ROTATING ANTIBIOTIC CLASSES LOWERS THE ODDS OF INADEQUATE THERAPY

Scheduled changes in the predominant antibiotic class used empirically to treat suspected gram-negative bacterial infections may reduce the incidence of inadequate therapy, reported the authors of a prospective study. This approach may be of greatest benefit to the most severely ill patients.

Kollef et al evaluated 3,668 critically ill patients who were treated in one urban teaching hospital during three consecutive time periods of six, six, and five months. During each time period, a specific class of antibiotics was used empirically to treat proven or suspected gram-negative bacterial infections:

• Period 1: Ceftazidime, a third-generation cephalosporin (n =1,323).
• Period 2: Ciprofloxacin, a fluoroquinolone (n = 1,243).
• Period 3: Cefepime, a fourth-generation cephalosporin (n = 1,102).

Throughout the study, each patient's physician had the authority to prescribe vancomycin and/or aminoglycoside antibiotics as needed. The primary outcome measure was inadequate treatment of nosocomial infections.

During the study, infections were identified in 1,371 patients. The infections were nosocomial in 517 patients; 125 patients had both community-acquired and nosocomial infections.

The incidence of inadequate antimicrobial therapy decreased from 6.1% to 4.5% during the study's course, largely because of a significant decrease in the incidence of inadequate treatment of gram-negative bacterial infections (from 4.4% to 1.6%). In-hospital mortality was similar during each of the study periods (15.6%, 16.4%, and 16.2%, respectively) despite a significant increase in illness severity. However, for the most severely ill patients (those with an APACHE II score of 15 or higher), in-hospital mortality was significantly lower during period 3 than during periods 1 and 2.

Multivariate analysis showed that inadequate antimicrobial treatment of nosocomial infection was the most important risk factor for in-hospital mortality.

Kollef MH, Ward S, Sherman G, et al. Inadequate treatment of nosocomial infections is associated with certain empiric antibiotic choices. Crit Care Med. 2000;28:3456-3464.

MEDICAL WASTE MAY BE A SOURCE OF M TUBERCULOSIS

Contaminated medical waste is a potential source of Mycobacterium tuberculosis infection, according to the results of a recently published environmental study.

Johnson et al studied three employees of a Washington State waste treatment facility who presented with pulmonary tuberculosis. After intensive investigation, the authors concluded that the source of the infections was occupational exposure to infectious medical waste. Among their findings:

There was no evidence that the infections occurred as a result of exposure to an infected person in the community. DNA fingerprinting also ruled out worker-to-worker transmission.

• Forty-five percent of fellow employees of the three workers had positive tuberculin skin test results.

• Forty-nine percent of Washington State laboratories shipped viable M tuberculosis cultures to medical waste disposal facilities.

• An environmental investigation of the waste disposal facility indicated that workers could have been exposed to contaminated aerosols released by shredded waste in a manner that made them susceptible to infection.

• A DNA fingerprint pattern for an isolate from one of the workers was identical to the pattern for an isolate from a patient whose only exposure had been to the medical waste.

The authors recommended that laboratories review their procedures for disposal of viable M tuberculosis material and that waste treatment facilities not accept contaminated laboratory waste. In addition, people who work with medical waste should undergo extensive and continuous safety training.

Johnson KR, Braden CR, Cairns KL, et al. Transmission of Mycobacterium tuberculosis from medical waste. JAMA. 2000;284:1683-1688.

CLINICAL INDEX PREDICTS ASTHMA RISK IN YOUNG CHILDREN

Simple, easily obtainable clinical criteria can be used in infants and young children to predict their subsequent risk of asthma, data from the Tucson Children's Respiratory Study suggest.

Castro-Rodríguez et al used these data to develop and compare two clinical indexes to assess asthma risk. The criteria in the "stringent" index included frequent wheezing during the first three years of life and either one major risk factor (physician-diagnosed eczema or a parental history of asthma) or two of three minor risk factors (physician-diagnosed allergic rhinitis, wheezing without colds, and eosinophilia of 4% or greater).

The criteria in the "loose" index included any wheezing during the first three years of life plus the aforementioned major and minor risk factors. The information needed to apply the loose and stringent indexes was available for 986 and 1,002 children, respectively.

Children who met the criteria for the loose index were 2.6 to 5.5 times more likely to develop asthma at some time during their school years than were those who did not meet these criteria. Children who met the criteria for the stringent index were 4.3 to 9.8 times more likely to subsequently have asthma than were the other children. More than 95% of the children who did not meet the criteria for the stringent index never experienced any symptoms of asthma.

Castro-Rodr’guez et al calculated that the loose index had a sensitivity of 41.6%, specificity of 84.7%, positive predictive value of 59.1%, and negative predictive value of 73.2% for subsequent asthma. For the stringent index, the corresponding figures were 15.7%, 97.4%, 76.6%, and 68.3%.

The Tucson Children's Respiratory Study is a longitudinal evaluation of respiratory illnesses in children.

Castro-Rodr’guez JA, Holberg CJ, Wright AL, Martinez FD. A clinical index to define risk of asthma in young children with recurrent wheezing. Am J Respir Crit Care Med. 2000;162:1403-1406.

RESPIRATORY COMPLICATIONS AFTER PEDIATRIC BONE MARROW TRANSPLANTATION

Pediatric bone marrow transplantation (BMT) carries a risk of severe pulmonary complications. However, the likelihood of death from such complications has dropped markedly in the past decade.

Griese et al reviewed outcomes among 138 patients (ages 1.1 to 22.4 years) who received an aggregate total of 152 BMTs during the period from 1975 to 1999. Thirty of the transplants were autologous; for the other procedures, allogeneic bone marrow was obtained from 99 HLA-identical siblings and from 23 other donors.

Severe pulmonary complications developed in 17 patients, 12 of whom died of respiratory failure. Six early deaths were due to fungal, bacterial, or viral pneumonia; a seventh resulted from acute pulmonary edema. These deaths occurred during the first few months posttransplant, when the patients were neutropenic. All but one of these deaths occurred before 1990.

Ten patients developed late severe respiratory complications (respiratory symptoms that persisted for more than four months and were unresponsive to treatment). These patients all had graft-versus-host disease. The five deaths in this group were due to bronchiolitis obliterans, pulmonary fibrosis, and idiopathic pneumonia syndrome.

An analysis of 69 patients who underwent BMT in each of two time periods--before and after 1990--showed that the probability of death from severe respiratory complications fell from 23% during the earlier period to 4% during the latter. The authors attributed the improved survival to better HLA matching, fewer transplantations performed in patients with relapsed or primary progressive disease, and improved supportive care. They also suggested that as transplant centers have learned to better prevent the infectious sequelae of BMT, graft-versus-host disease and mismatched transplants have become the strongest risk factors for severe pulmonary complications.

Griese M, Rampf U, Hofmann D, et al. Pulmonary complications after bone marrow transplantation in children: twenty-four years of experience in a single pediatric center. Pediatr Pulmonol. 2000;30:393-401.

DIAGNOSING ASPIRIN-INTOLERANT ASTHMA

A new noninvasive technique--acoustic rhinometry--can effectively determine the nasal response to a lysine acetylsalicylic acid (L-ASA) challenge, a prospective, double-blind study indicates. It can be used as a diagnostic test for aspirin sensitivity even in asthmatic patients with severe bronchial obstruction.

Casadevall et al evaluated the utility of acoustic rhinometry after intranasal L-ASA challenge in 31 subjects. Fifteen had aspirin-intolerant asthma and rhinitis, and eight had aspirin-tolerant asthma and rhinitis; eight healthy subjects served as controls. All subjects were challenged with saline and 25 mg L-ASA in each nostril on two separate occasions at least one week apart. Acoustic rhinometry was used to determine the volume of the nasal cavity in the two hours after the nasal challenge.

The response to placebo was similar in all three groups. However, the response to L-ASA varied markedly. In comparison with the aspirin-tolerant patients and controls, those with aspirin-intolerant asthma and rhinitis experienced a significant decrease in nasal cavity volume. The change in volume first became apparent 50 minutes postchallenge and lasted through the end of the two-hour study.

The L-ASA challenge also produced a marked increase in clinical symptoms--primarily nasal congestion and rhinorrhea--in the aspirin-intolerant patients. Neither the aspirin-tolerant patients nor the controls experienced a similar increase in symptoms.

The authors suggested that a decrease in nasal cavity volume of 25% or more can be used to diagnose aspirin-intolerant asthma. In their study, this cutoff point yielded a specificity of 94% and a sensitivity of 73% for the diagnosis.

Casadevall J, Ventura P-J, Mullol J, Picado C. Intranasal challenge with aspirin in the diagnosis of aspirin-intolerant asthma: evaluation of nasal response by acoustic rhinometry. Thorax. 2000;55:921-924.