting from their mechanisms of action and pharmacodynamics. There is, however, concern about specific potential toxicities, including photosensitivity. METHODS: This prospective, randomized, double-blind trial was conducted to compare clinafloxacin with imipenem/cilastatin as adjuncts in the management of complicated intraabdominal infections. RESULTS: Five hundred twenty-nine patients were included in the intent-to-treat population, with 312 meeting all criteria for the valid population. Patients with a wide range of infections were enrolled; perforated or abscessed appendicitis was the most common (approximately 50%). One hundred twenty-three of the 150 valid patients treated with clinafloxacin (82%) had successful outcomes, as did 130 of the 162 (80%) treated with imipenem. For the intent-to-treat groups, 219 of 259 patients treated with clinafloxacin (85%) had successful outcomes, as did 219 of 270 patients treated with imipenem/cilastatin (81%). Treatment failure occurred in 39 patients who underwent drainage. There were substantially more gram-negative organisms recovered from the patients with treatment failure who were initially treated with imipenem/cilastatin. CONCLUSIONS: The results of this study clearly demonstrate the safety and efficacy of clinafloxacin in the treatment of a range of intraabdominal infections, and in patients with a broad range of physiologic disturbances.

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Proposed definitions for diagnosis, severity scoring, stratification, and outcome for trials on intraabdominal infection. Joint Working Party of SIS North America and Europe.

Analysis of the experience with scientific studies on patients with secondary intraabdominal infection has revealed that problems of interpretation and comparability between studies exist as they relate to variable diagnostic criteria, unmeasured severity of disease, and unclear outcome measures. A consistent system of definitions has been developed to address these deficiencies. Intraabdominal infection is defined as clinical peritonitis requiring both operative and microbiological confirmation for proof of infection. The APACHE II system is proposed for grading the severity of the infection and for stratification of patient risk of mortality. Mortality and time until death, on one hand, and recovery and time until recovery, on the other, are proposed as the main outcome measures, both being independently and positively defined. It is anticipated that this system of minimum rules will produce studies that can be compared, hence, accelerating knowledge and understanding about intraabdominal infection and its best treatment.

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