Infectious Diseases: March 31, 2004

John Bartlett, MD

April 02, 2004

In This Article

Pneumonia and Other Respiratory Infections

Gauduchon V, Cozon G, Vandenesch F, et al. Neutralization of staphylococcus aureus Panton Valentine leukocidin by intravenous immunoglobulin in vitro. J Infect Dis. 2004;189:346-353. This is a report from Lyon, France designed to determine whether commercial intravenous immunoglobulin (IVIG) contains neutralizing antibody to Panton Valentine leukocidin (PVL). The interest is based on the assumption that PVL is responsible for pulmonary necrosis in necrotizing pneumonia due to Staphylococcus aureus. The investigators tested for specific anti-PVL immunoglobulin G (IgG) antibodies against recombinant PVL. They also measured cytotoxicity of purified PVL and culture supernatants of PVL positive S aureus strains by 2 methods: flow cytometry to determine effect on membrane pore formation and electron microscopy to demonstrate ultrastructural changes in polymorphonuclear leukocytes (PMNs). Test results showed that commercial IVIG contains PVL antibodies and neutralizes PMN pore formation and ultrastructural changes in PMN. The authors conclude that their studies justify a therapeutic trial of IVIG for necrotizing due to S aureus.

Comment: The Panton Valentine Leukocidin is a recognized virulence factor thought to be responsible for severe necrotizing pneumonia in previously healthy young adults. Characteristic clinical features include high fever, hypotension, hemoptysis, leukopenia, and multilobe infiltrates with a mortality of up to 75%.[1,2] Prior studies show that only 3-5% of S aureus strains produced PVL.[1,3] Interest in this topic has suddenly mushroomed as a result of an escalating epidemic of community-acquired infections due to a methicillin-resistant S aureus (MRSA) strain that often contains PVL. The major clinical expression is skin and soft tissue infections,[4] but some patients have invasive infections with pneumonia and/or bacteremia. It is emphasized that these strains are clonal, they are distinct from nosocomial MRSA, and they have a unique sensitivity pattern that consistently shows resistance only to beta-lactams. This strain is now being found with a frequency of 20-60% among S aureus isolates in many regions of the US, and epidemics have been reported in corrections, among some athletes, injection drug users, gay men, and aboriginals in Australia. Perhaps more importantly, this strain seems to be becoming endemic in many geographic regions. The suggestion is that a trial of IVIG should be enlisted in therapy based in part on the results of this study, the high mortality rate, and the prior studies showing failure to respond to antibiotic treatment.

Roson B, Fernandez-Sabe N, Carratala J, et al. Contribution of a urinary antigen assay (Binax NOW) to the early diagnosis of pneumococcal pneumonia. Clin Infect Dis. 2004;38:222-226. This is a report from Barcelona to determine the comparative value of the urinary antigen assay for Streptococcus pneumoniae vs sputum Gram stain for detection of this pathogen. The tests were compared in 220 patients with community-acquired pneumonia (CAP) who underwent evaluations for etiologic agents. The results were compared with a primary focus on the 41 patients who had culture evidence of S pneumoniae (blood or sputum cultures) and 27 who had a definitive test for an alternative pathogen. The results showed the urinary antigen assay was approximately 66% sensitive and 100% specific. Compared with Gram stain, the urinary antigen test was superior in sensitivity and both were 100% specific. The best results were obtained when both tests were done since this detected 40 of the 41 (98%) with culture evidence of S pneumoniae. The results are summarized in Table 1 .

The authors conclude that the urinary antigen test is relatively sensitive and specific, and permitted recognition of 26% more cases than Gram stain.

Comment: There is increasing interest in this test, in part relating to the general decline in microbiology studies. This reflects the combined effects of economics, Clinical Laboratory Improvement Amendments regulations, the outsourcing of microbiology, and the rush to complete the evaluation within the time frame allowed from registration to first dose of antibiotics, which is now 8 hours. At any rate, the urinary antigen test may now be the most practical way to obtain diagnostic information in patients with CAP. It appears to have reasonable sensitivity and good specificity on the basis of the data reported here as well as prior reports.[5,6] An additional advantage is that it retains sensitivity after administration of antibiotics.

Walsh EE, Peterson DR, Falsey AR. Risk factors for severe respiratory syncytial virus infection in elderly persons. J Infect Dis. 2004;189:233-238. The study involved 3 patient populations: (1) community-dwelling healthy persons over 65 years; (2) community-dwelling persons over 21 years with symptomatic cardiopulmonary conditions; and (3) persons over age 65 years or with underlying cardiopulmonary disease who were hospitalized with an acute respiratory illness. The study was done during the winter seasons of 1999-2000 and 2000-2001. It was prospective with enrolled subjects reporting respiratory illnesses that prompted an evaluation that included a nasopharyngeal swab. Respiratory syncytial virus (RSV) was confirmed by culture, serology, and reverse transcription polymerase chain reaction (RT-PCR). During the 2 seasons, there were a total of 130 RSV infections: 61 in the hospitalized group and 69 in the other 2 groups. The data showed RSV accounted for about 10% of respiratory tract infections (RTIs) as shown in Table 2 .

Risk factors for hospitalization due to RSV infection as determined by logistic-regression analysis of all RSV-infected patients are summarized in Table 3 that is restricted to those who prove to be statistically significant.

The most important factor was a low serum neutralizing antibody titer to RSV; other factors associated with the risk of hospitalization were age < 65 years, chronic pulmonary disease, and functional status. The authors concluded that their data potentially supports that an RSV vaccine could play an important role in reducing disease burden attributed to RSV in adults.

Comment: The association between severe infection with RSV in patients with chronic obstructive pulmonary disease is not surprising based on the analogy with influenza.[7] However, as pointed out by the authors here, there was not a significant risk associated with congestive failure, coronary artery disease, or diabetes. Particularly important was the inverse relationship between titers of neutralizing antibody and the risk of hospitalization with RSV infection. The most important message of the study was to emphasize the role of RSV as an important cause of morbidity and hospitalization, and the potential value of a preventive vaccine to boost.


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