Skip to main page content

• HOME
• Current Issue
• Archive
• Alerts
• About ASM
• Contact us
• Tech Support
• Journals.ASM.org

This Article Full Text (PDF) An erratum has been published Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Lopez-Aguilar, C. Articles by Aguirre-Jaime, A. Search for Related Content PubMed PubMed Citation Articles by Lopez-Aguilar, C. Articles by Aguirre-Jaime, A.

 Previous Article  |  Next Article 

Journal of Clinical Microbiology, January 2007, p. 274-276, Vol. 45, No. 1
0095-1137/07/$08.00+0     doi:10.1128/JCM.02032-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

LETTER TO THE EDITOR

Association between the Presence of the Panton-Valentine Leukocidin-Encoding Gene and a Lower Rate of Survival among Hospitalized Pulmonary Patients with Staphylococcal Disease

Top LETTER REFERENCES

 
Staphylococcus aureus is responsible for more than 2% of cases of community-acquired pneumonia and 10% of cases of nosocomial-acquired pneumonia. The lethality rate of such infections ranges from 30% to 80% (6). These infections are complicated by the fact that these bacteria have acquired diverse genetic information that makes them resistant to most antibiotics. Methicillin-resistant S. aureus (MRSA) is the most common cause of serious hospital-acquired infections (1). Infections of the respiratory tract by S. aureus can be more severe if the infecting strain produces the Panton-Valentine leukocidin (PVL) (9). The serious impact of PVL-positive S. aureus infections seems to be associated with pulmonary complications.

We hypothesized that PVL-positive MRSA is associated with mortality in patients with S. aureus pneumonia. During a period of 12 months, all of the hospital-acquired MRSA isolates recovered from individual patients in the pulmonary ward at the NS Candelaria University Hospital were included in this study. MRSA isolates were considered hospital acquired if they were recovered from a specimen collected 72 h or more after admission to the hospital. A collection of 24 MRSA isolates was characterized by different molecular techniques (3, 7, 8). Cases were analyzed to assess the association between PVL and death in patients affected by different pulmonary diseases and comorbidity charge summarized in the modified Charlson combined index (2). Computerized tomography analysis was also performed when necessary. The concordant diagnosis of pneumonia was determined by chart review by two independent, blinded pulmonologists. Pneumonia or bronchitis was defined by signs and symptoms of lower respiratory tract infection and chest radiography. After detection of MRSA, antibiotic treatment was guided by the antibiotic susceptibility results generated with the Vitek 2 system (bioMérieux, Lyon, France) and according to the guidelines of the Clinical Laboratory Standards Institute (5). Generally, antibiotic treatment comprised a macrolide with an expanded-spectrum cephalosporin or a quinolone. For other pathologies, treatments were applied according to internationally approved medical standards.

The following data were recorded for each patient: age, gender, arterial oxygen pressure and oxygenation rate value (ORV; arterial oxygen pressure divided by percent O₂ inhaled) at admission, length of hospital stay from MRSA detection to discharge or exitus, pulmonary disease (bronchitis or pneumonia), main declared reason for death as the principal or most important cause of death, comorbidity modified Charlson combined index, sample type for microbiological analysis, MRSA clone, and PVL presence. Although the sample size is a constraint of this study, the number of patients in the sample guarantees a power of 80% to detect differences as small as 45% between groups in two-tailed tests at a statistical significance level of P < 0.05.

Out of 24 patients included in this study, 14 died within 30 days after recovery of the MRSA isolate. Table 1 shows the measured parameters for dead and living patients. The presence of PVL differed significantly between dead and living patients, since all of the PVL-positive patients died. Table 2 shows the measured parameters in patients with PVL-positive or PVL-negative isolates of MRSA. The difference in the percentage of deaths between PVL-positive (100%) and PVL-negative (47%) patients reached statistical significance. A noteworthy hematological finding was the average trough leukocyte and lymphocyte counts, which differed significantly between PVL-positive and PVL-negative patients. Interestingly, the leukocyte level was over the reference range for PVL-positive patients but lymphocytes were under the reference range. Although some studies have shown that PVL-positive S. aureus isolates frequently cause hemorrhagic and necrotizing pneumonia, this was not found in this population (4, 10). As shown in Table 2, the in-hospital survival time was substantially less for PVL-positive patients and this difference reached statistical significance. The presence of the PVL gene increased the risk of death 1.56-fold (95% confidence interval: 1.06 to 2.30). The five isolates recovered from PVL-positive patients belonged to the ST125-IVA MRSA clone. PVL-negative ST125-IVA MRSA isolates were also detected in hospitalized patients without pulmonary MRSA infections during the same period of time, showing that this clone does not always harbor the PVL gene (data not shown).

View this table: [in this window] [in a new window]

TABLE 1. Living- versus dead-patients parameters

View this table: [in this window] [in a new window]

TABLE 2. Characteristics of PVL-positive versus PVL-negative patients

Figure 1 represents Kaplan-Meier curves of in-hospital survival at 30 days for patients with PVL-positive and -negative MRSA isolates. These curves pointed out the abrupt decrease in survival in the PVL-positive patients compared to a slower death rate in the PVL-negative patients. Survival showed an abrupt decrease in the presence of PVL, indicating that carriage of a PVL-positive S. aureus strain may be critical to death for pulmonary patients.

View larger version (10K): [in this window] [in a new window]

FIG. 1. Kaplan-Meier curves of cumulative survival at 30 days with PVL as a factor. The median (25th to 75th percentile) survival time, in days, was 30 (9 to 30) for PVL-negative patients versus 14 (9 to 29) for PVL-positive patients.

The findings of this study may have some implications for clinical decision making. PVL-positive MRSA strains seem to be dangerous for pulmonary patients, so we recommend screening for the presence of PVL when an MRSA is detected in such patients. If the presence of a PVL-positive MRSA strain is confirmed, antibiotic treatment should be reinforced to ensure elimination of the bacteria. An antibiotic to which resistance has not yet become a problem and with first-rate tissue distribution such as, for example, linezolid should be administered. Concomitantly, the spread of PVL-positive strains to other patients could have such deleterious consequences that we also recommend the isolation of patients with PVL-positive MRSA to prevent spread of the organism. However, further studies are necessary to prove the validity and applicability of these findings.

 
We are grateful to J. P. de Torres for critical reading of the manuscript.

This study was partially supported by grants FUNCIS 02/38 and MEC BIO2002/00953, Spain, to S.M.-A. S.M.-A. was partially supported by Public Health Research Foundation (FIS) grant 99/3060, Spain. E.P.-R. and C.L.-A. were partially supported by grants from Consejería de Educación, Cultura y Deportes, and FUNCIS, respectively, Gobierno de Canarias, Spain.

 
Published ahead of print on 8 November 2006.

Top LETTER REFERENCES

 

1
1. Berger-Bächi, B. 2002. Resistance mechanisms of gram-positive bacteria. Int. J. Med. Microbiol. 292:27-35.[CrossRef][Medline]
2
2. Charlson, M., T. P. Szatrowski, J. Peterson, and J. Gold. 1994. Validation of a combined comorbidity index. J. Clin. Epidemiol. 47:1245-1251.[CrossRef][Medline]
3
3. Enright, M. C., N. P. Day, C. E. Davies, S. J. Peacock, and B. Spratt. 2000. Multilocus sequence typing for characterization of methicillin-resistant and methicillin-susceptible clones of Staphylococcus aureus. J. Clin. Microbiol. 38:1008-1015.[Abstract/Free Full Text]
4
4. Gillet, Y., B. Issartel, P. Vanhems, J. C. Fournet, G. Lina, M. Bes, F. Vandenesch, Y. Piemont, N. Brousse, D. Floret, and J. Etienne. 2002. Association between Staphylococcus aureus strains carrying gene for Panton-Valentine leukocidin and highly lethal necrotising pneumonia in young immunocompetent patients. Lancet 359:753-759.[CrossRef][Medline]
5
5. National Committee for Clinical Laboratory Standards. 2003. Performance standards for antimicrobial disk susceptibility tests, 8th ed. Approved standard M2-A8. National Committee for Clinical Laboratory Standards, Wayne, PA.
6
6. Obed, A., A. A. Schnitzbauer, T. Bein, N. Lehn, H. J. Linde, and H. J. Schlitt. 2006. Fatal pneumonia caused by Panton-Valentine leukocidin-positive methicillin-resistant Staphylococcus aureus (PVL-MRSA) transmitted from a healthy donor in living-donor liver transplantation. Transplantation 81:121-124.[CrossRef][Medline]
7
7. Pérez-Roth, E., F. Claverie-Martín, J. Villar, and S. Méndez-Álvarez. 2001. Multiplex PCR for simultaneous identification of Staphylococcus aureus and detection of methicillin and mupirocin resistance. J. Clin. Microbiol. 39:4037-4041.[Abstract/Free Full Text]
8
8. Pérez-Roth, E., F. Lorenzo-Díaz, N. Batista, A. Moreno, and S. Méndez-Álvarez. 2004. Tracking methicillin-resistant Staphylococcus aureus clones during a 5-year period (1998 to 2002) in a Spanish hospital. J. Clin. Microbiol. 42:4649-4656.[Abstract/Free Full Text]
9
9. Robinson, D. A., A. M. Kearns, A. Holmes, D. Morrison, H. Grundmann, G. Edwards, F. G. O'Brien, F. C. Tenover, L. K. McDougal, A. B. Monk, and M. C. Enright. 2005. Re-emergence of early pandemic Staphylococcus aureus as a community-acquired methicillin-resistant clone. Lancet 365:1256-1258.[CrossRef][Medline]
10
10. Vandenesch, F., T. Naimi, M. C. Enright, G. Lina, G. R. Nimmo, H. Heffernan, N. Liassine, M. Bes, T. Greenland, M. E. Reverdy, and J. Etienne. 2003. Community-acquired methicillin-resistant Staphylococcus aureus carrying Panton-Valentine leukocidin genes: worldwide emergence. Emerg. Infect. Dis. 9:978-984.[Medline]

						C. Lopez-Aguilar E. Perez-Roth S. Mendez-Alvarez* Molecular Biology Laboratory Unidad de Investigación Hospital Universitario NS Candelaria Ctra. del Rosario 100 38010 Santa Cruz de Tenerife, Spain A. Moreno Microbiology Service Hospital Universitario NS Candelaria 38010 Santa Cruz de Tenerife, Spain M. C. Duran Internal Medicine Service Hospital Universitario NS Candelaria 38010 Santa Cruz de Tenerife, Spain C. Casanova Pneumology Department Hospital Universitario NS Candelaria 38010 Santa Cruz de Tenerife, Spain A. Aguirre-Jaime Research Support Service Hospital Universitario NS Candelaria 38010 Santa Cruz de Tenerife, Spain
						* Phone: 34-922-600080, Fax: 34-922-600562, E-mail: smenalv{at}gobiernodecanarias.org

---

Journal of Clinical Microbiology, January 2007, p. 274-276, Vol. 45, No. 1
0095-1137/07/$08.00+0     doi:10.1128/JCM.02032-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

This article has been cited by other articles:

• Nathwani, D., Morgan, M., Masterton, R. G., Dryden, M., Cookson, B. D., French, G., Lewis, D., on behalf of the British Society for Antimicrobial, (2008). Guidelines for UK practice for the diagnosis and management of methicillin-resistant Staphylococcus aureus (MRSA) infections presenting in the community. J Antimicrob Chemother 61: 976-994 [Abstract] [Full Text]  

This Article Full Text (PDF) An erratum has been published Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Lopez-Aguilar, C. Articles by Aguirre-Jaime, A. Search for Related Content PubMed PubMed Citation Articles by Lopez-Aguilar, C. Articles by Aguirre-Jaime, A.