Commentary (Hughes): Infectious Complications of Lung Cancer

The stated aim of Seo's article is to focus on the diagnosis and management of infections that can occur in patients with lung cancer. Most of the studies of infections in cancer patients over the past 4 decades have dealt predominantly with opportunistic infections in immunocompromised individuals who have lymphoproliferative malignancies. Less attention has been given to infections associated with solid tumors, so a comprehensive review of the problem in patients with lung cancer is greatly needed. Unfortunately, the number of detailed and controlled studies specifically addressing infectious complications in lung cancer patients is limited. The author reviews the relevant studies reported over the past 20 years. Furthermore, she utilizes information and experience gained from studies of patients with lymphoproliferative malignancies, AIDS, and other immunocompromised hosts. The comments and recommendations made in this review represent a reasonable approach to the management of infections in patients with lung cancer. Many of the recommendations for treatment parallel the cited guidelines prepared by expert panels of the Infectious Diseases Society of America, including those for community-acquired pneumonia in adults (Seo's reference 33), candidiasis (reference 24), and antimicrobial agents in neutropenic patients with cancer (reference 19), reflecting a consensus of infectious diseases specialists. Studies of Infections in Lung Cancer
A couple of recent studies dealing specifically with infections in lung cancer patients are of interest and expand the perspective of Seo's work. Insight into the cause and timing of postoperative infections comes from a prospective study of 194 patients operated on for lung cancer. Sok et al[1] sought to identify pathogens by the use of intraoperative swabs and sputum samples for cultures taken before, during, and 3 days after the surgery. Documented infections occurred in 34 patients-32 were classified as pleuropulmonary and 2 were from wounds. Approximately 75% of the infections were caused by gramnegative bacteria and Candida albicans. The postoperative sputum specimens were most predictive of the cause of the infection (P < .01), suggesting that organisms that cause pleuropulmonary infections are probably acquired postoperatively from the patient's oral cavity and upper respiratory tract. An interesting observation on the association of Pneumocystis carinii infection and small-cell carcinoma of the lung was reported by de la Horra et al[2] in 2004. Using a polymerase chain reaction assay to identify the presence of P carinii DNA, they examined lung tissue sections from 10 cases of small-cell lung cancer (SCLC), 10 cases of non-small-cell lung cancer (NSCLC), 5 cases with normal lungs, and 2 cases of P carinii pneumonia. P carinii DNA was found in all cases of SCLC, in 2 of 10 NSCLC cases, 2 of 2 P carinii pneumonia cases, and none of the 5 control cases, suggesting an association between subclinical P carinii infection and SCLC. No standard guidelines have been established for the use of chemoprophylaxis for P carinii pneumonia in patients with lung cancer. Drug Dosage
One troublesome point on therapy is the dose of trimethoprim (TMP)- sulfamethoxazole (SMZ) that Seo recommends for the treatment of P carinii (use of the term "Pneumocystis jiroveci" is controversial[3]) pneumonia. The author gives a dose based on 15 to 20 mg TMP per kg per day (plus 75 to 100 mg SMZ per kg per day). It should be noted that this is the dose for children, whereas the doses of all other drugs in the article are for adults. This is a mistake sometimes made in practice resulting in a significant overdosage that may be associated with adverse effects. The problem stems from the fact that the original studies of TMPSMZ for the treatment of P carinii pneumonia that led to Food and Drug Administration (FDA) approval were done in children, so the leaflet insert gave the dosage based on body weight. Calculation of adult doses from pediatric doses based on body weight may be hazardous. For example, the dose for a 70-kg man recommended in this paper would be 1,050 to 1,400 mg TMP and 5,250 to 7,000 mg SMZ per day. The current FDA-approved dose for the treatment of P carinii pneumonia in adults is 320 mg TMP and 1,600 mg SMZ per day. Thus, the dose mentioned in Seo's article is three to four times the appropriate dose and may be associated with adverse effects. The doses of pentamidine, based on body weight, and trimetrexateleucovorin, based on body surface area, are satisfactory because they are based on studies done in adults using body size for dose determination. Conclusion
Dr. Seo discusses standard approaches to the diagnosis and management of the infections generally encountered in patients with cancer. Further research is needed to focus on infections unique to the patient with lung cancer.

Disclosures:

The author has no significant financial interest or other relationship with the manufacturers of any products or providers of any service mentioned in this article.

References:

1. Sok M, Dragas AZ, Erzen J, et al: Sources of pathogens causing pleuropulmonary infections after lung cancer resection. Eur J Cardiothorac Surg 22:23-27, 2002.
2. De la Horra C, Varela JM, Fernandez- Alonso J, et al: Association between human Pneumocystis infection and small cell carcinoma. Eur J Clin Invest 34:229-235, 2004.
3. Hughes WT. Pneumocystis carinii vs Pneumocystis jiroveci: Another misnomer. Emerg Infect Dis 9:276-277, 2003.