Centers for disease control and prevention guideline for the prevention of surgical site infection, 2017

IMPORTANCE: The human and financial costs of treating surgical site infections (SSIs) are increasing. The number of surgical procedures performed in the United States continues to rise, and surgical patients are initially seen with increasingly complex comorbidities. It is estimated that approximately half of SSIs are deemed preventable using evidence-based strategies. OBJECTIVE: To provide new and updated evidence-based recommendations for the prevention of SSI. EVIDENCE REVIEW: A targeted systematic review of the literature was conducted in MEDLINE, EMBASE, CINAHL, and the Cochrane Library from 1998 through April 2014. A modified Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach was used to assess the quality of evidence and the strength of the resulting recommendation and to provide explicit links between them. Of 5759 titles and abstracts screened, 896 underwent full-text review by 2 independent reviewers. After exclusions, 170 studies were extracted into evidence tables, appraised, and synthesized. FINDINGS: Before surgery, patients should shower or bathe (full body) with soap (antimicrobial or nonantimicrobial) or an antiseptic agent on at least the night before the operative day. Antimicrobial prophylaxis should be administered only when indicated based on published clinical practice guidelines and timed such that a bactericidal concentration of the agents is established in the serum and tissues when the incision is made. In cesarean section procedures, antimicrobial prophylaxis should be administered before skin incision. Skin preparation in the operating room should be performed using an alcohol-based agent unless contraindicated. For clean and clean-contaminated procedures, additional prophylactic antimicrobial agent doses should not be administered after the surgical incision is closed in the operating room, even in the presence of a drain. Topical antimicrobial agents should not be applied to the surgical incision. During surgery, glycemic control should be implemented using blood glucose target levels less than 200 mg/dL, and normothermia should be maintained in all patients. Increased fraction of inspired oxygen should be administered during surgery and after extubation in the immediate postoperative period for patients with normal pulmonary function undergoing general anesthesia with endotracheal intubation. Transfusion of blood products should not be withheld from surgical patients as a means to prevent SSI. CONCLUSIONS AND RELEVANCE: This guideline is intended to provide new and updated evidence-based recommendations for the prevention of SSI and should be incorporated into comprehensive surgical quality improvement programs to improve patient safety.

Meta-analysis and trial sequential analysis of triclosan-coated sutures for the prevention of surgical-site infection.

BACKGROUND: Triclosan-coated sutures (TCS) were developed to reduce the risk of surgical-site infection (SSI). Level 1A evidence of effectiveness has been presented in various recent meta-analyses, yet well designed RCTs have not been able to reproduce these favourable results. The aim of this study was to evaluate all available evidence critically with comprehensive analysis to seek a more reliable answer regarding the effectiveness of TCS in the prevention of SSI. METHODS: PubMed, MEDLINE, Embase and Cochrane Library databases were searched from 1990 to November 2015 for RCTs that compared TCS with sutures that were exactly the same, but uncoated, in the prevention of SSI. Pooled relative risks (RRs) with corresponding 95 per cent confidence intervals were estimated using a random-effects model. Metaregression was used to substantiate subgroup effects, trial sequential analysis was employed to assess the risk of random error, and quality of evidence was determined using Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. RESULTS: Twenty-one RCTs including 6462 patients were included. Risk of bias was serious. Pooled effects showed a RR of 0·72 (95 per cent c.i. 0·60 to 0·86; P < 0·001) for all publications. At a risk of 138 SSIs per 1000 procedures, the use of TCS reduced this by 39 (95 per cent c.i. 19, 55). Trial sequential analysis confirmed a RR reduction of 15 per cent for the use of TCS. CONCLUSION: GRADE assessment shows moderate-quality evidence that TCS are effective in reducing SSI. Trial sequential analysis indicates that the effect was robust, and additional data are unlikely to alter the summary effect.

Meta-analysis of lower perioperative blood glucose target levels for reduction of surgical-site infection.

BACKGROUND: There is a clear association between hyperglycaemia and surgical-site infection (SSI). Intensive glucose control may involve a risk of hypoglycaemia, which in turn results in potentially severe complications. A systematic review was undertaken of studies comparing intensive versus conventional glucose control protocols in relation to reduction of SSI and other outcomes, including hypoglycaemia, mortality and stroke. METHODS: PubMed, Embase, CENTRAL, CINAHL and WHO databases from 1 January 1990 to 1 August 2015 were searched. Inclusion criteria were RCTs comparing intensive with conventional glucose control protocols, and reporting on the incidence of SSI. Meta-analyses were performed with a random-effects model, and meta-regression was subsequently undertaken. Targeted blood glucose levels, achieved blood glucose levels, and important adverse events were summarized. RESULTS: Fifteen RCTs were included. The summary estimate showed a significant benefit for an intensive compared with a conventional glucose control protocol in reducing SSI (odds ratio (OR) 0·43, 95 per cent c.i. 0·29 to 0·64; P < 0·001). A significantly higher risk of hypoglycaemic events was found for the intensive group compared with the conventional group (OR 5·55, 2·58 to 11·96), with no increased risk of death (OR 0·74, 0·45 to 1·23) or stroke (OR 1·37, 0·26 to 7·20). These results were consistent both in patients with and those without diabetes, and in studies with moderately strict and very strict glucose control. CONCLUSION: Stricter and lower blood glucose target levels of less than 150 mg/dl (8·3 mmol/l), using an intensive protocol in the perioperative period, reduce SSI with an inherent risk of hypoglycaemic events but without a significant increase in serious adverse events.

Mechanisms of human neutrophil oxidant production after severe injury.

BACKGROUND: The purpose of this study was to determine the mechanisms of enhanced oxidant production after severe injury. METHODS: Neutrophils were harvested from patients within 24 hours of admission who had an injury severity score greater than 16. Nonadherent and adherent neutrophil oxidant production was measured after N-formyl-methionyl-leucyl-phenylalanine (fMLP) stimulation. Translocation of cytochrome b558 and cytosolic components p47phox and p67phox were determined by oxidation-reduction spectroscopy and immunoblotting, respectively. Flow cytometry measured integrin expression. Integrin and p47phox colocalization was examined by confocal microscopy. RESULTS: Eighteen patients were studied within 15 +/- 1.4 hours. Four women and 14 men suffered a blunt injury and had a mean injury severity score of 22 (range, 16 to 34). Nonadherent patient neutrophils showed a decrease in fMLP-stimulated oxidant production, whereas adherent neutrophil oxidant production was increased in both the vehicle control and fMLP-stimulated groups. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase components p47phox and cytochrome b558 were mobilized to the plasma membrane, whereas p67phox showed minimal change. Integrin CD11b a chain showed a significant increase in expression. Confocal microscopy showed colocalization of p47phox and a chain CD11b on the plasma membrane of patient neutrophils. CONCLUSIONS: Colocalization of NADPH oxidase components and integrins may regulate the enhanced oxidant production in human neutrophils after severe injury.

Granulocyte-colony stimulating factor in the prevention of postoperative infectious complications and sub-optimal recovery from operation in patients with colorectal cancer and increased preoperative risk (ASA 3 and 4). Protocol of a controlled clinical trial developed by consensus of an international study group. Part one: rationale and hypothesis.

GENERAL DESIGN: Presentation of a novel study protocol to evalue the effectiveness of an immune modifier (rhG-CSF, filgrastim): prevention of postoperative infectious complications and sub-optimal recovery from operation in patients with colorectal cancer and increased preoperative risk (ASA 3 and 4). The rationale and hypothesis are presented in this part of the protocol of the randomised, placebo controlled, double-blinded, single-centre study performed at an university hospital (n = 40 patients for each group). OBJECTIVE: Part one of this protocol describes the concepts of three major sections of the study: Definition of optimum and sub-optimal recovery after operation. Recovery, as an outcome, is not a simple univariate endpoint, but a complex construction of mechanistic variables (i. e. death, complications and health status assessed by the surgeon), quality of life expressed by the patient, and finally a weighted outcome judgement by both the patient and the surgeon (true endpoint). Its conventional early assessment within 14-28 days is artificial: longer periods (such as 6 months) are needed for the patient to state: "I am now as well as I was before". Identification of suitable target patients: the use of biological response modifiers (immune modulators) in addition to traditional prophylaxes (i. e. antibiotics, heparin, volume substitutes) may improve postoperative outcome in appropriate selected patients with reduced host defence and increased immunological stress response, but these have to be defined. Patients classified as ASA 3 and 4 (American Society for Anaesthesiologists) and with colorectal cancer will be studied to prove this hypothesis. Choice of biological response modifier: Filgrastim has been chosen as an example of a biological response modifier because it was effective in a new study type, clinic-modelling randomised trials in rodents, and has shown promise in some clinical trials for indications other than preoperative prophylaxis. It has also enhanced host defence and has been anti-inflammatory in basic research. CONCLUSION: The following hypothesis will be tested in patients with operations for colorectal cancer and increased preoperative risk (ASA 3 and 4): is the outcome as evaluated by the hermeneutic endpoint (quality of life expressed by the patient) and mechanistic endpoints (mortality rate, complication rate, relative hospital stay, assessed by the doctor) improved in the group receiving filgrastim prophylaxis in comparison with the placebo group? Quality of life will be the first primary endpoint in the hierarchical, statistical testing of confirmatory analysis.

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.

Chemokine regulation of neutrophil function in surgical inflammation.

BACKGROUND: Morbidity and even mortality correlate closely with major injury that causes a systemic inflammatory response. Cytokines and bioactive molecules present at the inflammatory site induce this response and regulate neutrophil proinflammatory responses. The CXC chemokines, important for neutrophil recruitment and activation, include interleukin 8 (IL-8), granulocyte chemotactic protein 2 (GCP-2), and epithelial cell-derived neutrophil attractant 78 (ENA-78). They induce neutrophil responses via 2 cell-surface receptors, CXCR-1 and CXCR-2. All 3 chemokines bind CXCR-2 with high affinity. Only IL-8 and GCP-2 bind CXCR-1 with high affinity. HYPOTHESIS: The CXC chemokines regulate neutrophil responses differently. METHODS: Pretreatment of neutrophils from healthy volunteers with IL-8, GCP-2, or ENA-78; measured IL-8-induced migration; and tumor necrosis factor alpha (TNF-alpha)-induced peroxide production. RESULTS: Flow cytometry and radioligand binding data indicate that IL-8, GCP-2, and ENA-78 equivalently reduced CXCR-1 and CXCR-2 cell surface expression by 34% to 54%. All treatments decreased affinity of both receptors 1.5- to 2-fold. However, only IL-8 pretreatment inhibited chemotaxis to 10-nmol/L IL-8 (mean +/- SE inhibition, 62%+/-6%). Although IL-8 and GCP-2, but not ENA-78, suppressed TNF-alpha-induced oxidant production (mean +/- SE inhibition, 42%+/-8% and 40%+/-23%, respectively), only GCP-2 inhibited the oxidative response to complement fragment C5a, and to the bacterial cell wall peptide N-formyl-methionyl-leucyl-phenylalanine. CONCLUSIONS: The CXC chemokines regulate neutrophil proinflammatory functions differently. A thorough understanding of mechanisms for modulating neutrophil responses in inflammation will aid the development of interventions that reduce morbidity and mortality associated with severe trauma and sepsis.

Preferential loss of CXCR-2 receptor expression and function in patients who have undergone trauma.

BACKGROUND: In response to traumatic injury or infection, human neutrophils are directed to the site of injury or infection by CXC chemokines that signal via 2 receptors, CXCR-1 and CXCR-2. In vitro studies have shown preferential loss of CXCR-2 expression and function after exposure to interleukin 8, N-formyl-methionyl-leucyl-phenylalanine (fMLP), C5a, and tumor necrosis factor alpha. HYPOTHESIS: CXCR-2 expression and function are preferentially down-regulated in severely injured patients. METHODS: We studied 20 patients within 24 hours of admission to the hospital. Patients with head injuries were excluded. Injury Severity Scores (range, 1-50; mean, 35) were calculated for each patient. To determine expression of CXCR-1 and CXCR-2, flow cytometry was used. Intracellular calcium mobilization and neutrophil migration to 10 nmol of interleukin 8, growth-related oncogene alpha, and fMLP was measured to determine receptor function. RESULTS: Compared with CXCR-1, there is a greater loss of CXCR-2 receptor expression in the severely injured group (P = .01). Neutrophils from patients with Injury Severity Scores greater than 16 did not mobilize calcium in response to growth-related oncogene alpha. However, there was no loss of calcium mobilization to interleukin 8 or fMLP. Chemotaxis to various stimulants is decreased in all injury groups. CONCLUSIONS: CXCR-2 expression and function are preferentially down-regulated in severely injured patients. Our data suggest that there are multiple mechanisms, in addition to receptor down-regulation, that play a role in the loss of migration and calcium flux in human neutrophils after injury.

Tumor necrosis factor alpha regulates CXC chemokine receptor expression and function.

The alpha chemokine family is central to the participation of neutrophils in the acute inflammatory response. These substances interact with neutrophils through two cell surface receptors, CXCR-1 and CXCR-2 (formally known as IL-8R-1 and IL-8R-2). We investigated the possible regulatory effects of tumor necrosis factor alpha (TNFalpha) pretreatment on CXCR-1 and CXCR-2. To this end, we examined these receptors with flow cytometry, radioligand binding, Northern blot analyzes, calcium mobilization, and chemotaxis experiments on human neutrophils. In flow cytometry experiments, TNFalpha pretreatment substantially decreased cell surface CXCR-2 receptor levels but showed partial recovery at 120 min. On the other hand, CXCR-1 receptor levels had a sharp decline at 15 min and maintained that level to 120 min. Northern blot analyzes showed that mRNA levels of both IL-8 receptors were essentially unchanged after 45 min of TNFalpha pretreatment, but declined markedly following 2 h of pretreatment. Chemotaxis experiments on cells treated with TNFalpha for 5-120 min showed a substantial down-regulation of chemotaxis to IL-8 and GROalpha. This was noted to be much greater than the decline in cell surface receptors. Calcium mobilization experiments revealed minimal inhibition of the IL-8-induced increase in calcium after pretreatment with TNFalpha, but the response to NAP-2 was substantially inhibited. The data demonstrate differential regulation of the IL-8 receptor.

Second step: testing-outcome measurements.

Despite worldwide enthusiasm for endoscopic surgery, this new technology is now on the top of McKinlay's "product life circle curve." Critical questions are being asked about its benefits and burdens, but the concepts applied and the methodologies used for technology assessment are in a similar position as endoscopic surgery and need a critical evaluation. (1) There are incorrect and outdated concepts for the scientific basis of surgery (surgical theory) including the basic sciences involved; biomedicine still dominates, but assessment of outcome after operations is no longer possible without clinical epidemiology and social psychology. (2) Based on an outdated scientific theory for surgery, an outdated concept of disease is still propagated. It is denoted as mechanical and is based solely on biomedicine. Human subjects are reduced to biologic machines, and outcomes measurement excludes most dimensions of functioning and well-being. To achieve a valid result for outcome measures, a hermeneutic approach must be combined with the mechanical approach. (3) Based on an outdated model of disease, the outcomes used in endoscopic surgery rely too much on traditional measures, such as mortality rate, complication rate, hospital stay, and especially an endless list of biochemical mediators. Their alterations during the perioperative period have not yet been shown to be related to clinical or hermeneutic outcomes. A new method of assessment for clinical trials in endoscopic surgery and for other surgical problems is outlined, such as for surgical infections and for surgical oncology. It includes an index of recovery and objective health status assessed by the doctor, a quality-of-life self-report by the patient, and the true endpoint concept as a critical weighting of both types of outcome by patients and doctors.

Integrin-mediated signaling in human neutrophil functioning.

Integrins are important signal transducers for virtually all neutrophil functions. Although a variety of signals ultimately result in integrin activation, the intracellular targets of integrin-initiated signals are poorly delineated to date. Polymorphonuclear (PMN) leukocyte responses to inflammation are dependent on both the stimulants and the extracellular environment encountered. Integrin ligation, by cell-cell or cell-matrix interactions, activates a variety of signaling cascades. These events dictate the nature of PMN responses to the encountered stimulus. The complex system of effector molecule recruitment and permissive signaling by integrins serves to strictly regulate PMN functions such as cell adhesion, motility, oxidant production, and protein synthesis. Moreover, there is evidence that cross-talk between integrins exists to prime integrin populations for subsequent functioning. This review summarizes the current understanding of signaling mechanisms for integrin priming and activation. In this connection, the role of specific signaling molecules in key PMN functions are examined.

Clinical and scientific importance of source control in abdominal infections: summary of a symposium.

In May 1997, a panel of surgeon-investigators met to discuss the clinical importance and research implications of controlling the source of abdominal infections. It was concluded that source control is critical to therapeutic success and that antimicrobial therapy and other adjunctive interventions will fail if the source of infection is not controlled by resection, exteriorization or other means. The panelists presented different definitions of source control, depending on the scientific purpose of the definition. All participants agreed that failure to consider the adequacy of source control of infection has limited the value of most clinical trials of therapeutic anti-infective agents. Besides recognizing source control as an essential goal of patient care, the panelists emphasized the need for further investigative work to define, record and stratify the adequacy of source control in clinical trials of therapeutic agents for abdominal infections.

Cost effectiveness of ciprofloxacin plus metronidazole versus imipenem-cilastatin in the treatment of intra-abdominal infections.

OBJECTIVE: To compare the cost effectiveness of sequential intravenous (i.v.) to oral ciprofloxacin plus metronidazole (CIP/MTZ i.v./PO) with that of i.v. ciprofloxacin plus i.v. metronidazole (CIP/MTZ i.v.) and i.v. imipenem-cilastatin (IMI i.v.) in patients with intra-abdominal infections. DESIGN AND PARTICIPANTS: Patients enrolled in a double-blind randomised clinical trial were eligible for inclusion into this cost-effectiveness analysis. Decision analysis was used to characterise the economic outcomes between groups and provide a structure upon which to base the sensitivity analyses. 1996 cost values were used throughout. SETTING: The economic perspective of the analysis was that of a hospital provider. MAIN OUTCOME MEASURES AND RESULTS: Among 446 economically evaluable patients, 176 could be switched from i.v. to oral administration. The 51 patients randomised to CIP/MTZ i.v./PO who received active oral therapy had a success rate of 98%, mean duration of therapy of 9.1 days and mean cost of $US7678. There were 125 patients randomized to either CIP/MTZ i.v. or IMI i.v. who received oral placebo while continuing on active i.v. antibacterials; their success rate was 94%, mean duration of therapy was 10.1 days and mean cost was $US8774 (p = 0.029 vs CIP/MTZ i.v./PO). Of the 270 patients who were unable to receive oral administration, 97 received IMI i.v. and had a success rate of 75%, mean duration of therapy of 13.8 days and a mean cost of $US12,418, and 173 received CIP/MTZ i.v. and had a success rate of 77%, mean duration of therapy of 13.4 days and mean cost of $US12,219 (p = 0.26 vs IMI i.v.). CONCLUSIONS: In patients able to receive oral therapy, sequential i.v. to oral treatment with ciprofloxacin plus metronidazole was cost effective compared with full i.v. courses of ciprofloxacin plus metronidazole or imipenem-cilastatin. In patients unable to receive oral therapy, no difference in mean cost was found between i.v. imipenem-cilastatin or i.v. ciprofloxacin plus i.v. metronidazole.

The role of oral antimicrobials for the management of intra-abdominal infections.

BACKGROUND: Oral therapy for patients with complicated intra-abdominal infections has been very limited because those patients are frequently ill and need surgery. In addition, at the time of diagnosis and initial treatment, the infection is often accompanied by ileus, gastrointestinal tract function is frequently unknown, and many patients cannot tolerate oral intake. The use of oral antimicrobials in this setting is a recent advance resulting from the availability of agents with good tissue pharmacokinetics and potent aerobic gram-negative activity. This is the first prospective blinded study of oral therapy to provide data on the characteristics of patients eligible for oral treatment and the consequences of such treatment. STUDY DESIGN: In blinded fashion, patients with complicated intra-abdominal infections were randomized to either i.v. ciprofloxacin plus metronidazole or i.v. imipenem throughout their treatment course, or i.v. ciprofloxacin plus metronidazole and treatment with oral ciprofloxacin plus metronidazole when oral feeding was resumed (CIP/MTZ i.v./oral). Physicians could switch the patient to oral therapy between 3 and 8 days after the start of i.v. treatment. RESULTS: One hundred fifty-five of 330 (47%) patients were switched to active or placebo oral therapy. Patients who received i.v./oral therapy were treated, overall, for an average of 8.6 +/- 3.6 days, with an average of 4.0 +/- 3.0 days of oral treatment. Of 46 CIP/MTZ i.v./oral patients (active oral arm), treatment failure occurred in 2 patients (4%) compared with 41 patients (23%) who were not switched to oral agents. No patient or disease features, such as Acute Physiology and Chronic Health Evaluation II score, severity of illness at study entry, organ source of infection, or duration of treatment were identified as predictors of conversion to oral treatment. CONCLUSIONS: In this first prospective examination of sequential i.v./oral therapy for complicated intra-abdominal infections, conversion to oral therapy with ciprofloxacin plus metronidazole appears as effective as continued i.v. therapy for patients able to tolerate oral feedings. Patients who can tolerate oral intake may be treated with appropriate oral antimicrobials and are not at any significant increased risk for failure.

Effect of prophylactic administration of recombinant human granulocyte colony-stimulating factor (filgrastim) on the frequency of nosocomial infections in patients with acute traumatic brain injury or cerebral hemorrhage. The Filgrastim Study Group.

OBJECTIVE: To determine whether the use of prophylactic recombinant human granulocyte colony-stimulating factor (filgrastim) reduces the frequency of nosocomial infections in patients with either acute traumatic brain injury or cerebral hemorrhage. DESIGN: Randomized, placebo-controlled, double-blind, multicenter phase II study. SETTING: Intensive care units of seven medical centers. PATIENTS: Patients with either acute traumatic brain injury or cerebral hemorrhage who were intubated within 6 hrs of admission and who were expected to be ventilated for >72 hrs. INTERVENTIONS: Patients were randomized to receive daily subcutaneous injections of placebo (n = 21) or one of two doses of filgrastim (75 microg [n = 20] or 300 microg [n = 20]) for 10 days or until the absolute neutrophil count was >75,000 cells/mm3 or until extubation. MEASUREMENTS AND MAIN RESULTS: End points included increase in absolute neutrophil count, safety of filgrastim, and frequency of nosocomial infections (pneumonia, bacteremia, and urinary tract infection). Filgrastim caused a dose-dependent increase in absolute neutrophil count. There were no differences in the frequency of pneumonia or urinary tract infection; however, there was a dose-dependent decrease in the frequency of bacteremias (p < .05). Adverse events were similar among the three groups. There was one case of acute respiratory distress syndrome in the placebo group. CONCLUSION: In this patient population, use of filgrastim was safe and the agent appeared to reduce the risk of primary bacteremias but had no beneficial effects on mortality, length of stay, or other nosocomial infections.

A randomized, double-blind clinical trial comparing cefepime plus metronidazole with imipenem-cilastatin in the treatment of complicated intra-abdominal infections. Cefepime Intra-abdominal Infection Study Group.

OBJECTIVE: 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. DESIGN: Prospective, randomized, double-blind multicenter study. SETTING: University-affiliated hospitals in the United States and Canada. PATIENTS: Three hundred twenty-three patients with complicated intra-abdominal infections in whom an operative procedure or percutaneous drainage was required for diagnosis and management. INTERVENTION: 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. RESULTS: 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%). CONCLUSION: The combination of cefepime plus metronidazole is safe and effective therapy for patients with severe intra-abdominal infections.

Timing of treatment for nonneutropenic patients colonized with Candida.

There has been a continuing evolution of the clinical spectrum of Candida infection in nonneutropenic patients. With better understanding of the predisposing factors for fungemia in critically ill patients, interest now centers on indications for early therapy, prior to the progression of colonization to fungemia. Recent prospective trials have identified persistence of Candida species in repetitive cultures of various sites as an essential if not necessary precursor for fungemia. Treatment for patients requiring prolonged intensive-care-unit residence and demonstrating colonization with Candida is suggested, based on the frequency with which such patients progress to fungemia. The efficacy of such treatment is undocumented, and clinical trials of various regimens of polyene or azole antifungals is needed.