Rifampicin-resistant Mycobacterium tuberculosis

of MDR TB during therapy in our patient was due to initial coinfection with two wholly different strains (one drug-sensitive and one MDR). Presumably, the MDR strain had been overgrown by the prevailing sensitive strain and thus been missed in the initial resistance testing. Our findings lend support to Glynn and colleagues’ hypothesis that mixed-strain infections do occur. Probably the true prevalence of mixed-strain TB infections is underestimated because of the difficulties of culturing two different strains from the same specimen. DNA fingerprinting allows the differentiation of mixed infection from acquired resistance during treatment. We recommend repeated resistance testing, especially in patients with delayed response to therapy and in those who originate from high prevalence areas for MDR TB. that the

This

occurrence

*A Theisen, C Reichel, S Rüsch-Gerdes, W H Haas, J K Rockstroh, U Spengler, T Sauerbruch

S!R—Rifabutin,

rifamycin derivative, has prophylaxis against Mycobacterium a

as

been avium

complex (MAC) for individuals with AIDS and CD4 T-cell counts of 100/L or below.’2 Public health officials are concerned that prophylaxis with rifabutin alone might lead to rifamycin resistance in M tuberculosis (necessitating prolonged therapy for tuberculosis [TB]), if TB disease is not adequately ruled out before rifabutin is used.’ We report a case of TB involving M tuberculosis resistant to rifampicin and rifabutin, which apparently evolved from a drugsusceptible strain after 6 months of rifabutin prophylaxis against MAC. A 30-year-old prison inmate, seropositive for HIV and with no previous history of TB, had three annual tuberculin skin tests measuring zero mm in the years 1990-92; anergy was demonstrated in 1993. In June, 1993, he had a CD4 Tcell count below 100/RL. No symptoms suggestive of TB were found on clinical examination; neither a chest nor sputum samples were obtained. Rifabutin of radiograph 300 mg per day was prescribed as prophylaxis against MAC. Compliance with this regimen was not recorded. Cough was first noted in December, 1993, and a sputum sample revealed M tuberculosis resistant to rifampicin and rifabutin. We suspect, but cannot prove, that the patient had been infected with a strain of M tuberculosis susceptible to rifampicin and rifabutin between January and February, 1993, at a New York State prison where he was incarcerated. During an investigation of a TB outbreak at that prison, we identified nine culture-positive TB cases with isolates susceptible to all first-line anti-TB drugs; all of the cases were associated with exposure to an index patient.4 Pvu-II/IS6110-based restriction fragment-length polymorphism (RFLP) analysis produced a single 1500 basepair band in M tuberculosis isolates from the nine drug-susceptible cases and this one case resistant to rifampicin and rifabutin. The clonal relation of the isolates was also suggested by RFLP analysis examining a 36 basepair direct-repeat sequencer The rifampicin-resistant isolate produced a fiveband pattern that matched four drug-susceptible isolates available for testing, which produced 5-7 bands each.

tuberculosis

resistant

to

*André C Weltman, Susan P Righi, George T DiFerdinando Jr, Robert J Jovell, Jeffrey R Driscoll Epidemic Intelligence Service and Division of Field Epidemiology, and Epidemiology Program Office, Centers for Disease Control and Prevention; *Bureau of Tuberculosis Control, New York State Department of Health, Albany, NY 12237, USA; and Wadsworth Center for Laboratories and Research, New York State Department of Health

3

tuberculosis recommended

M

to rule out the presence of active TB; include a chest radiograph and tuberculin "may skin test".2 Our case raises concerns about the appropriate use of rifabutin prophylaxis against MAC in populations at high risk of TB.

4

Rifampicin-resistant Mycobacterium

that

assessment

2

1 Haas WH, Butler WR, Woodley CL, Crawford JT. Mixed linker PCR: a new method for rapid fingerprinting of isolates of the Mycobacterium tuberculosis complex. J Clin Microbiol 1993; 31: 1293-98.

suggests

recommendations

1

*Department of General Internal Medicine, University of Bonn, 53105 Bonn, Germany, National Reference Centre for Mycobacteria, Borstel; and Department of General Paediatrics, University Children’s Hospital, University of Heidelberg

case

rifampicin can develop in patients receiving rifabutin alone as prophylaxis against MAC. Before beginning rifabutin clinicians should follow existing prophylaxis,

5

Nightingale SD, Cameron DW, Gordin FM, et al. Two controlled trials of rifabutin prophylaxis against Mycobacterium avium complex infection in AIDS. N Engl J Med 1993; 329: 828-33. US Public Health Service Task Force on Prophylaxis and Therapy for Mycobacterium avium complex. Recommendations on prophylaxis and therapy for disseminated Mycobacterium avium complex for adults and adolescents infected with human immunodeficiency virus. MMWR 1993; 42 (RR-9): 14-20. Reichman LB, McDonald RJ, Mangura BT. Rifabutin prophylaxis against Mycobacterium avium complex infection. N Engl J Med 1994; 330: 437-38. Weltman AC, Righi SP, DiFerdinando GT, Sullivan-Frohm AL, Jovell R. Drug-suceptible tuberculosis outbreak in the New York State prison system. American Thoracic Society Meeting, Boston, May 24, 1994 (abstr). van Soolingen D, de Haas PE, Hermans PW, Groenen PM, van Embden JD. Comparison of various repetitive DNA elements as genetic markers for strain differentiation and epidemiology of Mycobacterium tuberculosis. J Clin Microbiol 1993; 31: 1987-95.

Brain SPECT

findings in late whiplash

syndrome SiR-Some

patients with so-called whiplash syndrome have cognitive disturbances, especially in concentration and complex attentional processing. It has been speculated that these could be caused by drugs or by structural brain damage. Because of head restraints, whiplash injury today also produces a head impact that can lead to direct brain damage. In addition, experimental whiplash in monkeys can produce direct brain injury.’ Controlled and blinded studies in brain injury show that hexamethylpropyleneamine oxime single-photon emission computed tomography (HMPAOSPECT) detects more cerebral lesions than computed tomography or magnetic resonance imaging,2 and that SPECT shows abnormalities in patients with subjective complaints after mild head injury. We have investigated cerebral perfusion patterns by Tc99m-HMPAO-SPECT in over 100 patients with late whiplash syndrome 1 to 10 years after a car accident. From these patients we have analysed 28 patients in depth so far. These patients all had normal cranial computed tomography scans. They were compared with 15 normal control subjects. Two independent readers blinded to the clinical diagnosis could separate 24 of 28 patients from the normal control subjects. These 24 patients had at least unilateral and in most cases bilateral parieto-occipital hypoperfusion. None of the SPECT results from 15 normal control subjects was interpreted as abnormal. There were no clinical hints of other neurovascular or neurodegenerative disorders (eg, basilar artery migraine or Alzheimer’s disease) in any patient. In addition, we investigated patients with low back pain and with non-traumatic chronic cervical pain. Only 1 of 8 patients with low back pain had parieto-occipital perfusion irregularities, the remaining 7 being normal. Therefore the 3

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