Inappropriate Empiric Antimicrobial Therapy Research Articles

Development of a risk prediction model for bloodstream infection in patients with fever of unknown origin

Bloodstream infection (BSI) is a significant cause of mortality among patients with fever of unknown origin (FUO). Inappropriate empiric antimicrobial therapy increases difficulty in BSI diagnosis and treatment. Knowing the risk of BSI at early stage may help improve clinical outcomes and reduce antibiotic overuse. We constructed a multivariate prediction model based on clinical features and serum inflammatory markers using a cohort of FUO patients over a 5-year period by Least Absolute Shrinkage and Selection Operator (LASSO) and logistic regression. Among 712 FUO patients, BSI was confirmed in 55 patients. Five independent predictors available within 24 h after admission for BSI were identified: presence of diabetes mellitus, chills, C-reactive protein level of 50-100 mg/L, procalcitonin > 0.3 ng/mL, neutrophil percentage > 75%. A predictive score incorporating these 5 variables has adequate concordance with an area under the curve of 0.85. The model showed low positive predictive value (22.6%), but excellent negative predictive value (97.4%) for predicting the risk of BSI. The risk of BSI reduced to 2.0% in FUO patients if score < 1.5. A simple tool based on 5 variables is useful for timely ruling out the individuals at low risk of BSI in FUO population.

Antimicrobial use and mortality among intensive care unit patients with bloodstream infections: implications for stewardship programs

BackgroundBloodstream infections (BSIs) are one of the most critical illnesses requiring intensive care unit (ICU) admission. Antimicrobial therapy (AMT) is one of the vital management strategies for the treatment of BSIs; it should be chosen appropriately to reduce mortality. ObjectivesThis is the first study to investigate the types of antimicrobial agents administered in the ICU setting and the predictor variables associated with mortality. MethodsThis retrospective study was conducted at King Abdullah University Hospital (KAUH). All hospitalized patients admitted to the ICU and received at least one antimicrobial agent over 3 years period (January 1, 2017, to December 31, 2019) were included in the study. Electronic patients' medical records were used to collect patients' demographic and clinical characteristics, patient general health status, events that occurred during hospitalization, and events after obtaining the blood culture. Descriptive analysis was done to identify the types of antimicrobials used and the distribution of the microorganisms among the study participants. The susceptibility test of the bloodstream culture was checked for each patient. Moreover, crude mortality and its associated factors were investigated. ResultsA total of 1051 patients were enrolled in the study, where 650 patients (61.84%) were treated with three or more antimicrobial agents. The most frequent antimicrobials used were piperacillin/tazobactam followed by teicoplanin, meropenem, and levofloxacin. About half of the patients died within 30-days of BSI, which was associated with several factors including advanced age, presence of co-morbidities, nosocomial infections or healthcare-associated infections, length of ICU stay, respiratory tract infections, receiving vasopressor during the hospital stay, concurrent positive culture other than blood with BSI, receiving combination antimicrobial therapy, those who were complicated with septic shock or renal failure, receiving total parenteral protein (TPN) nutrition, and inappropriate empiric antimicrobial therapy. ConclusionIn conclusion, the administration of the antimicrobials among ICU patients was highly based on a combination of three or more agents covering a broad spectrum of microorganisms. The mortality rate was high among patients which were associated with inappropriate empirical therapy. Therefore, the antimicrobial stewardship (ASP) protocol has to be evaluated in the hospital for ICU patients. Moreover, we suggest recommending that hospital policies should apply the ASP protocol, infection control, implement the antimicrobial de-escalation protocol, and do best controlling on the co-morbid conditions, especially for ages 65 years or more to reduce the mortality rate in the ICU.

Role of the T2Dx magnetic resonance assay in patients with suspected bloodstream infection: a single-centre real-world experience

BackgroundT2Dx was approved by the US Food and Drug Administration for the rapid detection of a modified panel of ESKAPE bacterial species or Candida spp. causing bloodstream infection (BSI).Patients and methodsWe performed a retrospective, observational study from January 1, 2018 to December 31, 2019 of all hospitalised patients with suspected BSI who underwent assessment using T2Dx in addition to standard blood culture (BC). T2-positive patients (cases) were compared to a matched group of patients with BSI documented only by BC (1:2 ratio) to investigate the possible impact of T2Dx on the appropriateness of empirical antimicrobial therapy and 21-day mortality.ResultsIn total, 78 T2Dx-analysed samples (49 patients) were analysed. The T2Dx assay result was positive for18 patients and negative for 31 patients. The concordance rates of the T2Bacteria Panel and T2Candida Panel results with those of standard BC were 74.4% and 91.4%, respectively. In the matched analysis, inappropriate empiric antimicrobial therapy administration was significantly less frequent in cases than in comparators (5.5% vs. 38.8%). The 21-day mortality rate was twofold lower in cases than in comparators (22.2% vs. 44.4%), although the difference was not significant. No other analysed variables were significantly different between the two groups.ConclusionsThis study illustrated that T2Dx might be associated with an increase in the appropriateness of empiric antimicrobial therapy in patients with BSI. Further studies are needed to evaluate whether the T2Dx assay can improve patient outcomes.

48. Association of Rapid Pathogen Identification and Pharmacist Intervention on Time to Optimal Antimicrobial Therapy for Bloodstream Infections at Two Community Hospitals

BackgroundAs many as 1 in 3 patients with bloodstream infections at community hospitals receive inappropriate empiric antimicrobial therapy. Studies have shown that the coupling of real-time intervention with rapid pathogen identification improves patient outcomes and decreases health-system costs at large, tertiary academic centers. The aim of this study was to assess if similar outcomes could be obtained with the implementation of real-time pharmacist intervention to rapid pathogen identification at two smaller, rural community hospitals.MethodsThis was a pre-post implementation study that occurred from September of 2019 to March 2020. This study included patients ≥18 years of age admitted with one positive blood culture. Patients were excluded if they were pregnant, had a polymicrobial blood culture, known culture prior to admission, hospice consulted prior to admission, expired prior to positive blood culture, or transferred to another hospital within 24 hours of a positive blood culture. Endpoints of patients prior to intervention were compared to patients post-implementation. The primary endpoint was time to optimal antimicrobial therapy. Secondary endpoints included time to effective antimicrobial therapy, in-hospital mortality, length of hospital stay, and overall cost of hospitalization.ResultsOf 212 patients screened, 88 patients were included with 44 patients in each group. Both groups were similar in terms of comorbidities, infection source, and causative microbial. No significant difference was seen in the mean time to optimal antimicrobial therapy (27.3±35.5 hr vs 19.4± 30 hr, p=0.265). Patients in the post-implementation group had a significantly higher mean hospitalization cost ($24,638.87± $11,080.91 vs $32,722.07±$13,076.73, p=0.013). There was no significant difference in time to effective antimicrobial therapy, in-hospital mortality, or length of hospital stay.ConclusionThere were no between-group differences in the primary outcome of time to optimal therapy, with a higher mean hospitalization cost after implementation. These results suggest further antimicrobial stewardship interventions are needed, along with larger studies conducted in the community hospital settings.Disclosures All Authors: No reported disclosures

Prevalence, predictors, and consequences of inappropriate empiric antimicrobial therapy for complicated urinary tract and intra-abdominal infections in Winnipeg hospitals

Information on inappropriate empiric antimicrobial therapy (ET) in Canadian hospitals is scarce. All Manitobans 18 years of age and over who were admitted to a hospital in Winnipeg with a complicated urinary tract infection (cUTI) or complicated intra-abdominal infection (cIAI) from January 2006 to December 2014 were eligible for inclusion in this cohort study. The prevalence of inappropriate ET was 11% for cUTI patients and 9% for cIAI patients. The risk of receiving inappropriate ET was higher for older patients (cUTI patients 65 or older had 2-fold increased risk compared to younger patients; odds ratio 2.1, 95% confidence interval 1.3–3.6; this was 1.6 [0.7–3.5] for cIAI patients) and those hospitalized in the previous year: 1.5 (1.0–2.4) in cUTIs and 1.5 (0.6–3.4) in cIAIs. The risk for a hospital stay over 3 weeks was increased for inappropriate ET in cUTI patients, 2.3 (1.4–3.7), but not in cIAI patients, 0.9 (0.4–2.1).

Impact of inappropriate empiric antimicrobial therapy on mortality in pediatric patients with bloodstream infection: a retrospective observational study

Inappropriate empiric antibiotic therapy for bloodstream infection could be associated with mortality in adults. However, data for pediatric patients have been scarce. The purpose of this study was to investigate the impact of an inappropriate empiric antibiotic therapy on mortality in pediatric patients with bloodstream infection. We retrospectively analyzed the data of pediatric patients with consecutive positive blood culture in the university hospital between 2007 and 2016. The association between the use of inappropriate empiric therapy and mortality was investigated. A total of 247 bacteremia events in 223 pediatric patients were analyzed. Overall, 208 (84%) events were hospital acquired and 16 (6%) patients died within 28 days. The most frequent causative microorganisms were Gram-positive bacteria (150 events, 61%), followed by Gram-negative bacteria (90 events, 36%) and Candida spp. (7 events, 3%). Inappropriate empiric antibiotic therapy was prescribed within 48 h in 34 (16%) events. Significantly better 28-day survival rates were obtained in patients that received appropriate empiric antibiotic therapy compared with those who received inappropriate therapy (p = 0.004). Multivariate Cox regression analysis showed that inappropriate empiric antibiotic therapy was an independent prognostic factor of 28-day mortality (hazard ratio, 4.39; 95% confidence interval, 1.48–11.94; p = 0.01), after adjusting for age and McCabe score. Inappropriate empiric antibiotic therapy was associated with poor 28-day mortality in pediatric patients with bloodstream infection. Strategies to increase appropriate selection of empiric antibiotic therapy might be an option for improving survival in pediatric patients with bloodstream infection.

1006. Demographic, Clinical, Microbiological Characteristics and Outcome of Patients Admitted to the Emek Medical Center with Blood Stream Infection Acquired in LTCF: A 5-Year Surveillance

BackgroundResidents from long-term care facilities (LTCF) hospitalized with an acute infectious disease are challenging in terms of diagnosis and treatment, considering atypical clinical presentation are high rate of resistant bacteria,.This study aimed to Characterize patients with LTCF acquired bacteremia (LTCF-B), epidemiology of blood cultures (BC) and potential risk for mortality.MethodsA retrospective study of LTCF residents hospitalized with LTCF-B. Demographic, clinical and laboratory data were collected and analyzed using SPSS 22 and SAS.ResultsOne hundred seventy-seven LTCF residents hospitalized in internal wards were included, mean age 81.6 years, mostly completely dependent, 54.8% were males. Most frequent diagnoses was urinary tract infection (UTI), second by respiratory tract infections. Half were hospitalized during prior 6 months, one-third had a permanent indwelling urinary catheter. On admission, 70% had WBC blood count >10,000 cells/mL. The following pathogens were isolated from BC: Gram-negative enterobacteriaceae (70%): E. coli were 40% and Gram-positive cocci (21%): S. aureus 5.08% (55.5% of them MRSA). Extended-spectrum-β-lactamase (ESBL) producing enterobacteriaceae were in 47.1% BC, clearly document increase during the years, 26% (2010)–63% (2014). Absolute majority of enterobacteriaceae were sensitive to carbapenems and amikacin, half were resistant to gentamycin, second- and third-generation cephalosporins and quinolones. Inappropriate empiric antimicrobial therapy was given to 46.8% of patients with ESBL-producing enterobacteriaceae (P < 0.001). Mortality rates were 21.5% in-hospital and 46.3% day-90 post discharge. Variables associated with mortality: initial diagnosis of skin and soft-tissue infections (SSTI) (OR = 14.44), inappropriate empiric antibiotic (OR = 5.038), high level of urea (OR = 1.017), and nasogastric tube (OR = 4.966). UTI (OR = 0.316) was a protective factor.ConclusionDiagnosis of SSTI, high urea levels, nasogastric tube, and inappropriate empiric antibiotic were associated with in-hospital mortality. The notable increased rate of ESBL-producing enterobacteriaceae should alert physicians to be aware of local microbial resistance profile, especially among LTCFs patients.Disclosures All authors: No reported disclosures.

Sepsis in standard care: patients' characteristics, effectiveness of antimicrobial therapy and patient outcome--a cohort study.

Fast diagnosis and initiation of appropriate antibiotic therapy is pivotal for the survival of sepsis patients. However, most studies on suspected sepsis patients are conducted in the intensive care unit or in the emergency room setting, neglecting the standard care setting. This study evaluated sepsis risk factors, microbiological accurateness of the initial empiric antimicrobial therapy and its effect on hospital mortality in standard care patients. In this prospective observational cohort study, patients with clinically suspected sepsis meeting two or more SIRS criteria were screened on standard care wards. After hospital discharge, occurrence of an infection was assessed according to standardized criteria, and empirical antibiotic therapy was evaluated using antibiograms of recognized pathogens by expert review. Of the 2384 screened patients, 298 fulfilled two or more SIRS criteria. Among these were 28.2 % SIRS patients without infection, 46.3 % non-bacteremic/fungemic sepsis patients and 25.5 % bacteremic/fungemic sepsis patients. Occurrence of a malignant disease and chills were associated with a higher risk of patients having bacteremic/fungemic sepsis, whereas other described risk factors remained insignificant. In total, 91.1 % of suspected sepsis patients received empirical antimicrobial therapy, but 41.1 % of bacteremic sepsis patients received inappropriate therapy. Non-surviving bacteremic sepsis patients received a higher proportion of inappropriate therapy than those who survived (p = 0.022). A significant proportion of bacteremic sepsis patients receive inappropriate empiric antimicrobial therapy. Our results indicate that rapid availability of microbiological results is vital, since inappropriate antimicrobial therapy tended to increase the hospital mortality of sepsis patients.

Characteristics of surgical patients receiving inappropriate empiric antimicrobial therapy.

Inappropriate antibiotics have been observed to result in an increased duration of antibiotic treatment and hospital length of stay, development of multidrug-resistant organisms, and mortality rate compared with appropriate antibiotic treatment. Few studies have evaluated independent risk factors associated with inappropriateness. The purpose of this study was to identify independent predictors of inappropriate, empiric antimicrobial therapy for the treatment of severe sepsis. This was a retrospective analysis of a prospectively maintained database of all surgical/trauma patients admitted to a tertiary care center from 1996 to 2007 and treated for sepsis. "Appropriate" empiric antibiotic treatment was determined by sensitivity testing. Demographics and comorbidities, infection sites, infection organisms, and outcomes between strata were compared. Differences in outcome were estimated using relative risk and 95% confidence intervals for correlated data. A total of 2,855 patients (7,158 infections) were identified. Independent predictors of inappropriate, empiric antimicrobial therapy for the treatment of severe sepsis included site of infection and organism type. Severity of illness, age, medical conditions, and community versus health care-associated infections were not associated with inappropriate therapy. Although inappropriate empiric therapy was associated with a longer length of stay and duration of antimicrobial use, it did not result in higher mortality. Our study observed that inappropriate empiric antibiotic selection is related to site of infection and pathogen. Other clinical variables do not appear to predict inappropriateness of antibiotic treatment. Efforts should be focused on early broad-spectrum therapy and more rapid microbiologic methods. Therapeutic/care management study, level II.

Bloodstream Infections in Community Hospitals in the 21st Century: A Multicenter Cohort Study

BackgroundWhile the majority of healthcare in the US is provided in community hospitals, the epidemiology and treatment of bloodstream infections in this setting is unknown.Methods and FindingsWe undertook this multicenter, retrospective cohort study to 1) describe the epidemiology of bloodstream infections (BSI) in a network of community hospitals and 2) determine risk factors for inappropriate therapy for bloodstream infections in community hospitals. 1,470 patients were identified as having a BSI in 9 community hospitals in the southeastern US from 2003 through 2006. The majority of BSIs were community-onset, healthcare associated (n = 823, 56%); 432 (29%) patients had community-acquired BSI, and 215 (15%) had hospital-onset, healthcare-associated BSI. BSIs due to multidrug-resistant pathogens occurred in 340 patients (23%). Overall, the three most common pathogens were S. aureus (n = 428, 28%), E. coli (n = 359, 24%), coagulase-negative Staphylococci (n = 148, 10%), though type of infecting organism varied by location of acquisition (e.g., community-acquired). Inappropriate empiric antimicrobial therapy was given to 542 (38%) patients. Proportions of inappropriate therapy varied by hospital (median = 33%, range 21–71%). Multivariate logistic regression identified the following factors independently associated with failure to receive appropriate empiric antimicrobial therapy: hospital where the patient received care (p<0.001), assistance with ≥3 ADLs (p = 0.005), Charlson score (p = 0.05), community-onset, healthcare-associated infection (p = 0.01), and hospital-onset, healthcare-associated infection (p = 0.02). Important interaction was observed between Charlson score and location of acquisition.ConclusionsOur large, multicenter study provides the most complete picture of BSIs in community hospitals in the US to date. The epidemiology of BSIs in community hospitals has changed: community-onset, healthcare-associated BSI is most common, S. aureus is the most common cause, and 1 of 3 patients with a BSI receives inappropriate empiric antimicrobial therapy. Our data suggest that appropriateness of empiric antimicrobial therapy is an important and needed performance metric for physicians and hospital stewardship programs in community hospitals.

Antimicrobial therapeutic determinants of outcomes from septic shock among patients with cirrhosis

It is unclear whether practice-related aspects of antimicrobial therapy contribute to the high mortality from septic shock among patients with cirrhosis. We examined the relationship between aspects of initial empiric antimicrobial therapy and mortality in patients with cirrhosis and septic shock. This was a nested cohort study within a large retrospective database of septic shock from 28 medical centers in Canada, the United States, and Saudi Arabia by the Cooperative Antimicrobial Therapy of Septic Shock Database Research Group between 1996 and 2008. We examined the impact of initial empiric antimicrobial therapeutic variables on the hospital mortality of patients with cirrhosis and septic shock. Among 635 patients with cirrhosis and septic shock, the hospital mortality was 75.6%. Inappropriate initial empiric antimicrobial therapy was administered in 155 (24.4%) patients. The median time to appropriate antimicrobial administration was 7.3 hours (interquartile range, 3.2-18.3 hours). The use of inappropriate initial antimicrobials was associated with increased mortality (adjusted odds ratio [aOR], 9.5; 95% confidence interval [CI], 4.3-20.7], as was the delay in appropriate antimicrobials (aOR for each 1 hour increase, 1.1; 95% CI, 1.1-1.2). Among patients with eligible bacterial septic shock, a single rather than two or more appropriate antimicrobials was used in 226 (72.9%) patients and was also associated with higher mortality (aOR, 1.8; 95% CI, 1.0-3.3). These findings were consistent across various clinically relevant subgroups. Conclusion: In patients with cirrhosis and septic shock, inappropriate and delayed appropriate initial empiric antimicrobial therapy is associated with increased mortality. Monotherapy of bacterial septic shock is also associated with increased mortality. The process of selection and implementation of empiric antimicrobial therapy in this high-risk group should be restructured. (Hepatology 2012;56:2305–2315)

Impact of inappropriate empiric antimicrobial therapy on mortality of septic patients with bacteremia: a retrospective study

Impact of inappropriate empiric antimicrobial therapy on mortality of septic patients with bacteremia: a retrospective study

Impact of Inappropriate Empiric Antimicrobial Therapy on Mortality of Septic Patients with Bacteremia: A Retrospective Study

Background. Inappropriate empiric antimicrobials could be a major cause of unfavorable mortality rates in co-morbid patients. This study aimed to assess the prevalence and impact of first-dose and 24-hour inappropriate antimicrobials on mortality rates of bacteremic septic patients. Methods. A retrospective cohort study was employed. Case record forms of patients diagnosed as sepsis, severe sepsis, or septic shock with positive hemoculture during 2009 were retrieved from the medical wards, Siriraj Hospital. Demographic data, antimicrobial use, types of bacteria isolated from blood and susceptibilities, patients' comorbidities, 28-day and overall mortality rates were collected and analyzed. Results. There were 229 cases, mean age (SD) of 63.5 (17.2) years and mean (SD) APACHE II score of 24.7 (6.8). The prevalence of first-dose and 24-hour inappropriate antimicrobials was 29.7% and 25.3%, respectively. The 28-day and overall mortality rates between first-dose inappropriate and appropriate antimicrobial were 67.6% versus 60.2% (P = 0.301) and 75.0% versus 68.3% (P = 0.345), consequently. Patients with septic shock and inappropriate first-dose antimicrobials significantly had higher 28-day mortality rate (61.6% versus 41.9%; P = 0.017). Conclusion. Higher mortality rates in bacteremic septic patients were substantially associated with inappropriate first-dose antimicrobials and 3-hour delayed antimicrobial administration after sepsis diagnosis.

Impact of inappropriate empiric antimicrobial therapy on outcome in Pseudomonas aeruginosa bacteraemia: a stratified analysis according to sites of infection

The purpose of this study was to evaluate the impact of inappropriate empiric antimicrobial therapy on the outcome of Pseudomonas aeruginosa bacteraemia according to the primary infection site. A retrospective cohort study including 202 patients with P. aeruginosa bacteraemia was performed. High-risk sites of infection were defined as the lung, intra-abdominal non-hepatobiliary tract or unknown source. Of the 202 patients with P. aeruginosa bacteraemia, 80 (39.6%) had received inappropriate empiric antimicrobial therapy. No significant difference in the 30-day mortality rate was found between the inappropriate therapy group and the appropriate therapy group (19/80 [23.8%] vs. 32/122 [26.2%], P = 0.692). Patients with pneumonia or non-hepatobiliary tract intra-abdominal infection showed significant association with high mortality, while those with urinary tract or hepatobiliary tract infection showed negative associations with mortality. In the subgroup analysis including 98 patients with high-risk sites of infection, the mortality rate of the inappropriate therapy group was significantly higher than that of the appropriate therapy group (14/26 [53.8%] vs. 23/72 [31.9%], P = 0.035). Inappropriate empiric antimicrobial therapy was also found to be one of the independent risk factors for mortality in patients with high-risk sites of infection (odds ratio [OR] 8.69; 95% confidence interval [CI] 1.86-40.59), along with renal disease, corticosteroid use, polymicrobial infection and higher Pitt bacteraemia score. Inappropriate empiric antimicrobial therapy adversely affected the outcome of P. aeruginosa bacteraemia in patients with high-risk sites of infection. Our data suggest that the impact of inappropriate antimicrobial therapy on the outcome of P. aeruginosa bacteraemia may be dependent on the primary site of infection.

Impact of Empiric Antimicrobial Therapy on Outcomes in Patients with Escherichia coli and Klebsiella pneumoniae Bacteremia: A Cohort Study

BackgroundIt is unclear whether appropriate empiric antimicrobial therapy improves outcomes in patients with bacteremia due to Escherichia coli or Klebsiella. The objective of this study is to assess the impact of appropriate empiric antimicrobial therapy on in-hospital mortality and post-infection length of stay in patients with Escherichia coli or Klebsiella bacteremia while adjusting for important confounding variables.MethodsWe performed a retrospective cohort study of adult patients with a positive blood culture for E. coli or Klebsiella between January 1, 2001 and June 8, 2005 and compared in-hospital mortality and post-infection length of stay between subjects who received appropriate and inappropriate empiric antimicrobial therapy. Empiric therapy was defined as the receipt of an antimicrobial agent between 8 hours before and 24 hours after the index blood culture was drawn and was considered appropriate if it included antimicrobials to which the specific isolate displayed in vitro susceptibility. Data were collected electronically and through chart review. Survival analysis was used to statistically assess the association between empiric antimicrobial therapy and outcome (mortality or length of stay). Multivariable Cox proportional hazards models were used to calculate hazard ratios (HR) and 95% confidence intervals (CI).ResultsAmong 416 episodes of bacteremia, 305 (73.3%) patients received appropriate empiric antimicrobial therapy. Seventy-one (17%) patients died before discharge from the hospital. The receipt of appropriate antimicrobial agents was more common in hospital survivors than in those who died (p = 0.04). After controlling for confounding variables, there was no association between the receipt of appropriate empiric antimicrobial therapy and in-hospital mortality (HR, 1.03; 95% CI, 0.60 to 1.78). The median post-infection length of stay was 7 days. The receipt of appropriate antimicrobial agents was not associated with shortened post-infection length of stay, even after controlling for confounding (HR, 1.11; 95% CI 0.86 to 1.44).ConclusionAppropriate empiric antimicrobial therapy for E. coli and Klebsiella bacteremia is not associated with lower in-hospital mortality or shortened post-infection length of stay. This suggests that the choice of empiric antimicrobial agents may not improve outcomes and also provides data to support a randomized trial to test the hypothesis that use (and overuse) of broad-spectrum antibiotics prior to the availability of culture results is not warranted.

The Efficacy and Safety of Tigecycline for the Treatment of Complicated Intra-Adominal Infections - The European Experience

The polymicrobial nature of complicated intra-abdominal infections makes these infections particularly challenging to treat. The initial selection of antimicrobial therapy is therefore extremely important. Inappropriate empiric antimicrobial therapy has been shown to delay clinical resolution, increase length of hospital stay, and increase the risk of mortality. In addition, the increasing frequency with which resistant isolates (e.g., extended spectrum beta-lactamases [ESBLs]) are recovered from patients mandates that empiric antimicrobial therapy covers these difficult-to-treat organisms.Here, we assessed the efficacy of a new antimicrobial agent, tigecycline. This is a combined analysis of data from the European sites that participated in two Phase III, double-blind trials to evaluate the efficacy and safety of tigecycline, versus that of imipenem/cilastatin, in adults with complicated intra-abdominal infections. Patients received either tigecycline (initial dose of 100 mg, followed by 50 mg intravenously every 12 hours) or imipenem/cilastatin (500/500 mg intravenously every 6 hours) for 5-14 days. The primary end point was the clinical response at the test-of-cure visit (12-44 days after therapy) in the co-primary microbiologically evaluable (ME) and microbiological modified intent-to-treat (m-mITT) populations. For the ME group, clinical cure rates at the test-of-cure visit were 92.4% (219/237) for tigecycline versus 88.8% (198/223) for imipenem/cilastatin (95% CI = −2.2, 9.4). Clinical cure rates for the m-mITT populations were 87.3% (247/283) for tigecycline versus 83.5% (228/273) for imipenem/cilastatin (95% CI = −2.5, 10.0) at the test-of-cure visit. Pretherapy in vitro activity against baseline isolates for tigecycline and imipenem/cilastatin were also determined. The mean MIC90 for tigecycline against the most commonly isolated aerobes and anaerobes was >2.0 μg/mL. No pretherapy isolates displayed resistance to tigecycline based on the breakpoints used. Bacterial susceptibilities to tigecycline appeared to be consistent with clinical responses. Most commonly reported treatment emergent adverse events for tigecycline and imipenem/cilastatin were nausea (14.7% and 11.8%, respectively, p = 0.267) and vomiting (10.7% and 7.3%, respectively p = 0.146). This combined analysis demonstrates that tigecycline is safe and effective for the treatment of complicated intra-abdominal infections, and reflects the findings of the global population.

The empiric treatment of nosocomial intra-abdominal infections

The treatment of complicated intra-abdominal infections continues to challenge physicians, primarily because of the polymicrobial nature of these infections coupled with the high risk of complications and even death among the more severe patients. The initial selection of antimicrobial therapy for treatment of nosocomial intraabdominal infections is extremely important because an association has been shown between inappropriate empiric antimicrobial therapy and delayed clinical resolution, increased length of hospital stay, and an increased risk of mortality. Moreover, it is becoming more frequent for isolates recovered from patients to possess multiple resistance factors (e.g., extended-spectrum beta-lactamases [ESBLs], vancomycin-resistant enterococci [VRE]). Therefore, when selecting empiric antimicrobial therapy, the physician must consider the likelihood of encountering one of these difficult-to-treat isolates and select an agent or agents with anticipated activity against such organisms. Here, we discuss the merits and limitations of empiric therapy for nosocomial intra-abdominal infections, review the current guidelines for treatment, and discuss the therapeutic options currently available.