Inappropriate Empirical Antibiotic Therapy Research Articles

Health Care–Associated Pneumonia Requiring Hospital Admission

Health care-associated pneumonia (HCAP) has been proposed as a new category of respiratory infection. However, limited data exist to validate this entity. We aimed to ascertain the epidemiology, causative organisms, antibiotic susceptibilities, and outcomes of and empirical antibiotic therapy for HCAP requiring hospitalization. Observational analysis of a prospective cohort of nonseverely immunosuppressed hospitalized adults with pneumonia. Patients who had recent contact with the health care system through nursing homes, home health care programs, hemodialysis clinics, or prior hospitalization were considered to have HCAP. Of 727 cases of pneumonia, 126 (17.3%) were HCAP and 601 (82.7%) were community acquired. Compared with patients with community-acquired pneumonia, patients with HCAP were older (mean age, 69.5 vs 63.7 years; P < .001), had greater comorbidity (95.2% vs 74.7%; P < .001), and were more commonly classified into high-risk pneumonia severity index classes (67.5% vs 48.8%; P < .001). The most common causative organism was Streptococcus pneumoniae in both groups (27.8% vs 33.9%). Drug-resistant pneumococci were more frequently encountered in cases of HCAP. Legionella pneumophila was less common in patients with HCAP (2.4% vs 8.8%; P = .01). Aspiration pneumonia (20.6% vs 3.0%; P < .001), Haemophilus influenzae (11.9% vs 6.0%; P = .02), Staphylococcus aureus (2.4% vs 0%; P = .005), and gram-negative bacilli (4.0% vs 1.0%; P = .03) were more frequent in HCAP. Patients with HCAP more frequently received an initial inappropriate empirical antibiotic therapy (5.6% vs 2.0%; P = .03). The overall case-fatality rate (< 30 days) was higher in patients with HCAP (10.3% vs 4.3%; P = .007). At present, a substantial number of patients initially seen with pneumonia in the emergency department have HCAP. These patients require a targeted approach when selecting empirical antibiotic therapy.

Consequences of inappropriate initial empiric parenteral antibiotic therapy among patients with community-acquired intra-abdominal infections in Spain

To assess the association between inappropriate antibiotic therapy and clinical outcomes for complicated community-acquired intra-abdominal infections in Spain, patient records from October 1998 to August 2002 in 24 hospitals were reviewed. Initial empiric therapy was classified appropriate if all isolates were sensitive to at least 1 of the antibiotics administered. Multivariate analyses were performed to assess associations between appropriateness of therapy and patient outcomes. Healthcare resource use was measured as hospital length of stay (LOS) and d on intravenous antibiotic therapy. A total of 425 patients were included. Of these, 387 (91%) received appropriate initial empiric therapy. Patients on inappropriate therapy were less likely to have clinical success (79% vs 26%, p<0.001), more likely to require additional antibiotic therapy (40% vs 7%, p<0.01) and more likely to be re-hospitalized within 30 d of discharge (18% vs 3%, p<0.01). Multivariate analyses also showed that inappropriate therapy was associated with an almost 16% increase in LOS (p<0.05) and 26% in d of intravenous antibiotic therapy compared with appropriate therapy (p<0.05). Inappropriate initial antibiotic therapy was associated with a significantly higher proportion of unsuccessful patient outcomes (including death, re-operation, re-hospitalization or additional parental antibiotic therapies), increased length of stay and length on therapy.

Importance of appropriateness of empiric antibiotic therapy on clinical outcomes in intra-abdominal infections

The objective of this study is to describe the frequency of inappropriate empirical antibiotic therapy in secondary intra-abdominal infection and to identify the possible relationship between inappropriateness and some clinical outcomes. A retrospective descriptive multicenter study was conducted using hospital secondary databases developed at two university hospitals located in northeast Spain. Participants were patients 18 years of age or older who were diagnosed with community-acquired intra-abdominal infections between January 1, 1998, and December 31, 2000, identified through computerized patient records using ICD-9 codes. Appropriateness of empirical treatment was defined according to the recommendations of the literature. The clinical outcome of each patient was classified as one of the following: (i) resolved with initial therapy, (ii) required second-line antibiotics, (iii) required re-operation, or (iv) in-hospital death. The Fisher's exact test or the Chi-squared test for categorical variables and the t-test or Mann-Whitney test for continuous variables were used for comparing groups. Conditional logistic and linear regression analyses were also applied. Of 376 cases, 51 cases (13.6 percent, 95 percent confidence interval, 10-17 percent) received inappropriate empirical antibiotic therapy according to the scientific literature. Inappropriate initial empirical treatment was significantly associated with the need for a second line of antibiotics (p < .001), although not with re-operation, mortality, or length of hospitalization. Approximately 14 percent of the patients received inappropriate empirical antibiotic treatment. Worse clinical outcomes consistently were observed in the group of patients receiving inappropriate empirical treatment. The appropriateness of antibiotic treatment for a given infection, in light of the availability of clearly defined clinical guidelines is an easily evaluated aspect of the quality of care.

Implications of COPD in patients admitted to the intensive care unit by community-acquired pneumonia

The mortality rate of chronic obstructive pulmonary disease (COPD) patients with community-acquired pneumonia (CAP) is reported to be low. However, studies carried out to date have included <20% of critically ill patients. The current authors performed a secondary analysis of a prospective study evaluating 428 immunocompetent patients admitted to the intensive care unit (ICU) for severe CAP. In total, 176 COPD patients were compared with 252 non-COPD patients. In COPD patients, ICU mortality (odds ratio (OR) 1.58; 95% confidence interval (CI) 1.01-1.43) and mechanical ventilation (OR 2.78; 95% CI 1.63-4.74) rates were higher than in non-COPD patients. The ICU mortality was 39% for COPD patients initially intubated and 50% for those who failed noninvasive ventilation. The proportion of patients who were males, aged >/=70 yrs, smokers and who had chronic heart disease or Pseudomonas aeruginosa were higher in COPD patients. Inappropriate empirical antibiotic therapy was associated with higher mortality (OR 3.8; 95% CI 1.19-12.6). ICU mortality in COPD patients with adequate therapy was associated with bilateral pneumonia (OR 2.32; 95% CI 1.18-4.53) and shock (OR 3.53; 95% CI 1.31-9.71). In conclusion, chronic obstructive pulmonary disease patients hospitalised with community-acquired pneumonia in the intensive care unit had higher mortality and need of mechanical ventilation when compared with patients without chronic obstructive pulmonary disease.

Outcome of inappropriate empirical antibiotic therapy in patients with Staphylococcus aureus bacteraemia: analytical strategy using propensity scores

Patients with Staphylococcus aureus bacteraemia (SAB) who received either inappropriate or appropriate empirical therapy were compared by using two risk stratification models: (1) a cohort study using a propensity score to adjust for confounding by empirical treatment assignment; and (2) a propensity-matched case-control study. Inappropriate empirical therapy was modelled on the basis of patient characteristics, and included in the multivariate model to adjust for confounding. For case-matching analysis, patients with inappropriate empirical therapy (cases) were matched to those with appropriate empirical therapy (controls) on the basis of the propensity score (within 0.03 on a scale of 0-1). In total, 238 patients with SAB were enrolled in the cohort study. Characteristics associated with inappropriate empirical therapy were methicillin resistance, underlying haematological malignancy, no history of colonisation with methicillin-resistant S. aureus, and a long hospital stay before SAB. These variables were included in the propensity score, which had an area under the receiver operating characteristics curve of 85%. In the cohort study, SAB-related mortality was 39% (45/117) for inappropriate empirical therapy vs. 28% (34/121) for appropriate empirical therapy (odds ratio (OR) 1.60; 95% CI 0.93-2.76). After adjustment for independent predictors for mortality and the propensity score, inappropriate empirical therapy was not associated with mortality (adjusted OR 1.39; 95% CI 0.62-3.15). In the matched case-control study (50 pairs), SAB-related mortality was 32% (16/50) for inappropriate empirical therapy and 28% (14/50) for appropriate empirical therapy (McNemar's test; p 0.85; OR 1.15; 95% CI 0.51-2.64). In conclusion, inappropriate empirical therapy resulted in only a slight tendency towards increased mortality in patients with SAB.

Inappropriate Initial Empirical Antibiotic Therapy in Abdominal-Surgery Patients

Various investigators have reported unfavorable outcomes for patients with severe infections who have received inappropriate initial empirical

Purulent Pericarditis.

Purulent pericarditis represents a subset of pericardial disease usually due to a nonviral infectious agent. The presentation is often acute, with rapid progression to tamponade unless a drainage procedure is performed. Although several infectious agents account for the majority of infections, the differential diagnosis is broad. Often, patients with more exotic infectious causes have risk factors for these agents that can be identified by careful history-taking. Distinguishing a bacteremic source from infection acquired by contiguous spread is particularly important. Although most infections spread contiguously are a complication of recent surgery or nearby pneumonia and are, therefore, apparent to the physician, others may be less obvious. For example, head and neck space infections may track to the retropharyngeal space and, from there, posteriorly to the so-called "danger" space, which connects inferiorly to the mediastinum and the pericardium. Failing to identify this source of tracking infection may lead to inadequate drainage as well as inappropriate empiric antibiotic therapy. In acute cases, needle drainage with appropriate staining and culturing of the fluid is adequate for diagnosis and initial management of the complications of fluid collection in the closed space of the pericardial sac. Pericardial biopsy may be the sole method of identifying an etiologic agent, particularly in chronic cases in which granulomatous disease is more commonly seen. In select cases, pericardial window or pericardiectomy procedures are needed to limit complications of reaccumulation of fluid.

Bacteremic pneumonia in neutropenic patients with cancer: causes, empirical antibiotic therapy, and outcome.

Bacteremic pneumonia is a major cause of death among neutropenic patients with cancer. We analyzed the causes, empirical antibiotic therapy, and outcome of 40 consecutive cases of bacteremic pneumonia identified among 408 episodes of bacteremia in adult neutropenic patients with cancer, prospectively documented from 1986 to 1995. The most frequent causative organisms were Pseudomonas aeruginosa (17 cases), Streptococcus pneumoniae (12 cases), Escherichia coli (5 cases), and Streptococcus mitis (3 cases). Overall, P. aeruginosa and S. pneumoniae caused 72.5% of all episodes of bacteremic pneumonia, compared with 11.4% of bacteremic episodes from other sources (P< .001). Thirty patients received ceftazidime and 10 patients received imipenem as the beta-lactam component of the initial empirical treatment. All strains of P. aeruginosa were susceptible to both agents. Forty-seven percent of streptococcal strains were penicillin resistant and showed a decreased susceptibility to ceftazidime (minimum inhibitory concentration ranged from 1 to 64 microg/mL). Five patients (12.5%) were considered to have received inappropriate empirical antibiotic therapy. Attributable mortality in patients with bacteremic pneumonia was higher than in patients with bacteremia from other sources; 22 (55%) of the 40 patients with bacteremic pneumonia died, whereas 39 (10.6%) of the 368 patients with bacteremia from other sources died (P<.001). Our data suggest that bacteremic pneumonia in neutropenic cancer patients is associated with a poor outcome and that empirical antibiotic therapy for neutropenic patients with pneumonia should include agents active against both P. aeruginosa and cephalosporin-resistant streptococci.

Treatment of penicillin-resistant pneumococcal bacteremia in neutropenic patients with cancer.

We identified 17 cases of pneumococcal bacteremia among 340 neutropenic cancer patients with bacteremia. Pneumonia was more frequent in patients with pneumococcal bacteremia than in those with bacteremia due to other organisms: 12 (71%) of 17 patients with pneumococcal bacteremia had pneumonia, whereas only 23 (7%) of 323 patients with nonpneumococcal bacteremia had pneumonia (P < .001). Eight (47%) of the 17 episodes of pneumococcal bacteremia were caused by penicillin-resistant strains (MICs ranged from 0.12 microg/mL to 4 microg/mL); these penicillin-resistant pneumococci showed varying degrees of diminished susceptibility to all beta-lactams studied, especially ceftazidime (MICs of this drug ranged from 1 microg/mL to 64 microg/mL). Imipenem was the beta-lactam agent most active against these organisms (MICs ranged from 0.03 microg/mL to 0.25 microg/mL). Patients with penicillin-resistant pneumococcal bacteremia received inappropriate empirical antibiotic therapy more often than did patients with bacteremia due to susceptible strains (i.e., 4 (50%) of 8 patients vs. 0 of 9, respectively; P < .05). Eight (47%) of the 17 patients with pneumococcal bacteremia died. In areas where penicillin-resistant pneumococci are highly endemic, these findings should be considered in selecting empirical antibiotic therapy for neutropenic patients with cancer who are suspected of having pneumonia.

Factors associated with increased risk in inappropriate empiric antibiotic treatment of childhood bacteraemia.

To identify bacteraemic children who are at increased risk of inappropriate empiric antibiotic therapy, we performed univariate and multivariate analyses of prospectively-studied bacteraemic episodes. Appropriateness of therapy was defined according to the in vitro susceptibility of the isolate. Inappropriate empiric therapy was found in 38% of 516 bacteraemic episodes and was associated with higher mortality. The rate of inappropriate treatment was lower in neonates and infants (28% and 33%, respectively) but higher in children 1- to 5-years old (51%, P = 0.0029). The rate was dependent on the source of bacteraemia (range, 18%-70%, P = 0.0092), underlying conditions (range, 26%-53%, P = 0.0001), the specific paediatric section in which the child was hospitalized (range, 24%-70%, P = 0.0002), and the causative micro-organism (range, 15%-75%, P < 0.0001). Four clinical variables that independently and significantly affected the rate of inappropriate antibiotic treatment were identified by multivariate stepwise logistic regression analysis (odds ratios in parentheses): hospital-acquired bacteraemia (2.3), age of 1- to 5-years (2.1), cytotoxic therapy (1.8) and presence of central i.v. line (1.6). We defined bacteraemic children who are at risk of inappropriate empiric antibiotic therapy. Special efforts are needed to improve their treatment and consequently their outcome.