Inadequate Antimicrobial Therapy Research Articles

Empirical antimicrobial therapy of septic shock patients: adequacy and impact on the outcome.

To assess the adequacy of empirical antimicrobial therapy prescribed in septic shock patients and to evaluate the relationship between inadequate antimicrobial therapy and 30-day mortality. Prospective observational study. Medical-surgical (16-bed) intensive care unit in an urban teaching hospital. A total of 107 patients requiring intensive care admission were prospectively evaluated during the 3-yr period of the study. Prospective patient surveillance and data collection and assessment of antimicrobial therapy according to microbiological documentation. A source of infection associated with a microbiological documentation was identified in 78 of the 107 patients (72%). Empirical antimicrobial therapy consisted of a pivotal antibiotic (beta-lactam) associated with an aminoglycoside (59 patients) or a fluoroquinolone (21 patients). Vancomycin was added in 14 patients. Sixty-nine of the 78 patients (89%) received an adequate antimicrobial therapy. The mortality rate of patients receiving an adequate antimicrobial therapy was 56%, and seven of the nine patients (78%) receiving an inadequate antimicrobial therapy died (p =.2). Among the 81 patients who were alive on day 3, antimicrobial therapy was modified in agreement to clinical status and microbiological documentation in 80% of cases, with de-escalation in 64% of cases. De-escalation consisted of withdrawing the nonpivotal antibiotic in 42% of patients or switching to a narrow-spectrum beta-lactam antibiotic (22% of cases). The prescription of empirical antimicrobial therapy by a senior physician in agreement with practice guidelines made it possible to achieve a crude rate of 89% of adequate antimicrobial therapy in study patients. Inadequate antimicrobial therapy was associated with a 39% excess of mortality. A de-escalation of the empirical therapy was possible in 64% of patients.

Appropriate use of antimicrobial agents: challenges and strategies for improvement.

The use of inadequate empirical antimicrobial therapy is common in intensive care unit patients and contributes to a number of poor outcomes. Selecting appropriate antimicrobial therapy is complicated by many factors, including the large number of agents available, the presence of resistant organisms, and the general desire among practitioners to use the most focused therapy available. An important aspect of appropriate antimicrobial use is prompt initiation of adequate empirical therapy, which has been shown to improve mortality rates in hospitalized patients with pneumonia and other serious infections. Other key strategies include streamlining antimicrobial therapy when a pathogen is identified and switching from intravenous to oral therapy when clinically indicated. In addition, antibiotic rotation (or cycling) has been evaluated in several trials as a means to minimize resistance. Promoting appropriate antimicrobial therapy ultimately will require a multidisciplinary, system-oriented, institution-specific approach because each intensive care unit has its own unique flora and antimicrobial resistance patterns.

Factores pronósticos de la bacteriemia: estudio prospectivo

To identify the epidemiology and risk factors with influence in the outcome and mortality of a series of bacteriemic patients. A prospective study of bloodstream infections with clinical significance detected in a secondary hospital of 650 beds over period from May 1998 to May 1999. The true bacteriemia was defined in basis to the criteria both the physician and microbiologist. A total of 16 variables were defined and categorized such as clinical-epidemiologic, intrinsic risk factor, extrinsic risk factor, outcome and survival. We used SPSS statistical package: For cuantitative variables we carried out with the mean with confidence interval of 95%, for cualitative variables: number and %. Univariate analysis of the results was carried out with the X2 test and t Student, the survival was expressed with Kaplan Meyer graphics and the logistic regression model. A total of 320 positive blood cultures were studied but only 272 blood cultures were considered true bacteriemia in 259 patients. The calculated incidence of significant episodes of bacteriemia per 1000 admissions/year was 13. The overall mortality was 22% whereas death attributable to bacteriemia was 16%. The mean age was 66.9 years (IC 95% 65-69), 59% episodes occurred in men. The 78% episodes occurred in patients hospitalized in medical services. 52% episodes were of nosocomial infection and 48% of community acquired infection. According to the severity of the underlying disease, 15% had fatal diseases and 35% episodes occurred in patients without underlying disease. According to the univariant analysis, the variables which where significantly associated with greater risk death were: etiology (fungus), septic shock, the inadequate antibiotic therapy, presence of extrinsic factors (central intravenous catheter, performance of invasive procedures, previous antimicrobial therapy) and the hospital stay of less than 10 days. According to the multivariable analysis showed that the factors remaining independent predictors of mortality were: septic shock (p < 0.0001, OR: 8), inadequate antimicrobial therapy (p < 0.005, OR: 6.7), existence of two or more extrinsic risk factors (p < 0.04). The presence of septic shock was the most important variable which influenced in the mortality in our serie, together with inappropriate antimicrobian therapy and the association of various extrinsic risk factors. These variables could be modified partly, for this reason the aggressive hemodynamic control and the early and appropriate antibiotic therapy would be the support of the successful bacteriemia management.

Is there a role for antibiotic cycling in the intensive care unit?

Antibiotic resistance of bacterial pathogens has emerged as one of the most important issues facing critical care practitioners. Resistance of many commonly encountered bacterial species is increasing and has been associated with greater administration of inadequate antimicrobial therapy to patients within intensive care units. This has resulted in greater patient morbidity, higher mortality rates, and increased healthcare costs. Methods to reduce antimicrobial resistance have focused on increasing adherence to infection control practices and improving antibiotic utilization. Antibiotic cycling is a strategy to reduce antimicrobial resistance by withdrawing an antibiotic or antibiotic class from use and subsequently reintroducing it at a later point in time. The main goal of cycling is to allow resistance rates for specific antibiotics to decrease, or at least remain stable, when their use is periodically eliminated from the intensive care unit.

Etiology of severe pneumonia in the very elderly.

The etiology of severe pneumonia requiring mechanical ventilation in the very elderly has been imprecise because of lack of comprehensive studies and low yield of diagnostic approach. Overall, 104 patients 75 yr of age and older with severe pneumonia were studied prospectively at two university-affiliated hospitals. Microbial investigation included blood culture, serology, pleural fluid, and bronchoalveolar secretions. Streptococcus pneumoniae (14%), gram-negative enteric bacilli (14%), Legionella sp. (9%), Hemophilus influenzae (7%), and Staphylococcus aureus (7%) were the predominant pathogens in community-acquired pneumonia (CAP). Staphylococcus aureus (29%), gram-negative enteric bacilli (15%), Streptococcus pneumoniae (9%), and Pseudomonas aeruginosa (4%) accounted for most isolates of nursing home-acquired pneumonia (NHAP). The case fatality rate was 55% (53% for CAP and 57% for NHAP; p > 0.5). Activity of Daily Living (ADL) Index, pulmonary, endocrine and central nervous system (CNS) comorbidities were associated with distinct microbial etiology. By multivariate analysis, hospital mortality was associated independently with 24-h urine output (odds ratio [OR], 5.6; 95% confidence interval [CI], 2.5 to 7.9; p < 0.001), septic shock (OR, 4.3; 95% CI, 1.9 to 8.9; p = 0.0059), radiographic multilobar involvement (OR, 3.7; 95% CI, 1.8 to 15.6; p = 0.02), and inadequate antimicrobial therapy (OR, 2.6; 95% CI, 1.4 to 23.9; p = 0.034). Further studies should focus on identifying effective antimicrobial regimens in randomized trials.

Genetic markers in sepsis

Sepsis is a systemic response to severe infection. Clinical sepsis is defined as an infection-induced syndrome including at least two of the features of systemic inflammatory response syndrome: fever or hypothermia (oral temperature .38°C or ,36°C); leukocytosis (.12,000 WBC/mm) or leukopenia (,4,000 WBC/ mm); tachycardia (heart rate .90 beats/minute); and tachypnea (.24 breaths/minute). The causes of the sepsis syndrome are both complex and obscure. Despite advances in the diagnosis and treatment of infectious disease, the appearance of a systemic inflammatory response remains a common sequela of bacterial, viral, or fungal infection. The progression from sepsis to severe sepsis (sepsis with dysfunction of one organ), to multiple organ dysfunction syndrome (MODS), and then to septic death marks steps that typically require escalation of treatment. Although patients with severe sepsis have been treated experimentally with antiinflammatory and immunomodulatory agents, no single agent has reduced the overall mortality. Sepsis remains a major unsolved health problem. The incidence of sepsis has increased during the last 20 years, with more than 500,000 patients developing sepsis each year in the US. The mortality rate is between 35% and 45%. Half of these patients die from a condition that independently predisposes to sepsis (such as severe injury), but at least 100,000 deaths are caused by sepsis alone. Sepsis is the 13th leading cause of death in the US, with a cost of $5 to $10 billion a year. The morbidity and mortality of sepsis were historically ascribed to delayed diagnosis and inadequate antimicrobial therapy. Although diagnostic delays and inadequate therapy undoubtedly occur, many appropriately treated patients fail to recover. More recently, attention has turned to the host response as a determinant of outcomes. Such patient-specific responses, in turn, reflect both heritable (or genetic) characteristics and acquired illnesses. The purpose of this article is to discuss what is known concerning the heritable characteristics of the genetic predisposition to sepsis. Particular heritable characteristics may be causal or, alternatively, represent associations with human disease. The distinction is important. The surgeon occasionally confronts inborn “errors” in single genes that alter protein structure or expression in a way that profoundly affects physiology. For example, the single amino acid substitution that changes ordinary adult Hemoglobin A to Hemoglobin S accounts for the pathology of sickle cell anemia. The surgeon also encounters acquired abnormalities in specific genes and their proteins, particularly abnormalities in regulatory tumor suppressor genes and their proteins. For example, colon mucosa sustaining spontaneous mutagenesis acquires a series of variants in specific genes that collectively facilitate the transition from normal to malignant epithelium. In both of these examples, causality has been demonstrated by fulfillment of modern expressions of Koch’s postulates using genetic manipulation: correction of the molecular abnormality (genotype) corrects the physiology (phenotype). Sepsis is different. Human genetics has not, and likely will not, identify a single or even several genes whose structure or expression fully determines predisposition to or outcomes from sepsis; sepsis alters the expression of hundreds of genes in dozens of tissues. Experimental attempts to modify expression or effect of particular genes using biologic therapeutics, such as the soluble tumor necrosis factor receptor and the interleukin 1 receptor antagonist in order to modify outcomes from clinical sepsis, have failed. This article does not address causality of sepsis. Rather, it examines associations between particular genetic markers (DNA sequences) and sepsis.

Mortality increased with inadequate antimicrobial therapy

Mortality increased with inadequate antimicrobial therapy

Blood Cultures Have Limited Value in Predicting Severity of Illness and as a Diagnostic Tool in Ventilator-Associated Pneumonia

To define the usefulness of blood cultures for confirming the pathogenic microorganism and severity of illness in patients with ventilator-associated pneumonia (VAP). Prospective observational study using BAL and blood cultures collected within 24 h of establishing a clinical diagnosis of VAP. A 15-bed medical and surgical ICU. One hundred and sixty-two patients receiving mechanical ventilation hospitalized for > 72 h who had new or progressive lung infiltrate plus at least two of three clinical criteria for VAP. BAL and blood culture performed within 24 h of establishing a clinical diagnosis of VAP. Ninety patients were BAL positive (BAL+), satisfying a microbiological definition of VAP (>/= 10(4) cfu/mL), 72 patients were BAL negative (BAL-). Bacteremia was diagnosed when at least two sets of blood cultures yielded a microorganism or when only one set was positive, but the same bacteria was present at a concentration >/= 10(4) cfu/mL in the BAL fluid. Bacteremia was significantly more frequent in the BAL+ than in the BAL- group (22/90 patients vs 5/72 patients; p = 0.006). In 6 of 22 BAL+ patients with bacteremia, an extrapulmonary site of infection was the source of bacteremia. Sensitivity of blood culture for disclosing the pathogenic microorganism in BAL+ patients was 26%, and the positive predictive value to detect the pathogen was 73%. Factors associated with mortality were age > 50 years, simplified acute physiology score > 14, prior inadequate antibiotic therapy, PaO(2)/fraction of inspired oxygen < 205, and use of H(2) blockers. By multivariate analysis, only the use of prior inadequate antimicrobial therapy (odds ratio [OR], 6.47) and age > 50 years (OR, 5.12) were independently associated with higher mortality. The rate of complications was not different in patients with bacteremia. Blood cultures have a low sensitivity for detecting the same pathogenic microorganism as BAL culture in patients with VAP. The presence of bacteremia does not predict complications, it is not related to the length of stay, and it does not identify patients with more severe illness. Inadequacy of prior antimicrobial therapy and age > 50 years were the only factors associated with mortality in a multivariate analysis. Blood cultures in patients with VAP are clearly useful if there is suspicion of another probable infectious condition, but the isolation of a microorganism in the blood does not confirm that microorganism as the pathogen causing VAP.

The approach to nonresol ving pneumonia

Pneumonias that fail to resolve at the expected rate may reflect derangements in host defenses, inadequate or inappropriate antimicrobial therapy, highly virulent pathogens, or myriad noninfectious causes. In this article, noninfectious causes of pulmonary infiltrates mimicking community-acquired pneumonia are discussed. The salient clinical, radiographic, and histopathologic features of diverse immune-mediated syndromes are reviewed, and an approach to diagnosis and therapy of nonresolving pneumonias is presented.

Intestinal Perforation in Typhoid Fever: A Historical and State-of-the-Art Review

The appropriate therapy for intestinal perforation in typhoid fever has been controversial since the late 1880s. Around the turn of the century, surgery became the established mode of therapy, with a mortality of 69% based on 166 patients in the English-language medical literature, and continued to be the preferred treatment until the advent of chloramphenicol in 1948. At this time the surgical mortality was approximately 50%. Following the recovery of a few patients with perforation treated only with antimicrobial agents (six initially, then eventually 22), nonsurgical therapy became the accepted mode of treatment. This change was never justified and this review demonstrates this. Appropriate therapy is virtually always surgical, usually consisting of simple closure and irrigation. Chloramphenicol alone is inadequate antimicrobial therapy in a patient with perforation and must be supplemented by other antimicrobials directed against enteric aerobic gram-negative bacilli and enteric anaerobes.

Laboratory perspective of gram staining and its significance in investigations of infectious diseases

Clinical microbiology laboratory plays several important roles in the management of bacterial infections. Isolation, identification of pathogenic microorganisms in cultures and subsequent antimicrobial susceptibility testing always assists in selecting appropriate antimicrobial agent and prevention of unnecessary complications. The most important and primary test to perform directly on some special samples such as cerebrospinal fluid and positive cultures is Gram staining which serves as the most rapid and simplest test to characterize microorganisms. It is therefore highly likely that the information provided by the Gram staining will help to assess the adequacy of preliminary diagnosis and antimicrobial therapy selected after collecting culture specimens and before final identification of the microorganism. In recent reports, the impact of Gram staining results on patient mortality has been documented. On the other hand, there remains the possibility that Gram staining results do not match with the final identification of microorganisms. This would carry a risk leading to inadequate antimicrobial therapy and potentially affecting patients' clinical course and mortality. The aim of this mini review is to analyze and discuss the clinical significance and limitations of reporting Gram staining results for sample meant for bacteriological investigations.

Comparative Morbidity and Mortality of Antimicrobially Treated and Untreated Idiopathic Effusion in the Negro

1Forty-seven American Negroes with idiopathic pleural effusion were treated with bed rest of variable duration together with therapeutic aspiration. Sixty-four per cent of them developed proved tuberculosis during a minimum follow-up of five years. Twenty-one per cent of them died. 2during the same period of time and under the same hospital conditions, 45 American Negroes were given chemotherapy, most of which was inadequate by present day standards, and were then followed for a similar period of time. Of this group 17.7 per cent developed postpleuritic tuberculosis, and 4.4 per cent died. Even inadequate antimicrobial therapy was able to alter significantly postpleuritic morbidity and mortality from tuberculosis. The mortality among the untreated group exceeded the morbidity among the treated. 3Pleural and thoracic complications of serofibrinous effusion were significantly fewer and less severe following antimicrobial therapy. 4Our data suggest that inadequate antimicrobial therapy may prolong the interval between effusion and relapse in the American Negro. 5Our studies confirm the findings of others: bilateral pleural effusion, polyserositis, and extrathoracic tuberculosis are more common in the adult American Negro than in the Caucasian. 6It is our belief that idiopathic pleural effusion in the American Negro is a particularly serious event, and when it is associated with a positive tuberculin reaction, should be treated as miliary tuberculosis.