Community-acquired Complicated Intra-abdominal Infections Research Articles

Antimicrobial Resistance and Molecular Patterns in Community-acquired Complicated Intra-abdominal Infections: A Multicentric Study

Antimicrobial Resistance and Molecular Patterns in Community-acquired Complicated Intra-abdominal Infections: A Multicentric Study

An Evaluation of Treatment Patterns and Associated Outcomes Among Adult Hospitalized Patients With Lower-Risk Community-Acquired Complicated Intra-abdominal Infections: How Often Are Expert Guidelines Followed?

BackgroundExpert guidelines discourage use of antipseudomonal β-lactams and fluoroquinolones in lower-risk patients with community-acquired complicated intra-abdominal infection (CA cIAI). Compliance with these recommendations across US hospitals is unclear. This study sought to determine treatment patterns and associated outcomes among adult hospitalized lower-risk patients with CA cIAI.MethodsA study using data from the Premier Healthcare Database (10/2015–12/2017) was performed. Inclusion criteria: age ≥18 years; hospitalized; had a cIAI at admission; and received antibiotics within the first 4 hospital days. Patients were excluded if they were high risk, were transferred from another health care facility, had a recent hospital admission, or received dialysis within 30 days of admission. Empiric antibiotic treatment patterns and associated outcomes were quantified.ResultsOverall, 46 722 (66%) patients with cIAIs met the lower-risk CA IAI study criteria. Among lower-risk CA IAI patients, the mean (SD) age was 53.4 (18.2) years, and 71% had a Charlson Comorbidity Index score of 0. The most common diagnosis was acute appendicitis with peritonitis (59.7%). Among lower-risk CA IAI patients, 54% received piperacillin/tazobactam, 20% received a fluoroquinolone (FQ), 11% received ceftriaxone, and 7% received ampicillin/sulbactam. Overall, the median hospital length of stay was 4 days and median costs were $12 345 USD. Nearly 90% of patients were discharged home, and <1% died. Outcomes were similar across all empiric treatments received.ConclusionsOveruse of antipseudomonal β-lactams and fluoroquinolones was commonplace among lower-risk CA IAI patients. These findings can serve as the basis for an antimicrobial stewardship initiative in hospitals aspiring to reduce the use of broad-spectrum antibiotics.

PIN41 - Cost-Effectiveness Evaluation of Ertapenem in the Treatment of Adult Patients with Community-Acquired Complicated Intraabdominal Infection

To evaluate the cost-effectiveness of ertapenem versus piperaciliin/tazobactam and ceftriaxone/metronidazole in the treatment of patients with community-acquired complicated intraabdominal infections (IAI) in Colombia. For the cost-effectiveness analysis a previous published model that simulates the natural history of the disease, was adapted to Colombia setting. A systematic review of literature was done to extract the clinical data of safety and effectiveness for ertapenem in the prevention of complications and other health outcomes associated with IAI. The susceptibility profile of the different pathogens was described from Colombia SMART data, and clinical efficacy was adjusted by the distribution of pathogens in Colombia. Cost data were obtained from a database of a Colombian insurer and official lists for drugs prices. The economic evaluation was performed under the third payer perspective. A probabilistic sensitivity analysis was done using a Montecarlo simulation with 1,000 iterations, furthermore, an univariate sensitivity analysis was estimated by a tornado diagram. The effectiveness obtained after the adjustment (proportion of IAI cases successfully treated) was 89% for ertapenem, 73.6% for piperacilin/tazobactam, and 86% for ceftriaxone/metronidazole. In the cost-effectiveness evaluation, the cost generated to treat of a patient with IAI with ertapenem was COP $9,310,566 while with piperacilin/tazobactam was of COP $10,085,603 and with ceftriaxone/metronidazol COP$ $9,444,063. It is estimated that gaining 15.7% and 3.4% additional effectiveness units (clinical success case) costs COP$775,037 and COP$133,497 less with ertapenem, compared to piperacilin/tazobactam y ceftriaxone/metronidazole, repectively. In Colombia, IAI treatment with ertapenem is cost saving when compared with piperaciclin/tazobactam and ceftriaxone/metronidazole.

PIN81 - Cost-Effectiveness Analysis of the Application of Ertapenem for the Treatment of Community-Acquired Complicated Intra-Abdominal Infections

PIN81 - Cost-Effectiveness Analysis of the Application of Ertapenem for the Treatment of Community-Acquired Complicated Intra-Abdominal Infections

Clinical characteristics of patients with community-acquired complicated intra-abdominal infections: A prospective, multicentre, observational study

In this prospective, observational, multicentre study using data from five countries (Columbia, The Philippines, Portugal, Taiwan and Thailand), the clinical impact of extended-spectrum β-lactamase (ESBL)-producing organisms on hospitalised patients with community-acquired complicated intra-abdominal infections (CA-cIAIs) was compared with that of non-ESBL-producing organisms during the period April 2010 to December 2011. Adult patients (aged ≥18 years) requiring surgery or percutaneous drainage were enrolled and were followed during the first hospitalisation course. An unadjusted statistical comparison of risk factors for ESBL-positive and ESBL-negative patients was performed. Multivariate regression analyses were performed to assess whether length of stay (LOS) in hospital, clinical cure rate and some important clinical characteristics were associated with ESBL positivity. During the study period, a total of 105 adult patients from five countries were enrolled, of whom 17 (16.2%) had CA-cIAI due to ESBL-positive organisms and 88 (83.8%) had CA-cIAI due to ESBL-negative organisms. Escherichia coli was isolated in 73.3% of all samples. Infections were cured in 8 (47.1%) of the patients with CA-cIAI due to ESBL-positive organisms and in 59 (67.0%) of the patients with CA-cIAI due to ESBL-negative organisms (P=0.285). The median LOS was 11.6 days for patients with infections due to ESBL-negative organisms and 17.6 days for patients with infections due to ESBL-positive organisms (P=0.011). Multivariate logistic regression analysis revealed that pre-existing co-morbidities, but not ESBL positivity, were adversely associated with clinical cure of CA-cIAIs. In contrast, duration of hospitalisation was longer for patients with CA-cIAI due to ESBL-positive organisms.

Cost of care and antibiotic prescribing attitudes for community-acquired complicated intra-abdominal infections in Italy: a retrospective study.

IntroductionComplicated intra-abdominal infections (cIAIs) are a common cause of morbidity worldwide, and in spite of improvements in patient care, therapeutic failure still occurs, impacting in-hospital resource consumption. This study aimed to assess the costs associated with the treatment of community-acquired cIAIs, from the Italian National Health Service perspective.MethodsThis retrospective study analyzed the charts of patients who were discharged from four Italian university hospitals between January 1 and December 31, 2009 with a primary diagnosis of community-acquired cIAIs. Patient characteristics, diagnosis, surgical procedure, antibiotic therapy, and length of hospital stay were all recorded and the cost of total hospital care was estimated. Costs were calculated in Euros at 2009 values.ResultsThe records of 260 patients (mean age 48.9 years; 57% males) were analyzed. The average cost of care for a patient hospitalized due to cIAI was €4385 (95% CI 3650–5120), with an average daily cost of €419 (95% CI 378–440). Antibiotic therapy represented just under half (44.3%) of hospitalization costs. The strongest predictor of the increase in hospital costs was clinical failure: patients who clinically failed received an average of 8.2 additional days of antibiotic therapy and spent 11 more days in hospital compared with patients who responded to first-line therapy (both p < 0.05 vs. patients who were successfully treated). Furthermore, they incurred €5592 in additional hospitalization costs (2.88 times the cost associated with clinical success) with 53% (€2973) of the additional costs attributable to antibiotic therapy. Overall, antibiotic appropriateness rate was 78.8% (n = 205), and was significantly higher in patients receiving combination therapy compared with those treated with monotherapy (97.3% vs. 64.6%).ConclusionThe results of this study suggest that hospitals need to be aware of the clinical and economic consequences of antibiotic therapy of cIAIs and to reduce overall resource use and costs by improving the rate of success with appropriate initial empiric therapy.

Phase 2, Randomized, Double-Blind Study of the Efficacy and Safety of Two Dose Regimens of Eravacycline versus Ertapenem for Adult Community-Acquired Complicated Intra-Abdominal Infections

Eravacycline is a novel fluorocycline, highly active against Gram-positive and Gram-negative pathogens in vitro, including those with tetracycline and multidrug resistance. This phase 2, randomized, double-blind study was conducted to evaluate the efficacy and safety of two dose regimens of eravacycline compared with ertapenem in adult hospitalized patients with complicated intra-abdominal infections (cIAIs). Patients with confirmed cIAI requiring surgical or percutaneous intervention and antibacterial therapy were randomized (2:2:1) to receive eravacycline at 1.5 mg/kg of body weight every 24 h (q24h), eravacycline at 1.0 mg/kg every 12 h (q12h), or ertapenem at 1 g (q24h) for a minimum of 4 days and a maximum of 14 days. The primary efficacy endpoint was the clinical response in microbiologically evaluable (ME) patients at the test-of-cure (TOC) visit 10 to 14 days after the last dose of study drug therapy. Overall, 53 patients received eravacycline at 1.5 mg/kg q24h, 56 received eravacycline at 1.0 mg/kg q12h, and 30 received ertapenem. For the ME population, the clinical success rate at the TOC visit was 92.9% (39/42) in the group receiving eravacycline at 1.5 mg/kg q24h, 100% (41/41) in the group receiving eravacycline at 1.0 mg/kg q12h, and 92.3% (24/26) in the ertapenem group. The incidences of treatment-emergent adverse events were 35.8%, 28.6%, and 26.7%, respectively. Incidence rates of nausea and vomiting were low in both eravacycline groups. Both dose regimens of eravacycline were as efficacious as the comparator, ertapenem, in patients with cIAI and were well tolerated. These results support the continued development of eravacycline for the treatment of serious infections, including those caused by drug-resistant Gram-negative pathogens. (This study has been registered at ClinicalTrials.gov under registration no. NCT01265784.).

Prospective, Randomized, Study of Ampicillin-Sulbactam versus Moxifloxacin Monotherapy for the Treatment of Community-Acquired Complicated Intra-Abdominal Infections

The ideal antimicrobial treatment for intra-abdominal infections (IAIs) in the setting of fast-paced emergency departments (EDs) should be effective, convenient, and of limited resource utilization. Antibiotic monotherapy is a feasible option for this. We conducted a study in which we compared two regimens for antibiotic monotherapy recommended by published guidelines in ED patients with community-acquired, complicated IAIs (cIAIs). The study was a prospective, randomized, study of ampicillin-sulbactam versus moxifloxacin for cIAIs. After the diagnosis of cIAI was established, patients were assigned randomly to receive either moxifloxacin 400 mg intravenously (IV) qd followed by moxifloxacin 400 mg orally (PO) qd, or ampicillin-sulbactam 1.5 g IV qid followed by ampicillin-sulbactam 750 mg PO q12h. Source control procedures were used for all patients and all had complete follow-up. The primary efficacy variable for the study was the clinical response at the test-of-cure visit. A total of 116 patients were enrolled for prospective evaluation and randomized assignment to treatment with ampicillin-sulbactam (n=55) or moxifloxacin (n=61). At the test-of-cure evaluation, the overall clinical failure rate was 13.8%. The clinical failure rates in the ampicillin-sulbactam and moxifloxacin groups were 16.4% (9/55) and 11.5% (7/61), respectively (p=0.446). With regard to infection site, the clinical failure rate in cIAIs consisting of lower gastrointestinal (GI) tract infection was significantly lower in the moxifloxacin than in the ampicillin-sulbactam group (4.3% vs. 19.6%; p=0.024). According to multivariable analysis, independent risk factors for treatment failure were the time to ED presentation >24 h (odds ratio [OR] 6.8; 95% CI 1.3-36.2; p=0.024) and ampicillin-sulbactam therapy (OR 9.5; 95% CI 1.1-76.6; p=0.033). A significant difference existed in the clinical responses of the two groups. As compared with ampicillin-sulbactam, moxifloxacin was more effective for the treatment of community-acquired cIAIs of the lower GI tract. A higher risk of treatment failure for antibiotic therapy was found for patients presenting to the ED with symptoms of cIAIs lasting >24 h. Alternative antimicrobial agents should be considered for treating these patients.

Complicated Intra-Abdominal Infections Observational European study (CIAO Study)

Complicated intra-abdominal infections are frequently associated with poor prognoses and high morbidity and mortality rates.Despite advances in diagnosis, surgery, and antimicrobial therapy, mortality rates associated with complicated intra-abdominal infections remain exceedingly high.In order to describe the clinical, microbiological, and management-related profiles of both community-acquired and healthcare-acquired complicated intra-abdominal infections (IAIs), the World Society of Emergency Surgery (WSES), in collaboration with the Surgical Infections Society of Europe (SIS-E) and other prominent European surgical societies, has designed the CIAO study.The CIAO study is a multicenter, observational study and will be carried out in various surgical departments throughout Europe. The study will include patients undergoing surgery or interventional drainage for complicated IAI.

Clinical Update on the Use of Moxifloxacin in the Treatment of Community-Acquired Complicated Intraabdominal Infections

Community-acquired complicated intraabdominal infections (cIAIs) present problems for clinicians and have substantial impact on hospital resources. Because of the polymicrobial nature of these infections, successful management of cIAIs depends on timely and appropriate use of antisepsis and antiinfective strategies. The literature pertinent to this article was reviewed. The Surgical Infection Society and the Infectious Disease Society of America guidelines recommend a variety of single and combined antimicrobial therapies, including fluoroquinolone therapy, for prophylactic and definitive treatment of cIAIs with different severities. Moxifloxacin, a fluoroquinolone, demonstrates a broad spectrum of antimicrobial (including anaerobic) activity, good tissue penetration into the gastrointestinal tract, and a good tolerability profile. Clinical data also have demonstrated that moxifloxacin is effective as monotherapy for patients with cIAIs. This review identifies the clinical issues impacting antimicrobial selection in cIAI and discusses data on the role of moxifloxacin in light of the current guidelines for management of these patients. Moxifloxacin provides clinicians with a convenient monotherapy option for the treatment of mild-to-moderate cIAIs.

Complicated Intra-abdominal Infections: A Focus on Appendicitis and Diverticulitis

Severe abdominal pain is a common complaint encountered by primary care and emergency room physicians. Caused by many conditions, including appendicitis and diverticulitis, severe abdominal pain may be a diagnostic challenge. Although different in many ways, appendicitis and diverticulitis are caused by obstruction of a blind pouch that leads to inflammation of the structure and surrounding tissue. Appendicitis and diverticulitis are 2 of the most frequently diagnosed causes of complicated intra-abdominal infections. Combined, appendicitis and diverticulitis comprise > 80% of all community-acquired complicated intra-abdominal infections. These conditions are serious and require prompt diagnosis and treatment. Because complicated intra-abdominal infections are typically polymicrobial, a wide variety of causative pathogens are identified, including Gram-positive and Gram-negative aerobic and anaerobic microorganisms. Treatment for these disorders often requires surgical and medical management. Although surgical intervention can be the definitive treatment for complicated intra-abdominal infections, successful management of appendicitis and diverticulitis will depend on appropriate selection of antimicrobials and optimal duration of therapy to maximize the coverage of potential causative pathogens and to minimize the development of resistance. Guidelines for empiric treatment of complicated intra-abdominal infections recommend broad-spectrum antimicrobials as monotherapy or in combinations, including standard antimicrobial regimens, such as piperacillin/tazobactam, imipenem/cilastatin, and piperacillin-tazobactam/amoxicillin-clavulanate regimens, and fluoroquinolone-based regimens. This review article compares the presentations and treatments of these common complicated intra-abdominal infections.

Cost-Effectiveness Evaluation of Ertapenem versus Piperacillin/Tazobactam in the Treatment of Complicated Intraabdominal Infections Accounting for Antibiotic Resistance

Objective To evaluate the cost-effectiveness of ertapenem versus piperacillin/tazobactam in the treatment of community-acquired complicated intraabdominal infections accounting for development of antibiotic resistance in the Dutch setting. Methods A decision tree was developed to estimate cost-effectiveness of ertapenem versus piperacillin/tazobactam at different time points after introduction of treatment. Development of resistance was incorporated using a compartment model. Resistance was a function of the eradication rate of pathogens and antibiotic prescription. Model outcomes included quality-adjusted life years (QALYs), direct costs and cost per QALY saved. Microbiological eradication rate, clinical success, and costs were derived from literature. The analyses included pathogens with intrinsic or acquired resistance. Results The model suggested overall savings of €355 (95% uncertainty interval €480; €1205) per patient when abdominal infections are treated with ertapenem instead of piperacillin/tazobactam. Probabilistic sensitivity analysis found a 94% probability of the incremental cost per QALY saved being within the generally accepted threshold for cost-effectiveness (€20,000). After 5 years, it is expected that antibiotic resistance with piperacillin/tazobactam has increased with a greater rate compared to ertapenem, and cost-savings with ertapenem are expected to increase to €672 (€−232; €1617). Ertapenem will, in addition, result in greater success rates and in QALY savings (0.17; 0.07–0.30). Alternative scenarios, with lower levels of initial resistance confirm the cost savings with ertapenem. Conclusion Given the underlying assumptions and data used, this evaluation demonstrated that ertapenem is a cost saving and possibly an economically dominant therapy over piperacillin/tazobactam for the treatment of community-acquired intraabdominal infections in The Netherlands.

Community-acquired complicated intra-abdominal infections in children hospitalized during 1995–2004 at a paediatric surgery department

Information on the epidemiologic, clinical, microbiologic and therapeutic aspects of community-acquired complicated intra-abdominal infections in paediatrics is limited. The objectives of this study were to investigate the epidemiologic, clinical, microbiologic and therapeutic characteristics of community-acquired complicated intra-abdominal infections occurring in children aged 1 month-15 y. Medical charts and microbiology data of all children hospitalized with complicated intra-abdominal infections were retrospectively examined. Complicated intra-abdominal infections were defined as infections extending beyond the viscus of origin into the peritoneal space, with subsequent development of abscess or peritonitis. One hundred and twenty-three patients with complicated intra-abdominal infections (99/123, 80% >5 y of age) were included; 113 (92%) had complicated acute appendicitis. Twelve (10%) patients underwent computerized tomography-guided percutaneous drainage of periappendicular abscesses. The mean rate of complicated intra-abdominal infections among patients with complicated acute appendicitis was 10% without significant changes during the study years. Positive intra-abdominal cultures were recorded in 97/108 (90%) evaluable patients; 65/97 (67%) cases were characterized by mixed bacterial flora growth. One hundred and ninety pathogens (aerobes n=164, 86%; anaerobes n=26, 14%) were isolated. Escherichia coli was the most common pathogen (94 isolates, 57%). In vitro amoxicillin/clavulanate coverage of E. coli and Klebsiella spp was modest (81% and 86%, respectively). The ampicillin/gentamicin/metronidazole regimen was more appropriate in vitro than the amoxicillin/clavulanate regimen (3/80, 4% resistant pathogens compared with 8/43, 19%; p=0.02). Post-operative complications were recorded in 33/123 (27%) patients. Time until defervescence to < 37.5 degrees C was shorter in children with periappendicular abscess than in children with generalized peritonitis (6+/-4 vs 4+/-3 days; p=0.009). (1) most community-acquired complicated intra-abdominal infections occurred as a result of acute appendicitis; (2) the rate of complicated intra-abdominal infections among patients with acute appendicitis was low and without significant changes during the study period; (3) E. coli was the most frequently isolated pathogen; (4) amoxicillin/clavulanate provided only partial coverage for complicated intra-abdominal infection pathogens and should be used with caution in the empiric treatment of complicated intra-abdominal infections.

P1400 Pharmaco-economic impact accounting for future resistance of ertapenam vs. piperacillin/tazobactam in the treatment of community-acquired complicated intra-abdominal infections in the Netherlands

P1400 Pharmaco-economic impact accounting for future resistance of ertapenam vs. piperacillin/tazobactam in the treatment of community-acquired complicated intra-abdominal infections in the Netherlands

Discussion on: “Development and Experimental Verification of a Mobile Client-Centric Networked Controlled System”

In this prospective, observational, multicentre study using data from five countries (Columbia, The Philippines, Portugal, Taiwan and Thailand), the clinical impact of extended-spectrum β-lactamase (ESBL)-producing organisms on hospitalised patients with community-acquired complicated intra-abdominal infections (CA-cIAIs) was compared with that of non-ESBL-producing organisms during the period April 2010 to December 2011. Adult patients (aged ≥18 years) requiring surgery or percutaneous drainage were enrolled and were followed during the first hospitalisation course. An unadjusted statistical comparison of risk factors for ESBL-positive and ESBL-negative patients was performed. Multivariate regression analyses were performed to assess whether length of stay (LOS) in hospital, clinical cure rate and some important clinical characteristics were associated with ESBL positivity. During the study period, a total of 105 adult patients from five countries were enrolled, of whom 17 (16.2%) had CA-cIAI due to ESBL-positive organisms and 88 (83.8%) had CA-cIAI due to ESBL-negative organisms. Escherichia coli was isolated in 73.3% of all samples. Infections were cured in 8 (47.1%) of the patients with CA-cIAI due to ESBL-positive organisms and in 59 (67.0%) of the patients with CA-cIAI due to ESBL-negative organisms (P = 0.285). The median LOS was 11.6 days for patients with infections due to ESBL-negative organisms and 17.6 days for patients with infections due to ESBL-positive organisms (P = 0.011). Multivariate logistic regression analysis revealed that pre-existing co-morbidities, but not ESBL positivity, were adversely associated with clinical cure of CA-cIAIs. In contrast, duration of hospitalisation was longer for patients with CA-cIAI due to ESBL-positive organisms.