Multidrug-resistant tuberculosis in pregnancy: Case report and review of the literature
Multidrug-resistant tuberculosis in pregnancy: Case report and review of the literature
| Multidrug-resistant tuberculosis in pregnancy: Case report and review of the literature |
| Klaus-Dieter K L Lessnau, Samer Qarah. Chest. Chicago: Mar 2003.Vol.123, Iss. 3; pg. 953, 4 pgs |
| Author(s): | Klaus-Dieter K L Lessnau, Samer Qarah |
| Publication title: | Chest. Chicago: Mar 2003. Vol. 123, Iss. 3; pg. 953, 4 pgs |
| Source type: | Periodical |
| ISSN: | 00123692 |
| ProQuest document ID: | 316477691 |
| Text Word Count | 2280 |
| Document URL: | http://proquest.umi.com/pqdweb?did=316477691&sid=5&Fmt=4&clientId=45625&RQT=309&VName=PQD |
| Full Text (2280 words) | |||||||||||||||||||||||||||||||||||||||||
Copyright American College of Chest Physicians Mar 2003
Cavitary multidrug-resistant (MDR) tuberculosis (TB) [ie, TB that is resistant to at least rifampin and isoniazid] during pregnancy is rare. Published data are absent, although streptomycin is known to be teratogenic with about one of six fetuses developing cranial nerve VIII palsies or deafness. Additional second-line drugs have been classified as category C (ie, uncertain safety, and no human or animal studies show an adverse effect). Some physicians would consider offering abortion counseling in a pregnant woman with culture-proven MDR-TB because the medications used to treat patients with MDR-TB may be fetotoxic or may have not been studied adequately for their safety to be guaranteed during pregnancy.1,2 Agents needed for treatment may be toxic to mother and fetus, and the risks of treatment should be assessed accordingly.3 We report a case of a pregnant woman who refused an abortion, received four second-line drugs for the treatment of MDR-TB, and delivered a healthy neonate. We review all reported cases of MDR-TB during pregnancy. CASE REPORT A 22-year-old gravid African-American woman was evaluated at 23 weeks' gestation during her second pregnancy because of a positive tuberculin skin test result with 18 mm of induration. The patient reported a history of dry cough and fever for 2 months, and weight loss and night sweats for 1 month. She denied hemoptysis. The findings of her physical examination were unremarkable except for a body weight of 48 kg (body mass index, 18.3 kg/m^sup 2^). On examination, her temperature was 42 degC. Breath sounds were normal, and there were no crackles, rales, or rhonchi. The patient was admitted to the hospital. The chest radiograph revealed a left upper lung cavity (Fig 1). Additional infiltrates could be seen in the entire left lung and in the right parahilar mid-lung field. Several concentrated sputum samples revealed numerous acid-fast bacilli. Daily antituberculous therapy was initiated with rifampin, 600 mg, isoniazid, 300 mg, and ethambutol, 700 mg (with a target of 15 ing/kg). One smear-positive specimen was immediately processed for susceptibility testing after communicating with the mycobacteriology laboratory. After 3 weeks of treatment, the patient continued to have a temperature of up to 39.4 deg C and experienced a weight loss of about 5 kg. A repeat chest radiograph revealed a worsening of the left lung infiltrate and a persistence of the right-sided infiltrate. Preliminary sputum results obtained from the mycobacteriology laboratory suggested resistance to the three drugs used and to streptomycin. The patient was counseled about therapeutic abortion but refused despite information about the potentially toxic effects of the drugs on the fetus. Empirical treatment was started as follows: capreomycin, 100 mg as IV infusion for > 2 h 5 days per week; oral cycloserine, 500 mg in the morning and 250 mg in the evening; oral levofloxacin, 1,000 mg daily; and oral para-aminosalicylic acid granules, 4 g three times per day, occasionally mixed in apple sauce. After receiving positive susceptibility results, pyrazinamide, 1,500 mg/d, was added as a fifth drug for treatment. The patient was treated for 8 weeks. Her membranes ruptured spontaneously at 35 weeks' gestation. Terbutaline therapy was added for induction. A healthy infant weighing 2,003 g was delivered vaginally. The newborn was separated from the mother. The placenta was normal on pathology examination. The infant's tuberculin skin test and three nasogastric aspiration cultures were negative for TB. A neurologic examination and electrophysiologic hearing studies of the infant were normal. The baby continued to thrive, and therefore a lumbar puncture was not performed. Following delivery, the patient continued to receive the main drug, capreomycin, 1,000 mg 5 days per week as IV infusion. The drugs that were used to prevent resistance against capreomycin included para-aminosalicylic acid granules, 4,000 ing po three times per day, pyrazinamide, 1.5 g per day, and cycloserine, 500 mg in the morning and 250 mg in the evening with 200 mg vitamin B, daily. Therapy with ethionamide (500 mg po in the morning and 250 mg in the evening) was added, and levofloxacin therapy was changed to daily therapy with moxifloxacin, 400 mg. The administration of these six drugs was continued because of slow fever resolution, continued weight loss, and sputum smear positivity for > 8 weeks. No adverse effects from the second-line medication were noted. The results of monthly audiometry remained normal, and liver function tests showed only a onefold increase in transaminase levels. Additional consecutive sputum samples were tested at the New York City Department of Health, Bureau of Laboratories, and the tests confirmed the susceptibility pattern of the first specimen. The patient was discharged from the hospital after three consecutive concentrated sputum smears converted to a negative result. Directly observed therapy was continued twice daily 5 days per wk. The total treatment time was scheduled to be 18 months after the documented conversion of monthly sputum cultures to negative for TB. The patient refused directly observed therapy by a public health adviser. After a public health commissioner issued an order for directly observed therapy and a possible detention order was issued, the patient opted to continue observed treatment. The child remained separated from the mother until her sputum cultures converted to negative. Therefore, vaccination with bacillus CalmetteGuerin was not indicated as its effectiveness has not been proven and because bacillus Calmette-Guerin vaccination would interfere with tuberculin skin testing.
Interestingly, the patient's mother was -also known to have had MDR-TB. Nine years earlier, she had worked in health care during an MDR-TB outbreak among hospitalized AIDS patients. DiSCUSSION Recommendations for the treatment of pregnant women with pulmonary TB are provided by the New York City Department of Health2 and the American Thoracic Society.4 However, guidelines are not available for the treatment of patients with MDR-TB during pregnancy. The natural history of TB was studied in 250 pregnant women with 370 pregnancies prior to the advent of effective treatment.5 None of the women died during pregnancy, but 24 spontaneous abortions (6.5%) occurred. None of the infants developed congenital TB, and cervical TB was diagnosed in one pregnant woman. Although the literature reports > 176 cases of congenital TB,6 the prevalence is <> In 1981, 16 pregnant women were reported to have isoniazid-resistant TB.7 All were treated with first-line medications and para-aminosalicylic acid during pregnancy. One patient had a spontaneous abortion after 4 months of pregnancy. After birth, one infant died of miliary TB at 3 months, and one infant died of meningeal TB. Another infant developed pulmonary TB from inhalation at 6 months. The 12 remaining pregnancies had positive outcomes. However, none of the isoniazid-- resistant isolates was tested for rifampin resistance. Five cases of documented MDR-TB in pregnant women were located in the literature.8,9 Only one of these five patients was treated with a second-line drug (ethionamide), in addition to pyrazinamide and rifampin. This patient did not develop adverse effects from three-drug therapy, and the neonate was healthy. Two patients were untreated during gestation. One patient had a therapeutic abortion, and the other received therapy with rifampin and isoniazid for MDR-TB (so-called "holding therapy"). An additional sixth pregnant woman with isoniazid/ pyrazinamide-resistant Mycobacterium bovis infection was treated with rifampin, isoniazid, and ethambutol only.10 Therapy with streptomycin was added after delivery, and a second-line medication was not administered. The treatment for our patient was more complicated. The patient refused therapeutic abortion. Her cavitary TB worsened on chest radiograph, and her sputum smears remained strongly positive for TB, suggesting MDR-TB. Treatment was clearly indicated to curtail weight loss; to terminate a source of transmission; to avoid dissemination, mycobacteremia, meningitis, or death for the mother; to decrease the risk of congenital TB; to protect the healthcare workers in the delivey room; and to decrease the separation time between mother and newborn. The socalled holding therapy was inappropriate in our patient after preliminary results of direct susceptibility plating that suggested resistance. A worsening chest radiograph on treatment is another hallmark of resistance.11 It was necessary to start all available, relatively weak, second-line drugs to avoid having the patient develop resistance against capreomycin. Ethionamide was avoided because it causes birth defects and spontaneous abortion in high doses in animals.17 Levofloxacin has been used more often than moxifloxacin as therapy in adults and infants with MDR-TB. After delivery, treatment with levofloxacin was changed to moxifloxacin, which may be more active against Mycobacterium tuberculosis. Although only animal data exist at this time, and there is no published evidence about its improved efficacy in humans, it was used in this patient to replace levofloxacin, as suggested by the New York City Department of Health, Bureau of Tuberculosis Control.12 Capreomycin therapy, 5 days per week2 did not cause hearing defects in mother or neonate. The incidence of ototoxity from capreomycin therapy is unknown, although streptomycin was found to cause hearing impairment in one of six infants treated.13 Pyrazinamide is currently not recommended as a first-line drug for the treatment of TB during pregnancy in the United States, but it has been used safely in other countries without evidence of birth defects. Although it has been stated that untreated TB has a spontaneous abortion rate of 2.9% and treated TB has an abortion rate of 2.2%,6 it would require 16,486 randomized patients to prove a statistically significant difference. 14 Obviously, such a study would not be feasible. CONCLUSION The clinician must weigh the risk of dissemination in neonate and mother (about 1 to 2% for the mother) vs the risk of adverse effects from the administration of second-- line medication. This case shows that a positive outcome for the neonate is possible with the use of second-line medication. Direct susceptibility testing of the first sputum sample was requested to decrease the turnover time for results. Conventionally, collected sputa are cultured on liquid and solid media. Once the growth of M tuberculosis is confirmed, subcultures are inoculated on susceptibility media. Susceptibility results are available once the subculture growth is observed. A reduction of half the turnaround time for susceptibility results is achieved if only one cycle is required instead of two. The identification of resistant TB strains will require only half the turnaround time. This issue is important for the clinical management of TB patients. In our case of a patient with thick-walled cavitary TB, there was a high clinical suspicion that the first specimen would be smear-positive and culture-positive for TB. Therefore, it was cost-effective to request immediate susceptibility testing. Close communication with the mycobacteriology laboratory was the key in decreasing the turnover time for susceptibilities by about 50%, which was useful to document early resistance and to manage the patient's condition appropriately.
|
No comments:
Post a Comment