Adequate Source Control Research Articles

Inadequate Source Control and Inappropriate Antibiotics are Key Determinants of Mortality in Patients with Intra-Abdominal Sepsis and Associated Bacteremia.

Patients with intra-abdominal sepsis and associated bacteremia have a high mortality rate. However, outcomes studies in this population are limited, in part because of the small numbers of such patients. The objective of this study was to describe characteristics of critically ill patients with secondary blood stream infection (BSI) of intra-abdominal origin and identify predictors of mortality. This retrospective, single-center study evaluated patients admitted between January 2005 and January 2011 with bacteremia because of an intra-abdominal source. Patients were included if they met criteria for severe sepsis based on International Classification of Diseases, 9th Revision (ICD 9) codes for acute organ dysfunction, had a positive blood culture, had at least one ICD 9 code indicative of an intra-abdominal process, and had a confirmed or clinically suspected intra-abdominal infection (IAI) within 72 h of the blood culture. Chart review was performed to confirm the presence of these criteria and also the absence of any other potential source of bacteremia. Data were collected on patient demographics, BSI source, source control procedure details, microorganisms isolated, and antibiotics administered. Multivariable logistic regression analysis was performed to identify independent predictors of mortality. Three hundred six patients with BSI were identified, of which 108 episodes were deemed to be of intra-abdominal origin. Gram-negative organisms comprised 43% of blood isolates, followed by gram-positives (33%), anaerobes (14%), and yeast (9%). Appropriate antimicrobial therapy was administered in 71% of patients. The overall mortality rate was 27.8%. As compared with survivors, non-survivors were older, more likely to have underlying COPD or asthma, and have renal or metabolic failure (p<0.05 for all). Among non-survivors, adequate source control was obtained less frequently (64% vs. 91%, p=0.002) and median time to appropriate antibiotics was longer (23 h vs. 4 h, p=0.004). Logistic regression analysis revealed inadequate source control (p=0.002) and inappropriate antibiotics (p=0.016) to be independently associated with mortality. Critically ill patients with a BSI of abdominal origin are at high risk for mortality. Failure to achieve adequate source control and administration of inappropriate antibiotics were independent predictors of mortality. Thus, these represent potential opportunities to impact outcomes in patients with complicated IAI.

Antimicrobial and surgical management of intra-abdominal infections in children

Complicated intra-abdominal infections are a common problem in children. The etiology of these infections varies by age, with necrotizing enterocolitis being the most common cause in neonates, and appendicitis the most common cause in children. Diagnosis is based on clinical and laboratory findings as well as appropriate imaging studies. These infections are generally the result of mixed gastrointestinal flora, most commonly Escherichia coli and Bacteroides spp. The basic treatment principles for complicated intra-abdominal infections include adequate hemodynamic resuscitation, appropriate antimicrobial therapy, and source control. Antibiotic regimens should include agents effective against common Gram-negative facultative/aerobic bacilli as well as anaerobes. Increased antibiotic resistance has developed among several of the pathogens involved in these infections, which may need to be taken into consideration when selecting empiric therapy. In addition to appropriate antimicrobial therapy, adequate source control has been considered essential in the management of these infections. However, the need for definitive source control procedures in all patients has been challenged, and it has been demonstrated that deferral of these procedures or use of drainage instead of definitive procedures may suffice in selected children and neonates. The advent of laparoscopic procedures has also allowed less invasive approaches to be used in managing the nidus of infection. In this review, some aspects of the etiology, diagnosis and treatment of pediatric intra-abdominal infections will be addressed, particularly with regard to controversies in the use of antimicrobial therapy and source control procedures for these infections.

Trial of Short-Course Antimicrobial Therapy for Intraabdominal Infection

BackgroundThe successful treatment of intraabdominal infection requires a combination of anatomical source control and antibiotics. The appropriate duration of antimicrobial therapy remains unclear.MethodsWe randomly assigned 518 patients with complicated intraabdominal infection and adequate source control to receive antibiotics until 2 days after the resolution of fever, leukocytosis, and ileus, with a maximum of 10 days of therapy (control group), or to receive a fixed course of antibiotics (experimental group) for 4±1 calendar days. The primary outcome was a composite of surgical-site infection, recurrent intraabdominal infection, or death within 30 days after the index source-control procedure, according to treatment group. Secondary outcomes included the duration of therapy and rates of subsequent infections.ResultsSurgical-site infection, recurrent intraabdominal infection, or death occurred in 56 of 257 patients in the experimental group (21.8%), as compared with 58 of 260 patients in the control group (22.3%) (absolute difference, −0.5 percentage point; 95% confidence interval [CI], −7.0 to 8.0; P=0.92). The median duration of antibiotic therapy was 4.0 days (interquartile range, 4.0 to 5.0) in the experimental group, as compared with 8.0 days (interquartile range, 5.0 to 10.0) in the control group (absolute difference, −4.0 days; 95% CI, −4.7 to −3.3; P<0.001). No significant between-group differences were found in the individual rates of the components of the primary outcome or in other secondary outcomes.ConclusionsIn patients with intraabdominal infections who had undergone an adequate source-control procedure, the outcomes after fixed-duration antibiotic therapy (approximately 4 days) were similar to those after a longer course of antibiotics (approximately 8 days) that extended until after the resolution of physiological abnormalities. (Funded by the National Institutes of Health; STOP-IT ClinicalTrials.gov number, NCT00657566.)

A multicenter multinational study of abdominal candidiasis: epidemiology, outcomes and predictors of mortality.

Clinical data on patients with intra-abdominal candidiasis (IAC) is still scarce. We collected data from 13 hospitals in Italy, Spain, Brazil, and Greece over a 3-year period (2011-2013) including patients from ICU, medical, and surgical wards. A total of 481 patients were included in the study. Of these, 27% were hospitalized in ICU. Mean age was 63 years and 57% of patients were male. IAC mainly consisted of secondary peritonitis (41%) and abdominal abscesses (30%); 68 (14%) cases were also candidemic and 331 (69%) had concomitant bacterial infections. The most commonly isolated Candida species were C. albicans (n = 308 isolates, 64%) and C. glabrata (n = 76, 16%). Antifungal treatment included echinocandins (64%), azoles (32%), and amphotericin B (4%). Septic shock was documented in 40.5% of patients. Overall 30-day hospital mortality was 27% with 38.9% mortality in ICU. Multivariate logistic regression showed that age (OR 1.05, 95% CI 1.03-1.07, P < 0.001), increments in 1-point APACHE II scores (OR 1.05, 95% CI 1.01-1.08, P = 0.028), secondary peritonitis (OR 1.72, 95% CI 1.02-2.89, P = 0.019), septic shock (OR 3.29, 95% CI 1.88-5.86, P < 0.001), and absence of adequate abdominal source control (OR 3.35, 95% CI 2.01-5.63, P < 0.001) were associated with mortality. In patients with septic shock, absence of source control correlated with mortality rates above 60% irrespective of administration of an adequate antifungal therapy. Low percentages of concomitant candidemia and high mortality rates are documented in IAC. In patients presenting with septic shock, source control is fundamental.

Science, Medicine, and the Anesthesiologist

Science, Medicine, and the Anesthesiologist

Empiric Antibiotic Treatment Reduces Mortality in Severe Sepsis and Septic Shock From the First Hour

Compelling evidence has shown that aggressive resuscitation bundles, adequate source control, appropriate antibiotic therapy, and organ support are cornerstone for the success in the treatment of patients with sepsis. Delay in the initiation of appropriate antibiotic therapy has been recognized as a risk factor for mortality. To perform a retrospective analysis on the Surviving Sepsis Campaign database to evaluate the relationship between timing of antibiotic administration and mortality. Retrospective analysis of a large dataset collected prospectively for the Surviving Sepsis Campaign. One hundred sixty-five ICUs in Europe, the United States, and South America. A total of 28,150 patients with severe sepsis and septic shock, from January 2005 through February 2010, were evaluated. Antibiotic administration and hospital mortality. A total of 17,990 patients received antibiotics after sepsis identification and were included in the analysis. In-hospital mortality was 29.7% for the cohort as a whole. There was a statically significant increase in the probability of death associated with the number of hours of delay for first antibiotic administration. Hospital mortality adjusted for severity (sepsis severity score), ICU admission source (emergency department, ward, vs ICU), and geographic region increased steadily after 1 hour of time to antibiotic administration. Results were similar in patients with severe sepsis and septic shock, regardless of the number of organ failure. The results of the analysis of this large population of patients with severe sepsis and septic shock demonstrate that delay in first antibiotic administration was associated with increased in-hospital mortality. In addition, there was a linear increase in the risk of mortality for each hour delay in antibiotic administration. These results underscore the importance of early identification and treatment of septic patients in the hospital setting.

An introduction of Tertiary Peritonitis

Intraperitoneal infection known as peritonitis is a major killer in the practice of clinical surgery. Tertiary peritonitis (TP) may be defined as intra-abdominal infection that persists or recurs ³48 h following successful and adequate surgical source control. A planned or on-demand relaparotomy after an initial operation is probably most frequent way to diagnose TP, but is a late event to occur. Hence it is desirable to have timely and nonoperative diagnosis of TP after the initial operation and subsequent initiation of an appropriate therapy to reduce the complications and to improve the outcome.

The Use of Cefepime for Treating AmpC β-Lactamase–Producing Enterobacteriaceae

AmpC β-lactamase-producing organisms are associated with significant morbidity and mortality. Induction of resistance to third-generation cephalosporins after exposure to these agents complicates treatment options and carbapenems are considered optimal therapy. The role of cefepime, however, remains unclear. Our objective was to compare clinical outcomes for patients receiving cefepime compared with meropenem for invasive infections caused by organisms expressing AmpC β-lactamases. Hospitalized patients with blood, bronchoalveolar lavage, or intra-abdominal fluid cultures growing Enterobacter spp, Serratia spp, or Citrobacter spp were evaluated using the cefotetan-boronic acid disk test and the cefotetan-cloxacillin Etest to identify organisms with AmpC β-lactamase production from February 2010 to January 2011. In patients with organisms hyperproducing AmpC β-lactamases (positive by both methods), clinical outcomes for patients receiving cefepime or meropenem therapy were compared. To minimize the possibility of treatment selection bias, 1:1 nearest neighbor propensity score matching was performed prior to regression analysis. Of 399 patients meeting eligibility criteria, 96 (24%) had confirmed infections with AmpC β-lactamase-producing organisms. Propensity score matching of patients infected with AmpC β-lactamase-positive organisms treated with cefepime or meropenem yielded 32 well-balanced patient pairs with no difference in 30-day mortality (odds ratio, 0.63; 95% confidence interval [CI], .23-2.11; P = .36) or length of hospital stay after infection (relative risk, 0.96; 95% CI, .79-1.26; P = .56) between the 2 groups. Cefepime may be a reasonable option for the treatment of invasive infections due to AmpC β-lactamase-producing organisms, particularly when adequate source control is achieved.

Perioperative treatment of patients with sepsis

Key elements in the initial resuscitation and stabilization of the patient with sepsis are fluid therapy, vasopressor or inotropic support, administration of adequate antibiotics and source control. This review will primarily discuss fluid, vasopressor and antibiotic therapy because these have been the subject of the recent large clinical trials. On the basis of the recent large randomized clinical trials, starch solutions should be avoided in patients with sepsis because there is no evidence of benefit and clear signals of harm including adverse effects on kidney and haemostatic function and increased mortality in one trial. Ongoing trials are investigating the efficacy and safety of albumin and red blood cell transfusion in patients with sepsis. Norepinephrine should be the first-line vasopressor agent because accumulating evidence shows more adverse events with the use of dopamine. Early initiation of adequate antibiotic therapy is recommended and etomidate should not be used in patients with sepsis. Recent high-quality trials in the intensive care setting have provided data to improve the treatment and thereby the outcome of patients with sepsis. These findings may be used in the perioperative setting to minimize the harmful effects of specific interventions.

Candidemia in Neurosurgical Intensive Care Unit: preliminary analysis of the effect of topical Nystatin prophylaxis and adequate source control on patients with early tracheostomy intubation.

The present study represents a preliminary evaluation of the impact of topical nystatin prophylaxis administration and adequate CVC management on reducing the chance of developing candidemia in neurosurgical intensive care unit (NICU) patients. We conducted a case-control study at the nine bed NICU of the Policlinico "Umberto I" teaching hospital in Rome, Italy, during the period from January 2011 to July 2012. We compared eight patients with culture proven Candida bloodstream infection (CBSI) with a control group of 19 patients who did not have evidence of CBSI. When the CBSI group was compared with the control group, the former were more likely than controls to not have received nystatin prophylaxis and adequate catheter care (p= 0,008). When CBSI group was matched with patients with no adequate source control and nystatin prophylaxis, average NICU stay (71.13 days vs 19.0 days) was significant (mean difference = -52.12 days, 95% CI -97.11 to -7.14, p= 0.028). The same was true for mean time of glucocorticoid exposure (mean difference = -10.5 days, 95% CI -17.35 to -3.65, p<0.01). Binary logistic regression analysis demonstrated no significant association between topical nystatin prophylaxis (p= 0.99), length of NICU stay (p= 0.99), time of glucocorticoid exposure (p= 0.99) and candidemia. Topical prophylaxis with nystatin and adequate source control proved to be effective in preventing invasive candidiasis in patients admitted to the NICU.

Septic embolism in the intensive care unit

Septic embolism encompasses a wide range of presentations and clinical considerations. From asymptomatic, incidental finding on advanced imaging to devastating cardiovascular or cerebral events, this important clinico-pathologic entity continues to affect critically ill patients. Septic emboli are challenging because they represent two insults—the early embolic/ischemic insult due to vascular occlusion and the infectious insult from a deep-seated nidus of infection frequently not amenable to adequate source control. Mycotic aneurysms and intravascular or end-organ abscesses can occur. The diagnosis of septic embolism should be considered in any patient with certain risk factors including bacterial endocarditis or infected intravascular devices. Treatment consists of long-term antibiotics and source control when possible. This manuscript provides a much-needed synopsis of the different forms and clinical presentations of septic embolism, basic diagnostic considerations, general clinical approaches, and an overview of potential complications.

Foreign Body with Gas Gangrene in an Elderly Patient with Diabetes.

A 76-year-old African-American man who lived alone, with an 11year history of poorly controlled diabetes and symptomatic peripheral neuropathy, presented to the Emergency Department with right foot pain and swelling. His initial evaluation included a lower extremity Doppler that ruled out a deep venous thrombosis and the patient was discharged. The patient returned to the Emergency Department after one week for worsening right foot pain and swelling. He was afebrile and hemodynamically stable. The physical exam revealed new unroofed blisters on the dorsal aspect of the right foot. Foot x-ray (Panel 1) showed a 3 cm linear metallic foreign body, which appeared to be a broken sewing needle in the soft tissues between distal first and second metatarsals. Computed Tomography (CT) scan (Panel 2) showed moderate air suggesting deep tissue infection, with multiple tiny gas bubbles within the proximal phalanx of the second digit, concerning for gas gangrene. He received broad-spectrum intravenous antibiotics and underwent a two-stage operation on his right leg. The first stage was a guillotine amputation. The patient remained afebrile and hemodynamically stable. Antibiotics were stopped since now, after removal of the gangrenous tissue, there was adequate source control of the infection. A few days later, he underwent a definitive, below-theknee amputation. The differential diagnoses for gas gangrene includes inflammation

Arterial Reconstruction for Atypical Mycotic Aneurysms

Our case involves a 67-year-old man with a post lung transplantation status for idiopathic pulmonary fibrosis, who was initially referred to our institution for treatment of left hip septic arthritis due to Pseudallescheria boydii infection. One month following total hip arthroplasty, he noticed left upper thigh swelling with duplex imaging consistent with a 7-cm mid-superficial femoral artery aneurysm with popliteal vein compression and associated deep venous thrombosis. During operative resection, exploration of his contralateral saphenous vein showed inadequate conduit for use. Therefore, we proceeded with proximal and distal clamp control with intraoperative arterial shunting followed by cryoarterial reconstruction after complete aneurysm sac resection and debridement. Intraoperative arterial wall cultures remained negative for bacterial pathogens; however, final operative fungal cultures once again grew Pseudallescheria boydii. Our case highlights the complexity of adequate source control with effective arterial reconstruction in these immunosuppressed patient populations, particularly with fungal organisms that historically have poor therapeutic response to medical therapy alone.

Characteristics and determinants of outcome of hospital-acquired bloodstream infections in intensive care units: the EUROBACT International Cohort Study

The recent increase in drug-resistant micro-organisms complicates the management of hospital-acquired bloodstream infections (HA-BSIs). We investigated the epidemiology of HA-BSI and evaluated the impact of drug resistance on outcomes of critically ill patients, controlling for patient characteristics and infection management. A prospective, multicentre non-representative cohort study was conducted in 162 intensive care units (ICUs) in 24 countries. We included 1,156 patients [mean ± standard deviation (SD) age, 59.5 ± 17.7 years; 65 % males; mean ± SD Simplified Acute Physiology Score (SAPS) II score, 50 ± 17] with HA-BSIs, of which 76 % were ICU-acquired. Median time to diagnosis was 14 [interquartile range (IQR), 7-26] days after hospital admission. Polymicrobial infections accounted for 12 % of cases. Among monomicrobial infections, 58.3 % were gram-negative, 32.8 % gram-positive, 7.8 % fungal and 1.2 % due to strict anaerobes. Overall, 629 (47.8 %) isolates were multidrug-resistant (MDR), including 270 (20.5 %) extensively resistant (XDR), and 5 (0.4 %) pan-drug-resistant (PDR). Micro-organism distribution and MDR occurrence varied significantly (p < 0.001) by country. The 28-day all-cause fatality rate was 36 %. In the multivariable model including micro-organism, patient and centre variables, independent predictors of 28-day mortality included MDR isolate [odds ratio (OR), 1.49; 95 % confidence interval (95 %CI), 1.07-2.06], uncontrolled infection source (OR, 5.86; 95 %CI, 2.5-13.9) and timing to adequate treatment (before day 6 since blood culture collection versus never, OR, 0.38; 95 %CI, 0.23-0.63; since day 6 versus never, OR, 0.20; 95 %CI, 0.08-0.47). MDR and XDR bacteria (especially gram-negative) are common in HA-BSIs in critically ill patients and are associated with increased 28-day mortality. Intensified efforts to prevent HA-BSIs and to optimize their management through adequate source control and antibiotic therapy are needed to improve outcomes.

Septic Shock Attributed to Candida Infection: Importance of Empiric Therapy and Source Control

Delayed treatment of candidemia has previously been shown to be an important determinant of patient outcome. However, septic shock attributed to Candida infection and its determinants of outcome have not been previously evaluated in a large patient population. A retrospective cohort study of hospitalized patients with septic shock and blood cultures positive for Candida species was conducted at Barnes-Jewish Hospital, a 1250-bed urban teaching hospital (January 2002-December 2010). Two hundred twenty-four consecutive patients with septic shock and a positive blood culture for Candida species were identified. Death during hospitalization occurred among 155 (63.5%) patients. The hospital mortality rate for patients having adequate source control and antifungal therapy administered within 24 hours of the onset of shock was 52.8% (n = 142), compared to a mortality rate of 97.6% (n = 82) in patients who did not have these goals attained (P < .001). Multivariate logistic regression analysis demonstrated that delayed antifungal treatment (adjusted odds ratio [AOR], 33.75; 95% confidence interval [CI], 9.65-118.04; P = .005) and failure to achieve timely source control (AOR, 77.40; 95% CI, 21.52-278.38; P = .001) were independently associated with a greater risk of hospital mortality. The risk of death is exceptionally high among patients with septic shock attributed to Candida infection. Efforts aimed at timely source control and antifungal treatment are likely to be associated with improved clinical outcomes.

Duration of antibiotic therapy in bacteraemia

Reducing duration of antibiotic therapy without a diminution in efficacy decreases cost, side effects, antibiotic related diarrhoea, and bacterial resistance. Havey and colleagues [1] reported the results of a systematic review and meta-analysis of antibiotic duration in bacteraemia and deduced short course therapy (<7 days) might be as effective as longer treatments. It is surprising given the obvious benefits and the frequency with which bacteraemia is documented in critically ill patients that there is such a paucity of randomised clinical trials (RCTs) comparing duration of therapy. Only one RCT, in neonates, had been performed in patients solely with bacteraemia. Accordingly, Havey and colleagues concluded that duration of antibiotic therapy in bacteraemia is poorly studied and would benefit from a large RCT. Daneman and colleagues [2] performed a survey of Canadian infectious disease and critical care specialists to gauge the optimal duration of therapy in bacteraemic critically ill patients. Considerable variability existed amongst clinicians and undoubtedly reflects the lack of robust data to guide best practice. However, length of treatment is only one aspect of optimising outcomes from antibiotic use. Future RCTs need to take into account whether adequate source control has been achieved, as this will bias duration of therapy. Moreover, it is clear that since many antibiotics deployed in critical care demonstrate time-dependent killing, inadequate doses are frequently used, which increases treatment failure and the emergence of resistance [3,4]. Pharmacokinetic optimisation that ensures adequate time above minimum inhibitory concentration should therefore be an integral component of any trial that compares duration of antibiotic therapy [5].

Intensive care unit-acquired weakness (ICUAW) and muscle wasting in critically ill patients with severe sepsis and septic shock.

Sepsis presents a major health care problem and remains one of the leading causes of death within the intensive care unit (ICU). Therapeutic approaches against severe sepsis and septic shock focus on early identification. Adequate source control, administration of antibiotics, preload optimization by fluid resuscitation and further hemodynamic stabilisation using vasopressors whenever appropriate are considered pivotal within the early—golden—hours of sepsis. However, organ dysfunction develops frequently in and represents a significant comorbidity of sepsis. A considerable amount of patients with sepsis will show signs of severe muscle wasting and/or ICU-acquired weakness (ICUAW), which describes a frequently observed complication in critically ill patients and refers to clinically weak ICU patients in whom there is no plausible aetiology other than critical illness. Some authors consider ICUAW as neuromuscular organ failure, caused by dysfunction of the motor unit, which consists of peripheral nerve, neuromuscular junction and skeletal muscle fibre. Electrophysiologic and/or biopsy studies facilitate further subclassification of ICUAW as critical illness myopathy, critical illness polyneuropathy or critical illness myoneuropathy, their combination. ICUAW may protract weaning from mechanical ventilation and impede rehabilitation measures, resulting in increased morbidity and mortality. This review provides an insight on the available literature on sepsis-mediated muscle wasting, ICUAW and their potential pathomechanisms.

A focus on intra-abdominal infections

Complicated intra-abdominal infections are an important cause of morbidity and are frequently associated with poor prognosis, particularly in higher risk patients.Well defined evidence-based recommendations for intra-abdominal infections treatment are partially lacking because of the limited number of randomized-controlled trials.Factors consistently associated with poor outcomes in patients with intra-abdominal infections include increased illness severity, failed source control, inadequate empiric antimicrobial therapy and healthcare-acquired infection.Early prognostic evaluation of complicated intra-abdominal infections is important to select high-risk patients for more aggressive therapeutic procedures.The cornerstones in the management of complicated intra-abdominal infections are both source control and antibiotic therapy.The timing and the adequacy of source control are the most important issues in the management of intra-abdominal infections, because inadequate and late control of septic source may have a negative effect on the outcomes.Recent advances in interventional and more aggressive techniques could significantly decrease the morbidity and mortality of physiologically severe complicated intra-abdominal infections, even if these are still being debated and are yet not validated by limited prospective trials.Empiric antimicrobial therapy is nevertheless important in the overall management of intra-abdominal infections. Inappropriate antibiotic therapy may result in poor patient outcomes and in the appearance of bacterial resistance.Antimicrobial management is generally standardised and many regimens, either with monotherapy or combination therapy, have proven their efficacy. Routine coverage especially against Enterococci and candida spp is not always recommended, but can be useful in particular clinical conditions. A de escalation approach may be recommended in patients with specific risk factors for multidrug resistant infections such as immunodeficiency and prolonged antibacterial exposure.Therapy should focus on the obtainment of adequate source control and adequate use of antimicrobial therapy dictated by individual patient risk factors. Other critical issues remain debated and more controversies are still open mainly because of the limited number of randomized controlled trials.

Moxifloxacin is non-inferior to combination therapy with ceftriaxone plus metronidazole in patients with community-origin complicated intra-abdominal infections

Management of community-origin complicated intra-abdominal infections (cIAIs) requires surgical intervention and antimicrobial therapy. This multinational, randomised, double-blind clinical trial carried out in Asia compared the efficacy and safety of moxifloxacin monotherapy and ceftriaxone/metronidazole combination therapy in adults with confirmed or suspected cIAI. Patients received surgical intervention and either intravenous (i.v.) moxifloxacin 400 mg once daily or i.v. ceftriaxone 2 g once daily plus i.v. metronidazole 500 mg twice daily. A total of 364 patients were randomised [intent-to-treat (ITT), moxifloxacin N = 180, comparator N = 181; per-protocol (PP), moxifloxacin N = 174, comparator N = 171]. The most common cIAI diagnosis was complicated appendicitis. Moxifloxacin was non-inferior to ceftriaxone/metronidazole in terms of clinical response at test-of-cure in the PP population [clinical cure, 90.2% for moxifloxacin vs. 96.5% for ceftriaxone/metronidazole; 95% confidence interval (CI) of the difference −11.7 to −1.7] and in the ITT population (87.2% for moxifloxacin vs. 91.2% for ceftriaxone/metronidazole; 95% CI −10.7 to 1.9). Bacteriological cure rates in the microbiologically evaluable population support the clinical results (89.4% for moxifloxacin vs. 95.9% for ceftriaxone/metronidazole; 95% CI −13.3 to −0.6). The incidence of treatment-emergent adverse events was similar for both treatment groups (moxifloxacin 31.7% vs. comparator 24.3%). These results confirm previous findings that moxifloxacin plus adequate source control is an appropriate treatment of cIAI.

Identification of Patients at Risk for Development of Tertiary Peritonitis on a Surgical Intensive Care Unit

BackgroundTertiary peritonitis (TP) is defined as a severe recurrent or persistent intra-abdominal infection after adequate surgical source control of secondary peritonitis (SP). The aim of this study was to analyze the characteristics of patients with SP who will further develop TP in order to define early diagnostic markers for TP. Study DesignOver a 1-year period, all patients on the surgical intensive care unit (ICU) with SP were prospectively assessed for the development of TP applying the definition of the ICU consensus conference. The Mannheim Peritonitis Index (MPI), C-reactive protein (CRP) and Simplified Acute Physiology Score II (SAPS II) were assessed at the initial operation (IO) that was diagnostic for SP and in the postoperative period. ResultsAmong 69 patients with SP, 15 patients further developed TP, whereas 54 patients did not develop TP. Compared to SP, patients with transition to TP had significantly higher MPI at IO (28.6 vs. 19.8; p < 0.001), relaparotomy rate (2.00 vs. 0.11; p < 0.001), mortality (60% vs. 9%; p < 0.001), duration of ICU stay (14 vs. 4 days; p < 0.005), as well as SAPS II (45.1 vs. 28.4; p < 0.005) and CRP (265 mg/dL vs. 217 mg/dL; p < 0.05) on the second postoperative day after IO. ConclusionsThe MPI at IO as well as CRP and SAPS II at the second postoperative day helps to identify patients at risk for tertiary peritonitis.