Antibiotic Susceptibility Among Aerobic Gram-negative Bacilli in Intensive Care Units in 5 European Countries

Context  Surveillance of antibiotic resistance is especially important in intensive care units (ICUs) because the infection rates are much higher there than in other hospital wards and most epidemics with multiresistant bacteria originate in ICUs. Objective  To evaluate the incidence of decreased antibiotic susceptibility among aerobic gram-negative bacilli isolated from patients in ICUs. Design  Consecutive specimens collected on clinical indications from ICU patients were cultured and tested. Minimum inhibitory concentrations for amikacin, ceftazidime, ceftriaxone, ciprofloxacin, gentamicin, imipenem, piperacillin, and piperacillin-tazobactam were determined using E test. Setting  Eighteen hospitals in Belgium, 40 in France, 20 in Portugal, 30 in Spain, and 10 in Sweden. Subjects  A total of 9166 gram-negative strains were initially isolated from 7308 patients between June 1994 and June 1995. Main Outcome Measures  The incidence of decreased susceptibility, defined as the sum of resistant and intermediate categories with use of the minimum inhibitory concentration break points recommended by the National Committee for Clinical Laboratory Standards. Results  The most frequently isolated organisms were Enterobacteriaceae (59\%) followed by Pseudomonas aeruginosa (24\%). The main sources were respiratory tract (42\%), urine (26\%), blood (14\%), abdomen (11\%), and skin and soft tissue (7\%). Decreased antibiotic susceptibility across all species and drugs was highest in Portuguese ICUs followed by French, Spanish, Belgian, and Swedish ICUs. The highest incidence of resistance was seen in all countries among P aeruginosa (up to 37\% resistant to ciprofloxacin in Portuguese ICUs and 46\% resistant to gentamicin in French ICUs), Enterobacter species, Acinetobacter species, and Stenotrophomonas maltophilia, and in Portugal and France among Klebsiella species. Conclusion  The high incidence of reduced antibiotic susceptibility among gram-negative bacteria in these ICUs suggests that more effective strategies are needed to control the selection and spread of resistant organisms.      

Prevalence and trends in overweight among US children and adolescents, 1999-2000

Context  The prevalence of overweight among children in the United States increased between 1976-1980 and 1988-1994, but estimates for the current decade are unknown. Objective  To determine the prevalence of overweight in US children using the most recent national data with measured weights and heights and to examine trends in overweight prevalence. Design, Setting, and Participants  Survey of 4722 children from birth through 19 years of age with weight and height measurements obtained in 1999-2000 as part of the National Health and Nutrition Examination Survey (NHANES), a cross-sectional, stratified, multistage probability sample of the US population. Main Outcome Measure  Prevalence of overweight among US children by sex, age group, and race/ethnicity. Overweight among those aged 2 through 19 years was defined as at or above the 95th percentile of the sex-specific body mass index (BMI) for age growth charts. Results  The prevalence of overweight was 15.5% among 12- through 19-year-olds, 15.3% among 6- through 11-year-olds, and 10.4% among 2- through 5-year-olds, compared with 10.5%, 11.3%, and 7.2%, respectively, in 1988-1994 (NHANES III). The prevalence of overweight among non-Hispanic black and Mexican-American adolescents increased more than 10 percentage points between 1988-1994 and 1999-2000. Conclusion  The prevalence of overweight among children in the United States is continuing to increase, especially among Mexican-American and non-Hispanic black adolescents.      

The Medical Costs of Gunshot Injuries in the United States

Context  The cost of treating gunshot injuries imposes a financial burden on society. Estimates of such costs are relevant to evaluation of gun violence reduction programs and may help guide reimbursement policies. Objectives  To develop reliable US estimates of the medical costs of treating gunshot injuries and to present national estimates for the sources of payment for treating these injuries. Design and Setting  Cost analysis using E-coded discharge data from hospitals in Maryland for 1994-1995 and New York for 1994 and from emergency departments in South Carolina for 1997. Other sources of data included the National Electronic Injury Surveillance System for 1994 incidence of nonfatal gun injuries, the National Spinal Cord Injury Statistical Center database for 1988-1992 estimates of lifetime medical costs of gun injuries, and the 1994 Vital Statistics census for incidence of fatal gun injuries. Main Outcome Measures  Estimated national acute-care and follow-up treatment costs and payment sources for gunshot injuries. Results  At a mean medical cost per injury of about $17,000, the 134,445 (95% confidence interval [CI], 109,465-159,425) gunshot injuries in the United States in 1994 produced $2.3 billion (95% CI, $2.1 billion–$2.5 billion) in lifetime medical costs (in 1994 dollars, using a 3% real discount rate), of which $1.1 billion (49%) was paid by US taxpayers. Gunshot injuries due to assaults accounted for 74% of total costs. Conclusions  Gunshot injury costs represent a substantial burden to the medical care system. Nearly half this cost is borne by US taxpayers.      

Secular trends in nosocomial infections and mortality associated with noninvasive ventilation in patients with exacerbation of COPD and pulmonary edema

Context  Randomized controlled trials have shown that the use of noninvasive ventilation (NIV) reduces the need for endotracheal intubation and invasive mechanical ventilation and reduces complication rates and mortality in selected groups of patients. But whether these benefits translate to a clinical setting is unclear. Objective  To evaluate longitudinally the routine implementation of NIV and its effect on patients admitted to the intensive care unit (ICU) with acute exacerbation of chronic obstructive pulmonary disease (COPD) or severe cardiogenic pulmonary edema (CPE). Design  Retrospective, observational cohort study using prospectively collected data from January 1, 1994, through December 31, 2001. Setting  A 26-bed medical intensive care unit (ICU) of a French university referral hospital. Participants  A cohort of 479 consecutive patients ventilated for acute exacerbation of COPD or CPE. Main Outcome Measures  The ICU mortality and incidence rates of ICU-acquired infections. Results  A significant increase in NIV use and a concomitant decrease in mortality and ICU-acquired infection rates were observed over the study years. With adjustment for relevant covariates and propensity scores, NIV was identified as an independent factor linked with a reduced risk of death in the cohort (odds ratio [OR], 0.37; 95% confidence interval [CI], 0.18-0.78), whereas a high severity score on admission (OR, 1.05; 95% CI, 1.01-1.10) and the occurrence of a nosocomial infection (OR, 3.08; 95% CI, 1.62-5.84) were independently associated with death. Rates of ICU-acquired pneumonia decreased from 20% in 1994 to 8% in 2001 (P = .04). Conclusion  Implementing routine use of NIV in critically ill patients with acute exacerbation of COPD or severe CPE was associated with improved survival and reduction of nosocomial infections.      

Comparison of ciprofloxacin (7 days) and trimethoprim-sulfamethoxazole (14 days) for acute uncomplicated pyelonephritis pyelonephritis in women: a randomized trial

Context  The optimal antimicrobial regimen and treatment duration for acute uncomplicated pyelonephritis are unknown. Objective  To compare the efficacy and safety of a 7-day ciprofloxacin regimen and a 14-day trimethoprim-sulfamethoxazole regimen for the treatment of acute pyelonephritis in women. Design  Randomized, double-blind comparative trial conducted from October 1994 through January 1997. Setting  Twenty-five outpatient centers in the United States. Patients  Of 378 enrolled premenopausal women aged at least 18 years with clinical diagnosis of acute uncomplicated pyelonephritis, 255 were included in the analysis. Other individuals were excluded for no baseline causative organism, inadequate receipt of study drug, loss to follow-up, no appropriate cultures, and other reasons. Interventions  Patients were randomized to oral ciprofloxacin, 500 mg twice per day for 7 days (with or without an initial 400-mg intravenous dose) followed by placebo for 7 days (n = 128 included in analysis) vs trimethoprim-sulfamethoxazole, 160/800 mg twice per day for 14 days (with or without intravenous ceftriaxone, 1 g) (n = 127 included in the analysis). Main Outcome Measure  Continued bacteriologic and clinical cure, such that alternative antimicrobial drugs were not required, among evaluable patients through the 4- to 11-day posttherapy visit, compared by treatment group. Results  At 4 to 11 days posttherapy, bacteriologic cure rates were 99% (112 of 113) for the ciprofloxacin regimen and 89% (90 of 101) for the trimethoprim-sulfamethoxazole regimen (95% confidence interval [CI] for difference, 0.04-0.16; P = .004). Clinical cure rates were 96% (109 of 113) for the ciprofloxacin regimen and 83% (92 of 111) for the trimethoprim-sulfamethoxazole regimen (95% CI, 0.06-0.22; P = .002). Escherichia coli, which caused more than 90% of infections, was more frequently resistant to trimethoprim-sulfamethoxazole (18%) than to ciprofloxacin (0%; P<.001). Among trimethoprim-sulfamethoxazole–treated patients, drug resistance was associated with greater bacteriologic and clinical failure rates (P<.001 for both). Drug-related adverse events occurred in 24% of 191 ciprofloxacin-treated patients and in 33% of 187 trimethoprim-sulfamethoxazole–treated patients, respectively (95% CI, -0.001 to 0.2). Conclusions  In our study of outpatient treatment of acute uncomplicated pyelonephritis in women, a 7-day ciprofloxacin regimen was associated with greater bacteriologic and clinical cure rates than a 14-day trimethoprim-sulfamethoxazole regimen, especially in patients infected with trimethoprim-sulfamethoxazole–resistant strains.      

Effect of ethics consultations on nonbeneficial life-sustaining treatments in the intensive care setting: a randomized controlled trial

Context  Ethics consultations increasingly are being used to resolve conflicts about life-sustaining interventions, but few studies have reported their outcomes. Objective  To investigate whether ethics consultations in the intensive care setting reduce the use of life-sustaining treatments delivered to patients who ultimately did not survive to hospital discharge, as well as the reactions to the consultations of physicians, nurses, and patients/surrogates. Design  Prospective, multicenter, randomized controlled trial from November 2000 to December 2002. Setting  Adult intensive care units (ICUs) of 7 US hospitals representing a spectrum of institutional characteristics. Patients  Five hundred fifty-one patients in whom value-related treatment conflicts arose during the course of treatment. Interventions  Patients were randomly assigned either to an intervention (ethics consultation offered) (n = 278) or to usual care (n = 273). Main Outcome Measures  The primary outcomes were ICU days and life-sustaining treatments in those patients who did not survive to hospital discharge. We examined the same measures in those who did survive to discharge and also compared the overall mortality rates of the intervention and usual care groups. We also interviewed physicians and nurses and patients/surrogates about their views of the ethics consultation. Results  The intervention and usual-care groups showed no difference in mortality. However, ethics consultations were associated with reductions in hospital (-2.95 days, P = .01) and ICU (-1.44 days, P = .03) days and life-sustaining treatments (-1.7 days with ventilation, P = .03) in those patients who ultimately did not survive to discharge. The majority (87%) of physicians, nurses, and patients/surrogates agreed that ethics consultations in the ICU were helpful in addressing treatment conflicts. Conclusion  Ethics consultations were useful in resolving conflicts that may have inappropriately prolonged nonbeneficial or unwanted treatments in the ICU.      

Comparison of 8 vs 15 days of antibiotic therapy for ventilator-associated pneumonia in adults: a randomized trial

Context  The optimal duration of antimicrobial treatment for ventilator-associated pneumonia (VAP) is unknown. Shortening the length of treatment may help to contain the emergence of multiresistant bacteria in the intensive care unit (ICU). Objective  To determine whether 8 days is as effective as 15 days of antibiotic treatment of patients with microbiologically proven VAP. Design, Setting, and Participants  Prospective, randomized, double-blind (until day 8) clinical trial conducted in 51 French ICUs. A total of 401 patients diagnosed as having developed VAP by quantitative culture results of bronchoscopic specimens and who had received initial appropriate empirical antimicrobial therapy were enrolled between May 1999 and June 2002. Intervention  A total of 197 patients were randomly assigned to receive 8 days and 204 to receive 15 days of therapy with an antibiotic regimen selected by the treating physician. Main Outcome Measures  Primary outcome measures—death from any cause, microbiologically documented pulmonary infection recurrence, and antibiotic-free days—were assessed 28 days after VAP onset and analyzed on an intent-to-treat basis. Results  Compared with patients treated for 15 days, those treated for 8 days had neither excess mortality (18.8% vs 17.2%; difference, 1.6%; 90% confidence interval [CI], -3.7% to 6.9%) nor more recurrent infections (28.9% vs 26.0%; difference, 2.9%; 90% CI, -3.2% to 9.1%), but they had more mean (SD) antibiotic-free days (13.1 [7.4] vs 8.7 [5.2] days, P<.001). The number of mechanical ventilation–free days, the number of organ failure–free days, the length of ICU stay, and mortality rates on day 60 for the 2 groups did not differ. Although patients with VAP caused by nonfermenting gram-negative bacilli, including Pseudomonas aeruginosa, did not have more unfavorable outcomes when antimicrobial therapy lasted only 8 days, they did have a higher pulmonary infection-recurrence rate compared with those receiving 15 days of treatment (40.6% vs 25.4%; difference, 15.2%, 90% CI, 3.9%-26.6%). Among patients who developed recurrent infections, multiresistant pathogens emerged less frequently in those who had received 8 days of antibiotics (42.1% vs 62.0% of pulmonary recurrences, P = .04). Conclusions  Among patients who had received appropriate initial empirical therapy, with the possible exception of those developing nonfermenting gram-negative bacillus infections, comparable clinical effectiveness against VAP was obtained with the 8- and 15-day treatment regimens. The 8-day group had less antibiotic use.      

Impact of varicella vaccination on health care utilization

Context  Since varicella vaccine was first recommended for routine immunization in the United States in 1995, the incidence of disease has dropped substantially. However, national surveillance data are incomplete, and comprehensive data regarding outpatient as well as hospital utilization have not been reported. Objective  To examine the impact of the varicella vaccination program on medical visits and associated expenditures. Design, Setting, and Patients  Retrospective population-based study examining the trends in varicella health care utilization, based on data from the MarketScan databases, which include enrollees (children and adults) of more than 100 health insurance plans of approximately 40 large US employers, from 1994 to 2002. Main Outcome Measures  Trends in rates of varicella-related hospitalizations and ambulatory visits and direct medical expenditures for hospitalizations and ambulatory visits, analyzed using 1994 and 1995 as the prevaccination baseline. Results  From the prevaccination period to 2002, hospitalizations due to varicella declined by 88% (from 2.3 to 0.3 per 100 000 population) and ambulatory visits declined by 59% (from 215 to 89 per 100 000 population). Hospitalizations and ambulatory visits declined in all age groups, with the greatest declines among infants younger than 1 year. Total estimated direct medical expenditures for varicella hospitalizations and ambulatory visits declined by 74%, from an average of $84.9 million in 1994 and 1995 to $22.1 million in 2002. Conclusion  Since the introduction of the varicella vaccination program, varicella hospitalizations, ambulatory visits, and their associated expenditures have declined dramatically among all age groups in the United States.      

Emergence of domestically acquired ceftriaxone-resistant Salmonella infections associated with AmpC beta-lactamase

Context  Ceftriaxone, an expanded-spectrum cephalosporin, is an antimicrobial agent commonly used to treat severe Salmonella infections, especially in children. Ceftriaxone-resistant Salmonella infections have recently been reported in the United States, but the extent of the problem is unknown. Objectives  To summarize national surveillance data for ceftriaxone-resistant Salmonella infections in the United States and to describe mechanisms of resistance. Design and Setting  Case series and laboratory evaluation of human isolates submitted to the Centers for Disease Control and Prevention from 17 state and community health departments participating in the National Antimicrobial Resistance Monitoring System (NARMS) for enteric bacteria between 1996 and 1998. Patients  Patients with ceftriaxone-resistant Salmonella infections between 1996 and 1998 were interviewed and isolates with decreased ceftriaxone susceptibility were further characterized. Main Outcome Measures  Exposures and illness outcomes, mechanisms of resistance. Results  The prevalence of ceftriaxone-resistant Salmonella was 0.1% (1 of 1326) in 1996, 0.4% (5 of 1301) in 1997, and 0.5% (7 of 1466) in 1998. Ten (77%) of the 13 patients with ceftriaxone-resistant infections were aged 18 years or younger. The patients lived in 8 states (California, Colorado, Kansas, Massachusetts, Maryland, Minnesota, New York, and Oregon). Nine (82%) of 11 patients interviewed did not take antimicrobial agents and 10 (91%) did not travel outside the United States before illness onset. Twelve of the 15 Salmonella isolates with ceftriaxone minimum inhibitory concentrations of 16 µg/mL or higher were serotype Typhimurium but these isolates had different pulsed-field gel electrophoresis patterns. Thirteen of these 15 isolates collected between 1996 and 1998 were positive for a 631–base pair polymerase chain reaction product obtained by using primers specific for the ampC gene of Citrobacter freundii. Conclusions  Domestically acquired ceftriaxone-resistant Salmonella has emerged in the United States. Most ceftriaxone-resistant Salmonella isolates had similar AmpC plasmid-mediated resistance.      

E5 murine monoclonal antiendotoxin antibody in gram-negative sepsis: a randomized controlled trial. E5 Study Investigators

Context  Knowledge and understanding of gram-negative sepsis have grown over the past 20 years, but the ability to treat severe sepsis successfully has not. Objective  To assess the efficacy and safety of E5 in the treatment of patients with severe gram-negative sepsis. Design  A multicenter, double-blind, randomized, placebo-controlled trial conducted at 136 US medical centers from April 1993 to April 1997, designed with 90% power to detect a 25% relative risk reduction, incorporating 2 planned interim analyses. Setting  Intensive care units at university medical centers, Veterans Affairs medical centers, and community hospitals. Patients  Adults aged 18 years or older, with signs and symptoms consistent with severe sepsis and documented or probable gram-negative infection. Intervention  Patients were assigned to receive 2 doses of either E5, a murine monoclonal antibody directed against endotoxin (n = 550; 2 mg/kg per day by intravenous infusion 24 hours apart) or placebo (n = 552). Main Outcome Measures  The primary end point was mortality at day 14; secondary end points were mortality at day 28, adverse event rates, and 14-day and 28-day mortality in the subgroup without shock at presentation. Results  The trial was stopped after the second interim analysis. A total of 1090 patients received study medication and 915 had gram-negative infection confirmed by culture. There were no statistically significant differences in mortality between the E5 and placebo groups at either day 14 (29.7% vs 31.1%; P = .67) or day 28 (38.5% vs 40.3%; P = .56). Patients presenting without shock had a slightly lower mortality when treated with E5 but the difference was not significant (28.9% vs 33.0% for the E5 and placebo groups, respectively, at day 28; P = .32). There was a similar profile of adverse event rates between E5 and placebo. Conclusions  Despite adequate sample size and high enrollment of patients with confirmed gram-negative sepsis, E5 did not improve short-term survival. Current study rationale and designs should be carefully reviewed before further large-scale studies of patients with sepsis are conducted.