Appropriateness Of Empirical Therapy Research Articles

Improving Empiric Antibiotic Therapy Among Cancer Patients With Acute Cholangitis

Abstract Introduction Acute cholangitis (AC) is a hepatobiliary infection that requires prompt antibiotic therapy. Providers have to rely on empiric antibiotic guidelines, before receiving culture results. These antibiotic guidelines require routine surveillance of the biliary microbial flora and resistance patterns found in cultures to increase accuracy and appropriateness of empiric therapy. This is particularly essential in cancer patients who are more likely to be exposed to various antibiotics, potentially creating unique bactobilia, and fungobilia selection pressures that are different from the general patient population and require empiric therapy to halt AC progression to septicemia, shock, or mortality. This unique population is poorly researched and primary literature is relatively scarce. Methodology A retrospective chart review was performed to identify all patients between the age of 18 and 85 years who met the criteria for positive biliary culture and were treated for AC using empiric antibiotic treatment at the H. Lee Moffitt Cancer Center and Research Institute from January 2012 to January 2019. The patient information and laboratory results were analyzed to identify the microbial spectrum and drug resistance in bile cultures of cancer patients. Aim The aim of the study is to review the microbial patterns and characteristics of AC in immunocompromised patients with cancer. Results Pancreatic carcinomas and cholangiocarcinoma were most prevalent malignancies among patients. Although most bile cultures were polymicrobial, further analysis indicated Enterococcus species. Streptococcus species, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Candida albicans were the most common isolates. Conclusions Cholangitis in cancer patients develops because of cholestasis from cancer obstructing the biliary flow mostly because of pancreatic cancer, cholangiocarcinoma, and metastatic cancer to the porta hepatis. Empiric antibiotic therapy should include broad-spectrum coverage for usual enteric flora.

The diagnostic yield and safety of sputum induction in suspected pulmonary tuberculosis: The experience of a single tertiary care center in Saudi Arabia.

Sputum smear microscopy examination and culture for tuberculosis (TB) remain a fundamental tool of diagnosis but may be negative up to 50% case of active pulmonary TB. Bronchoscopy to obtain sputum is invasive and not readily available. Alternative methods of obtaining sputum specimens are crucial in suspected pulmonary TB cases who are unable to expectorate. In this context, it may be beneficial to stimulate sputum production by administering a mist of hypertonic saline produced by ultrasonic nebulization. The aims of the study are to describe the experience of a tertiary center in Saudi Arabia with sputum induction (SI) for the investigation of patients suspected to have sputum scare TB. A retrospective cohort study was performed. All patients suspected of sputum scare TB and investigated with SI were included. Standard descriptive statistics were used. Categorical data presented as frequency were compared using the Chi square test. Continuous data presented as mean ± standard deviation were compared using Student's t test. Sensitivity, specificity, and predictive values were calculated. Of 252 patients with suspected TB who underwent SI, 78 (31%) were ultimately diagnosed to have TB. Culture of induced sputum confirmed the diagnosis of TB in 44 (56.4%) of these patients. However, the diagnosis of TB would have been missed in 13.5% of the cohort if no further investigations were done. The incidence of complications was low. No patients required hospitalization or specialist intervention. SI is safe well tolerated and inexpensive. It may reduce the need for bronchoscopy in patients with suspected sputum scare TB. However, around 20% of TB can be missed by SI unless further investigations are performed. Hence, patients suspected to have sputum scare TB in whom the risk of bronchoscopy is high, a clinical decision on the appropriateness of empirical therapy is often required.

Mortality impact of empirical antimicrobial therapy inESBL- and AmpC-producing Enterobacteriaceae bacteremia in an Australian tertiary hospital.

Treatment of ESBL- and AmpC-producing Enterobacteriaceae bacteremia is often complicated by lack of appropriate antibiotics. We aimed to determine the predictors of mortality and impact of empirical antibiotics. A retrospective observational study was performed on consecutive adult cases of ESBL and AmpC bacteremia at the Alfred Hospital from 2014 through April 2018. Among 110 patients with ESBL (88.2%) and AmpC (14.5%) bacteremia episodes, 96.4% had comorbidities such as hematological malignancy (30%). Approximately 45% were on immunosuppressive drugs, while 69% had recent antibiotic exposure. Over 84% of bacteremias were hospital acquired or healthcare associated. Urinary tract was the main source of infection (40%) with E. coli being the commonest organism (66.4%). The isolates were least resistant to gentamicin (21.8%), which was often appropriately used in empirical therapy. About 34% of patients presented with severe sepsis or shock. The 30-day mortality rate was 20% with no correlation with inappropriate empirical antibiotics (52%). There was no significant mortality difference between carbapenem use in empirical and definitive therapy. Respiratory source [OR 11.77, 95% CI 1.30-106.85; p=0.03], severe sepsis or shock [OR 5.17, 95% CI 1.37-19.55; p=0.02] and inappropriate definitive therapy [OR 27.93, 95%CI 3.69-211.35; p=0.001] were independent predictors for mortality. The choice and appropriateness of empirical therapy were not associated with mortality in ESBL and AmpC bacteremia. Prudent use of carbapenem is reasonable with gentamicin as alternative. Emphasis should be on prompt resuscitation in severe sepsis and early detection of ESBL and AmpC to facilitate appropriate switch to definitive therapy.

Validation of an Antimicrobial Stewardship Driven Verigene® Blood-Culture Gram-Negative Treatment Algorithm to Improve Appropriateness of Antibiotics

BackgroundGram-negative bacteremia (GNB) is associated with significant morbidity and mortality, emphasizing the need for timely, effective antimicrobial therapy. In comparison to conventional diagnostic methods, Verigene® Blood-Culture Gram-Negative (VBC-GN) is a microarray rapid diagnostic test that identifies eight target GN organisms and six genetic resistance determinants. This study examined the potential clinical impact of VBC-GN coupled with a proposed antimicrobial stewardship (AMS)-derived treatment algorithm to guide timely, appropriate antimicrobial therapy in GNB.MethodsRetrospective, single-center, study of adult patients (≥ 18 years) with GNB at University of Maryland Medical Center (UMMC) from September 2015 – May 2016. Patient clinical characteristics, co-morbidities, and antimicrobials administered were collected. Appropriateness of antimicrobial therapy was by in vitro susceptibility. Appropriateness of actual empiric antimicrobials received as standard care were compared with theoretical antimicrobials as guided by the UMMC AMS treatment algorithm. Two investigators (KCC and ELH) independently evaluated appropriateness of empiric and algorithm antimicrobial recommendations.Results188 patients (median age 57.0 (IQR 46.5 – 65.0) years) with GNB were included and 143 (76.1%) were positive for target GN organisms. Eight (4.3%) cases were GN polymicrobial, 8 (4.3%) were CTX-M positive. E. coli was the most common target GN organism (30.3%), and genitourinary was the most common source (29.3%). There was a good level of agreement between reviewers regarding appropriateness of empiric therapy (Kappa = 0.735) and algorithm recommendations (Kappa = 0.855). Overall, the proposed algorithm would have resulted in 88.4% of cases receiving appropriate antimicrobial therapy vs 78.1% actual empiric antimicrobials (P = 0.014). The AMS treatment algorithm would have resulted in 14.4% appropriate de-escalation, 4.8% inappropriate de-escalation, 5.3% appropriate escalation, and 16.0% unnecessary escalation.ConclusionProposed antibiotics by AMS-derived treatment algorithm applied in conjunction with rapid diagnostic testing would result in a significantly higher proportion of patients receiving appropriate antimicrobial therapy vs. standard care.Disclosures J. K. Johnson, Nanosphere: Grant Investigator, Grant recipient

Risk Factors for and Outcomes of Bacteremia Caused by Extended-Spectrum ß-Lactamase-Producing Escherichia coli and Klebsiella Species at a Canadian Tertiary Care Hospital.

Antimicrobial resistance due to production of extended-spectrum ß-lactamases by Escherichia coli and Klebsiella species (ESBL-EK) is concerning. Previous studies have shown that bacteremia due to ESBL-producing organisms is associated with increases in length of stay and/or mortality rate. Rates of infection by ESBL-EK vary worldwide, and regional differences in the prevalence of risk factors are likely. Few Canadian studies assessing risk factors for ESBL-EK infections or the outcomes of empiric therapy have been published. To determine risk factors for and patient outcomes associated with ESBL-EK bacteremia. The appropriateness of empiric antibiotic therapy and the effect of inappropriate empiric therapy on these outcomes were also examined. In a retrospective, 1:1 case-control study conducted in a tertiary care hospital between 2005 and 2010, data for 40 patients with ESBL-EK bacteremia were compared with data for 40 patients who had non-ESBL-EK bacteremia. Of all variables tested, only antibiotic use within the previous 3 months was found to be an independent risk factor for acquisition of ESBL-EK bacteremia (odds ratio 5.2, 95% confidence interval 1.6-16.9). A greater proportion of patients with non-ESBL-EK bacteremia received appropriate empiric therapy (88% [35/40] versus 15% [6/40], p < 0.001). Time to appropriate therapy was longer for those with ESBL-EK bacteremia (2.42 days versus 0.17 day, p < 0.001). Patient outcomes, including length of stay in hospital, admission to the intensive care unit (ICU), length of stay in the ICU (if applicable), and in-hospital mortality were not affected by the presence of ESBL-EK or the appropriateness of empiric therapy. Previous antibiotic use was a significant, independent risk factor for acquiring ESBL-EK. Thus, prior antibiotic use is an important consideration in the selection of empiric antibiotic therapy and should increase the concern for resistant pathogens.

Klebsiella pneumoniae bloodstream infection: epidemiology and impact of inappropriate empirical therapy.

Multidrug resistance associated with extended-spectrum beta-lactamase (ESBL) and Klebsiella pneumoniae carbapenemase (KPC) among K. pneumoniae is endemic in southern Europe. We retrospectively analyzed the impact of resistance on the appropriateness of empirical therapy and treatment outcomes of K. pneumoniae bloodstream infections (BSIs) during a 2-year period at a 1420-bed tertiary-care teaching hospital in northern Italy. We identified 217 unique patient BSIs, including 92 (42%) KPC-positive, 49 (23%) ESBL-positive, and 1 (0.5%) metallo-beta-lactamase-positive isolates. Adequate empirical therapy was administered in 74% of infections caused by non-ESBL non-KPC strains, versus 33% of ESBL and 23% of KPC cases (p < 0.0001). To clarify the impact of resistance on BSI treatment outcomes, we compared several different models comprised of non-antibiotic treatment-related factors predictive of patients’ 30-day survival status. Acute Physiology and Chronic Health Evaluation (APACHE) II score determined at the time of positive blood culture was superior to other investigated models, correctly predicting survival status in 83% of the study cohort. In multivariate analysis accounting for APACHE II, receipt of inadequate empirical therapy was associated with nearly a twofold higher rate of death (adjusted hazard ratio 1.9, 95% confidence interval 1.1–3.4; p = 0.02). Multidrug-resistant K. pneumoniae accounted for two-thirds of all K. pneumoniae BSIs, high rates of inappropriate empirical therapy, and twofold higher rates of patient death irrespective of underlying illness.

Empiric antibiotic choices for community-acquired biliary tract infections

SummaryBackgroundThe study was conducted to reveal the most appropriate empiric antibiotics for the treatment of community‐acquired biliary tract infections (CA‐BTI) at a regional hospital in Taiwan.MethodsThe study was performed between October 1, 2010 and October 31, 2012. All positive bile culture results of presumptive community‐acquired origins were collected. The associated etiologic microorganisms and their antimicrobial susceptibilities were analyzed. The appropriateness of empiric therapy (defined as the effectiveness of the antibiotics against the etiologic agents) and the subsequent treatment response were examined through the review of medical records.ResultsA total of 115 patients (cholecystitis, 83 cases, 72.2%; cholangitis, 32 cases, 27.8%) and 189 isolates (136 Gram‐negative bacilli, 37 Gram‐positive cocci, and 16 anaerobes) were analyzed. The most frequent pathogens were Escherichia coli (n = 69, 36.5%), Klebsiella spp. (n = 37, 19.6%), enterococci (n = 29, 15.3%), and Bacteroides spp. (n = 11, 5.8%). Penicillin resistance (5.4%) was low in Gram‐positive cocci, whereas higher resistance (&gt;20%) to cefazolin, cefuroxime, and ampicillin–sulbactam was found in Gram‐negative bacilli. Anaerobes also demonstrated high resistance to clindamycin (37.5%) but less to metronidazole (12.5%). Appropriate empiric therapy was found in 92 (80%) cases, and among them, 83 (90.2%) were treated successfully. The treatment success rate (69.6%) was significantly lower among the remaining 23 cases with inappropriate empiric therapy (16 of 23 vs. 83 of 92, p &lt; 0.05). A high treatment success rate (97.2%) was observed among cases empirically treated with ceftriaxone plus metronidazole.ConclusionThe combination of ceftriaxone plus metronidazole appears to be the most appropriate empiric antibiotics for the treatment of CA‐BTI at this hospital. Because different hospitals may encounter microorganisms of different antimicrobial susceptibilities, similar approaches may be followed by other hospitals where appropriate empiric therapy has not yet been established for the treatment of CA‐BTI.

Time to effective antibiotic administration in adult patients with septic shock: A descriptive analysis

To determine the median time to antibiotic administration following the onset of septic shock at our institution as well as the appropriateness of empiric therapy, sources of delay in antibiotic administration and the effect of delays on survival. Retrospective health record review of 55 patients with septic shock admitted to the intensive care unit (ICU) between July 1, 2008 and December 31, 2009. Nine-bed adult medical-surgical ICU within a 300-bed community acute care hospital. Median time to antibiotic administration, appropriateness of empiric therapy, sources of delay in antibiotic administration. The median (min,max) time to the initiation of antibiotics was determined to be 1.7 (0,31) hours. Only 34% (19/55) of patients received antibiotics within the recommended one hour. Empiric antibiotic therapy was determined to be appropriate in 91% (50/55) of patients. The median (min,max) time to administration of effective antibiotic therapy tended to be faster in the emergency room [1.1 (0,16) hours] compared to the ICU [2.3 (0,13)]. The median time to antibiotic administration at our institution following the onset of septic shock was longer than the evidence-based guideline recommendations of within one hour.

Empiric therapy for treatment of infection and the influence of antibiotic guidelines on outcomes

AbstractThe appropriateness of empiric therapy, how closely prescribers adhered to hospital guidelines for use of antimicrobial drugs and how relevant these guidelines proved in providing cover for the infecting pathogen were assessed from a retrospective survey of culture and sensitivity reports issued during a one-month period in a district general hospital. Blood, stool, pus, sputum and mid-stream urine specimens were reviewed. Urine specimens from a fundholding general practice unit were also included. Catheter specimens of urine and specimens from other body sites were excluded. Of 290 specimens sent for culture, 99 (34 per cent) were positive. One hundred patients, of whom 54 (19 per cent of the total) were subsequently demonstrated to have a positive culture, had been treated empirically. In 38 per cent of cases the pre-report empiric treatment was considered appropriate for the isolated pathogen, while 46 per cent of patients had negative cultures and 16 per cent had positive cultures but had been given unsuitable antibiotics. In hospitalised patients, 73 per cent of antibiotic treatments were prescribed according to hospital guidelines, although this was the case for only 45 per cent of community-based patients. Hospital guidelines were a relevant and useful aid to rational prescribing in that 75 per cent of organisms isolated were sensitive to guideline antibiotics. The guidelines were least appropriate for urine specimens from hospital. This reflects the range of organisms encountered and the emergence of resistant strains, reinforcing the need for regular updating and amending of prescribing recommendations.

Independent Predictors for Mortality in Patients with Positive Stenotrophomonas maltophilia Cultures

Stenotrophomonas maltophilia is an emerging pathogen in nosocomial infections that may result in high mortality. S. maltophilia often present as part of a polymicrobial culture and it is not well established when treatment is indicated. We aimed to identify predictors of mortality in patients with positive cultures of S. maltophilia. A retrospective cohort study in a tertiary care medical centre was performed in 150 adult patients with positive cultures of S. maltophilia. Patients' demographics, underlying diseases, severity of illness, length of hospitalisation, prior antibiotic exposure, number/types of indwelling catheters, culture sites, and appropriateness of empiric therapy were collected. Logistic regression was used to determine the independent risk factor(s) for infection-attributed mortality. Ninety-nine males and 51 females were studied. The mean (SD) age and APACHE II score of the patients were 61.9 (16.0) and 14.0 (6.1), respectively. The respiratory tract was the most frequent site (55.3%) where S. maltophilia was isolated. Infection-attributed mortality was observed in 22 of the 150 patients (14.7 %). Admission to ICU [Odds ratio (OR), 3.767; 95% confidence interval (CI), 1.277-11.116, P = 0.016], and delayed effective treatment (OR, 18.684; 95% CI, 4.050-86.188; P <0.001) were identified as independent risk factors for mortality. Predictors of mortality in patients with positive cultures of S. maltophilia were identified, which may guide clinicians in patient assessment and devising therapeutic decisions. Further studies are needed to validate our results.

Antibiothérapie des états infectieux graves

Severe sepsis, which is related to a high mortality rate, requires a very specific antibiotic strategy, which must be adapted to each case. The appropriateness of empiric therapy is based on the delay before administration of the molecule, the bacterial resistance profile, and the kinetic and/or dynamic properties of the available antibiotics.

PGI14: HOW IMPORTANT IS APPROPRIATE EMPIRICAL ANTIBIOTIC TREATMENT FOR INTRA-ABDOMINAL INFECTIONS?

OBJECTIVES: To assess the association between hospital costs and the appropriateness of empirical antibiotic treatment for community-acquired intra-abdominal infection. METHODS: Patients were identified from hospital discharges from three hospitals for 1993 to 1997. Medical records were obtained to validate the diagnosis and obtain details of antibiotic therapy and its outcome. Valid cases had macroscopic evidence of intra-abdominal infection at operation, therefore all cases had surgical control of infection in addition to antimicrobial therapy. Appropriateness of empirical therapy was assessed from the results of in-vitro sensitivity tests (culture positive cases) and compliance with local antibiotic policies (culture negative cases). RESULTS: We identified 294 valid cases of intra-abdominal infection of whom 162 (55%) were culture positive. Appropriate antibiotic treatment was associated with significantly shorter length of stay and lower investigation costs for patients with positive cultures but not for patients with negative cultures or no test/result (data not shown). Culture +ve cases, appropriate (n = 129) vs inappropriate (n = 33): mean length of stay 12 vs 22 days, p = 0.0007 boot strap t test, mean investigation cost £250 vs £409 p = 0.04, mean antibiotic cost £138 vs £128 p = 0.9. A log transformed linear regression analysis was carried out on the cost data for the culture positive cases adjusting for five independent variables. Inappropriate antibiotics, increasing age and a higher number of comorbidities and previous admissions were significantly associated with increased cost of hospital stay but not gender. This model accounted for 34% of the variance in cost of hospital stay. For the cost of investigations inappropriate treatment, increasing age and number of comorbidities were all significant predictors accounting for 26% of variance in costs. Number of comorbidities was the only variable significantly associated with the cost of antibiotics. CONCLUSIONS: Appropriate empirical antibiotic treatment of patients with culture positive intra-abdominal infection is strongly associated with length of stay and hospital costs.