ICAAC/IDSA/ASTMH 2003

Conference Coverage

The following summary of selected abstracts from 3 meetings will be published in multiple parts. The 43rd Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) met in Chicago September 14-17, 2003. The Infectious Disease Society of America (IDSA) met in San Diego October 9-12, 2003. The American Society of Tropical Medicine and Hygiene met in Philadelphia December 3-7, 2003.

Stan Deresinski, MD, FACP, is Clinical Professor of Medicine, Stanford; Associate Chief of Infectious Diseases, Santa Clara Valley Medical Center and Editor of Infectious Disease Alert.

Respiratory Tract Infections

Bacterial Infections

Community-Acquired Pneumonia

In a randomized trial of oral therapies of CAP, 10 days of treatment with moxifloxacin or with amoxicillin/clavulanate plus roxithromycin each resulted in clinical cure rates of 89% (ICAAC L-1594).

Such completely oral therapies make outpatient antibiotic therapy of CAP readily feasible. Furthermore, a prospective, randomized trial found that outpatient care of patients with low-risk (PSI class II or III) CAP was as safe and effective as inpatient treatment. Relevant to this approach is the finding that the pathogen distribution was similar in patients with CAP across all Fine classes with the exception of M pneumoniae, which was more frequently identified in class I than classes II-IV. In addition, a review of hospitalized patients with CAP found that 568 had received only orally administered levofloxacin, while 500 had received an antibiotic intravenously for at least part of their course. When stratified for severity of illness, initial oral levofloxacin therapy was associated with similar clinical outcomes but with equivalent or lower lengths of stay and cost (ICAAC L-1597, IDSA 252, 302).

In an examination of 5 randomized and 1 noncomparative trials, successful clinical outcomes in patients with CAP due to S pneumoniae occurred in 276 of 297 (93%) patients who received amoxicillin/clavulanate 2000 mg/125 mg b.i.d. The success rate for 54 patients who received comparator antibiotics was 87%. Success was achieved with amoxicillin/clavulanate 2000 mg/125 mg in 24 of 25 patients infected with penicillin-resistant pneumococci and in 6 of 7 with amoxicillin MICs of 4 to 8 mg/mL (IDSA 303).

Another strategy is an early conversion from parenteral to oral antibiotic therapy. In one study, 187 patients hospitalized with severe CAP were randomized to receive antibiotics intravenously for either 7 days or for only 3 days followed, if clinically stable, by oral antibiotic to complete a total 7-day course. The switch to oral antibiotic administration after 3 days was associated with shorter length of stay and reduced costs, without significant differences in cure rate or mortality (ICAAC A-1355).

S pneumoniae

Children exposed to passive smoking had an increased rate of nasopharyngeal carriage of S pneumoniae (ICAAC G-1545).

In addition to reducing the incidence of pneumococcal disease in children younger than 5 years, administration of the pneumococcal conjugate vaccine was associated with evidence of herd immunity in a large northern California population. There was a 58% decrease in vaccine strain infections in adults aged 20-40 and a 14% decrease in those older than 60. At the same time, there was no concomitant increase in nonvaccine strain infections (IDSA 498).

In addition to producing herd immunity, widespread use of the conjugate vaccine may be favorably affecting antibiotic resistance rates in S pneumoniae. One group reported that use of this vaccine has been associated with a reduction in the prevalence of antibiotic-nonsusceptible pneumococci in the target age group. Another group found a significant increase in pneumococcal susceptibility to penicillin, erythromycin, and tetracycline following the introduction of the seven-valent pneumococcal conjugate vaccine and a concomitant decrease in infections due to the included serotypes (IDSA 482, ICAAC G-2045).

The Alexander Project reported that the rate of growth of multidrug resistance in S pneumoniae in the United States is approximately 3% per year. Three-fourths of penicillin-resistant isolates are currently also resistant to erythromycin and trimethoprim/sulfamethoxazole. In the PROTEKT study, 29% of S pneumoniae were resistant to 2 or more antibiotics, and 8.8% were resistant to 4 in the United States in 2001-2002 (IDSA 202, 203).

Increasing antimicrobial resistance is the consequence of the selective pressure exerted by antibiotic use. Consistent with this axiom, the national prevalence of penicillin-nonsusceptible S pneumoniae, macrolide-resistant S pneumoniae, and macrolide-resistant S pyogenes was directly correlated with the antibiotic selection pressure in each of 20 developed countries. On a smaller scale, household cephalosporin use appeared to be associated with an increased effect on transmission of resistant S pneumoniae among siblings when compared to penicillin class use. However, despite interventions to reduce antibiotic misuse in Tennessee, the proportion of penicillin-, cephalosporin-, and erythromycin-resistant invasive pneumococcal isolates increased between 1995 and 2001 in individuals older than 5 but remained steady in those younger than 5 (IDSA 245, ICAAC K-1406, IDSA 483).

Not all the news is bad, however. The SENTRY study of US pneumococcal isolates found a decrease in penicillin resistance from 22% in 2001 to 17% in 2002. Erythromycin resistance decreased from 30% to 26%. In the TRUST 7 study of 4377 S pneumoniae strains isolated in the United States in 2002-2003, > 99% remained susceptible to levofloxacin, gatifloxacin, and moxifloxacin (ICAAC C2-926, IDSA 201).

Two evaluations of the accuracy and usefulness of the Binax NOW™ urine antigen test in the diagnosis of invasive pneumococcal disease came to less than glowing conclusions. Evaluation of 134 children with suspected invasive disease found that the urine antigen test appeared to be useful for excluding pneumococcal infection but not, however, in distinguishing infection from colonization. In addition, a retrospective review concluded that the Binax NOW™ Streptococcus pneumoniae urine antigen assay "provided minimal additional information to standard culture in diagnosing etiology of CAP, and empiric therapy was not modified based on the results." The NOW assay was, however, effective in detecting pneumococcal antigen in empyema fluid in 9 of 9 children and was better than culture in patients who had received antibiotics (ICAAC D-1689, IDSA 331, 332).

The treatment of pneumococcal disease remains in a state of evolution. Twenty-four of 101 patients with S pneumoniae bacteremia were managed as outpatients, with therapeutic success in each case. Treatment of patients with pneumococcal bacteremia without meningitis caused by penicillin-nonsusceptible S pneumoniae with penicillin did not appear to adversely affect outcome. In vitro resistance is nonetheless meaningful. Of 13 children with invasive pneumococcal disease failing azithromycin therapy, 8 were infected with strains of S pneumoniae with the M phenotype, 3 with the MLSB phenotype, and 2 were macrolide susceptible. Among 15 with invasive pneumococcal infection, 7 were infected with penicillin-resistant strains, 4 with penicillin-intermediate strains, and 3 with penicillin-susceptible organisms (IDSA 251, ICAAC L-469, IDSA 793).

Mycoplasma pneumoniae

Serological testing, when compared to PCR identification, was not reliable in the diagnosis of lower respiratory tract infection due to M pneumoniae in hospitalized patients (ICAAC D-1860).

A single dose of azithromycin was at least as effective as the same total dose divided into 5 daily administrations in a murine model of M pneumoniae pneumonia; placebo was inferior to either regimen (ICAAC B-1672).

Chlamydia pneumoniae

The activities of telithromycin and levofloxacin were each increased against C pneumoniae in a cell coculture system in the presence of dexamethasone (ICAAC E-1994).

Legionella

The residential water system was identified as the probable source of infection in approximately one-fourth of cases of community-acquired L pneumophila serogroup 1 (ICAAC K-120).

Neisseria meningitidis

Review of national data led to the conclusion that, compared with sporadic infection, outbreaks of meningococcal disease had a higher case fatality rate (21% vs 11%; P < .001) (IDSA 289).

A 6-year-old sibling of a child who died of infection due to a rifampin-susceptible strain of N meningitidis developed meningococcemia due to a rifampin-resistant strain within a day of completing rifampin prophylaxis (IDSA 739).

Bordetella pertussis

Primary immunization with the Biken DTaP was found to have an efficacy of 96% against typical B pertussis disease with paroxysmal cough of > 21 days, with persistent protection for at least 5-7 years (ICAAC G-2050).

Some reports have indicated that symptoms considered characteristic of pertussis are uncommonly observed in adults. However, in an outbreak of pertussis in adult oil refinery workers, 90% had a paroxysmal cough, one-quarter had an inspiratory whoop, and one-quarter had post-tussive vomiting. Administration of a 5-day course of azithromycin was effective in the rapid eradication of B pertussis in adults, but persistent cough after treatment remained a cause of considerable morbidity and loss of work productivity (ICAAC L-1583, G-458).

Central Nervous System Infections

Bacterial Meningitis/Ventriculitis

Both host and bacterial factors are important in the outcome of pneumococcal meningitis. None of 20 patients with pneumococcal meningitis due to serotype 1 organisms died, while 27% of those with serotype 3 and 33% with serotype 9 did so. Impaired mental status on admission and delayed antibiotic administration (> 6 hours) were independent risk factors for death among 123 adults with pneumococcal meningitis (ICAAC L-613s, L-614).

Adjuvant doxycycline administration in a rodent model of pneumococcal meningitis was associated with improved survival and reduced neuronal injury when compared to treatment with ceftriaxone alone. This may be the result of inhibition of matric metalloproteinases, which have been associated with the pathogenesis of bacterial meningitis (ICAAC B-326).

A retrospective review found that 29 of 230 (12.6%) patients with an external CSF drainage device not receiving antibiotic prophylaxis developed bacterial meningitis, 72% due to Gram-positive organisms. The median time to onset was day 5 (range, 1-17). Increased risk of infection was associated with prolonged presence of the device and of CSF leakage. There were no associated deaths. The authors conclude that "prophylactic use of antibiotics is not indicated, provided that frequent CSF analysis is performed" (ICAAC K-577).

Two patients with external drainage device-related ventriculitis due to multidrug-resistant Gram-negative bacilli were successfully treated with intraventricular polymyxin B (IDSA 330).

Viral Encephalitis

Coronavirus OC43 was detected by PCR in CSF and nasopharyngeal secretions, in association with a 4-fold rise in antibody titer to the virus, in a patient with acute disseminated encephalomyelitis (IDSA 836, ICAAC V-173).

In an analysis of 27 patients with CNS West Nile virus infection, 14 had encephalitis, 7 had a Guillain-Barré-like syndrome, and 6 had aseptic meningitis. Seven patients had elevated CPK. EMG was abnormal in 12 of 13 patients. Six patients required mechanical ventilation, and 1 died (IDSA 837).

Bartonella Encephalopathy

Eighteen patients with serologically diagnosed cat scratch encephalopathy were identified between 1998 and 2002 in ongoing studies in Tennessee and California, representing 1.9% of encephalitis cases. The median age was 9 years (range, 4-40 years), and two-thirds had recent or concurrent lymphadenopathy. Seventy-two percent had peripheral leukocytosis. CSF in each case had normal WBC and glucose, while 39% had elevated protein. Brain imaging was normal in all but 1 case. PCR was unable to detect evidence of B henselae or B quintana in all 18 patients (IDSA 103).

Borrelia burgdorferi

A comparison of 24 children with meningitis due to B burgdorferi and 151 with enteroviral meningitis found that the former was associated with a longer duration of symptoms prior to presentation. Cranial neuropathy and papilledema were seen only in children with Lyme meningitis. The presence of > 10% neutrophils in CSF had a negative predictive value of 99% for the diagnosis of Lyme meningitis (IDSA 804).

Amebic Meningoencephalitis

Four children in North Texas died of amebic meningoencephalitis due to Naegleria fowleri after swimming in warm shallow waters during periods of drought. Two children in Arizona died of primary amebic meningoencephalitis within 24 hours of each other. It was discovered that both children had engaged in activities that may have led to nasal entry of ameba-contaminated water from the municipal water system, which was not required to chlorinate or filter. N fowleri was isolated from that water supply. A recent case of fatal primary amebic meningoencephalitis had been described in some detail by the CDC (MMWR Morb Mortal Wkly Rep. 2003;52:962) (IDSA 755, 748).

Tetanus

One hundred and twenty patients with tetanus were given human antitetanus immunoglobulin intramuscularly and were randomized to also receive it intrathecally or not. Intrathecal administration was associated with significantly better outcomes (ICAAC L-179).