Diagnosing TB: Are Fluoroquinolones a Problem?

Source: Dooley KE, et al. Clin Infect Dis. 2002;34:1607-1612.

Carol A. Kemper, MD, FACP

The widespread use of fluoroquinolones—which are quite active against Mycobacterium tuberculosis—for the treatment of community-acquired pneumonia (CAP) has led to concerns that, in some instances, a diagnosis of TB may be missed or delayed. Dooley and colleagues examined 33 recent cases of pulmonary TB diagnosed within the United States, 24 (73%) of whom were first treated for presumed CAP (12 received a fluoroquinolone as monotherapy, 4 received a fluoroquinolone plus another antibacterial, and 7 received an antibiotic other than a fluoroquinolone). Dooley and colleagues compared the outcomes of 16 patients (48%) who received fluoroquinolone with those who did not. The groups were nearly identical at presentation, with a similar frequency of cough, fever, sweats, weight loss, and radiographic findings (13% in each group had cavitary disease).

There was a significant delay in the diagnosis of TB and in the initiation of antituberculous therapy in patients receiving flouroquinolones compared with those who did not receive flouroquinolones (median, 21 vs 5 days; P = .04). Patients receiving fluoroquinolones were more frequently discharged before a diagnosis of TB was made (63%) compared with those who did not receive fluoroquinolones (29%). This occurred despite the fact that specimens for AFB smear and culture were obtained within a similar time-frame for both groups, and the frequency of smear-positive disease was similar (31% vs 47%; P > .20). This may have been due to the rapid clinical response to fluoroquinolone therapy observed in some patients: 83% of patients receiving fluoroquinolone monotherapy had significant clinical improvement within an average of 3 days.

An important concern, not addressed by this study, was whether the empiric use of fluoroquinolone therapy impairs the ability to diagnose pulmonary TB, especially in the event that adequate specimens for smear and culture are not collected at presentation. In addition, fluoroquinolones are an important component of therapy in patients with multi-drug resistant disease. While it is generally believed that a period of antibiotic exposure longer than the usual 10-14 days course of therapy for CAP is required to induce fluoroquinolone resistance, the widespread use of fluoroquinolones may eventually have a more global effect on the susceptibility of MTb to these agents.

VRSA Debuts in Michigan!

Source: Sievert DM, et al. MMWR Morb Mortal Wkly Rep. July 5, 2002.

This report describes the first clinical isolate of Staphylococcus aureus with high-level resistance to vancomycin (VRSA). The isolate was recovered from a 40-year-old diabetic with chronic renal failure on hemodialysis in Michigan. The patient had received multiple antibiotics (including vancomycin) for recurrent diabetic foot infections for about 1 year, when he developed MRSA bacteremia due to an infected arteriovenous graft. This infection was successfully treated with vancomycin and rifampin. Unfortunately, 2 months later, the patient developed a catheter exit site infection, cultures of which grew MRSA with high-level resistance to vancomycin (MIC > 128 mg/mL). One week later, cultures of a foot ulcer grew VRSA plus VRE. Both isolates remained sensitive to linezolid and quinupristine/dalfopristine.

Molecular studies confirmed that the S aureus isolate had acquired the vanA resistance gene, possibly from its neighboring VRE. Conjugative transfer of glycopeptide resistance genes from enterococci to S aureus has been demonstrated in vitro. S aureus isolates with low-level resistance to vancomycin have been popping up in many different countries, most recently England, but this is the first clinical isolate with evidence of the vanA gene.

Strict infection control practices have been instituted at the dialysis center, and, thus far, this appears to be an isolated case with no evidence of transmission. This sentinel case provides an opportunity to re-evaluate infection control practices at your center. While limiting transmission of these organisms is important, improved strategies to effectively decolonize patients chronically infected or colonized with MRSA should be explored—especially at dialysis centers where the reliance on vancomycin is so heavy. Sievert and associates also suggested that hospital laboratories should begin routinely performing MICs to vancomycin on MRSA isolates. 

Dr. Kemper, Clinical Associate Professor of Medicine, Stanford University, Division of Infectious Diseases; Santa Clara Valley Medical Center, is Associate Editor of Infectious Disease Alert.