x

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The mother, the fetus or both?

uberculostatic therapy
uberculostatic therapy

Abstract

Tuberculosis meningitis is a life-threatening disease that often challenges physicians, and more so in cases with immunosuppressed patients. Physiological immunosuppression due to pregnancy is a particular condition that poses increased risks. We present the case of a 19- year-old patient diagnosed with TB meningitis, with a 27-week-old pregnancy that has raised a series of ethical questions regarding medical intervention. The specific treatment for TB meningitis is considered to pose risks for foetal development. For this reason, the multidisciplinary team tending to this patient evaluated whether or not the pregnancy should be terminated, in the benefit of the mother’s health. The gynecologist's point of view was to maintain the pregnancy, all the more so as it evolved normally until the time of admission, with normal fetal morphology. The psychological report showed that the mother had a strong wish to keep the baby. So, after proceeding with therapy, the mother’s clinical and biological evolution was favorable, with the amendment of neurological symptomatology, recurrent appetite and weight gain. The pregnancy also evolved normally. Upon perceiving an improved condition, the mother insisted to be discharged from the hospital, thus determining the medical team to make further decisions regarding hospitalization, medication, and attitude towards the patient.

 

Tablet of Contents:

1. Case presentation

2. Discussions

3. Conclusions

 

1. Case presentation

In practice the infectious diseases physician sometimes encounters cases whose medical particularities, complemented by socio-emotional aspects, create ethical that require a thorough analysis of all possible implications.

We present the case of a 19-year-old patient who came on September 23, 2018 to the St. ParaschevaInfectious Diseases Clinical Hospital in Iaşi by transfer from Bacau Emergency Reception Unit. She had an evolutionary pregnancy of 27 weeks and reported low fever, headache, vomiting for the last 4 days. The young woman presented herself for 3 consecutive days in UPU Bacau, but doctors there consider the symptoms as manifestations of a more difficult pregnancy. Called at an inter-clinical consultation in UPU Bacau, the infectious physician raised the suspicion of a meningeal syndrome in a febrile context or meningitis and guided the patient to the Infectious Diseases Clinical Hospital in Iasi. Upon admission on September 23, 2018, the patient was conscious, but with intense headache, vomiting, refusal to eat and symptoms associated to early meningitis, as well as a discrete drop of the eyelid.

Inflammatory tests were altered, with an increased number of polymorphonuclear leukocytes, VSH=60 mm/h, normal liver and kidney tests, and normal blood ion count. The radiological pulmonary examination revealed opacity of uniform homogeneous lower right lobe. Initial third-generation cephalosporin antibiotic therapy was instituted, and lumbar puncture was performed. This revealed intense xanthochromia cerebrospinal fluid (CSF) with a number of 153 elements/mmc, 36% polymorphonuclear cells, high CSF chloride, and a low glycogen, with CSF albumin levels 16.8 g/l. Direct bacterioscopy and latex-agglutination for the major bacterial germs were negative.

The insidious onset of the disease, with the major change in the appearance and the biological constants of the cerebrospinal fluid, although without a tuberculosis evoking pulmonary radiological imaging, led us to a highly positive PCR for Mycobacterium tuberculosis. Immediate therapy with quadruple tuberculostatic association, dexamethasone in decreasing dose and broad-spectrum bactericidal antibiotic (meropenem) was initiated.

Meropenem was discontinued after 7 days, proving its efficacy, so that the radiologic pulmonary image was normal-normal radiologic pulmonary cord.

The problem at the time of diagnosis, under meningitis and tuberculostatic therapy, was whether to maintain the pregnancy or to extract the premature baby. Genital examination and ultrasound showed a normal appearance, according to gestational age, with re-evaluation 2 times a week. There were no fetal malformations.

Under therapy, clinical and biological evolution was favorable, with the amendment of neurological symptomatology, recurrent appetite and weight gain. Pregnancy also evolved normally, as genital examination and ultrasound revealed.

 

2. Discussions

This case involved an extremely serious, life-threatening illness in a 27-week-old pregnant woman, so it posed serious questions of medical ethics and implicitly human rights – the right to health for both the mother and the conception product. In medical practice and in medical law, saving the life of the patient, in this case of pregnant women, is a priority. Tuberculous meningitis is a serious condition with a high risk of death in immunosuppressed individuals [1, 2].

In the present case, immunosuppression is a physiological one in the context of pregnancy. Therapy implied, as the guidelines suggest, the association of four molecules over a 42-day period, first-line tuberculostatic but with high risk of hepatopathy [3]. This can endanger both the mother and the fetus, due to the major risk of drug-related hepatic failure [4, 5, 6].

Given the advanced stage of pregnancy, organogenesis in the fetus had already occurred and the consultation did not reveal malformations. So, it was necessary to assess the future impact that the mothers treatment will have on the fetus. The psychologists repeated discussions with the patient revealed that, being just married and having her husband abroad at work, she desired her child very much, invested emotionally in the pregnancy, and gave it the symbolic meaning of the couples love. Thus, the medical team had to explore ways of maintaining pregnancy health during the mothers treatment. The risk of hepatotoxicity was prevented by oral and intravenous hepatoprotective therapy [7].

The gynecologists point of view was to maintain the pregnancy, all the more so as the pregnancy had a normal evolution until the time of admission, with normal fetal morphology.

Evaluations were repeated twice a week, up to 31 weeks of pregnancy, and were less frequent later. The clinical progression of the patient was favorable, the eyelid drops resolved during the first 3 weeks of therapy, headache disappeared, appetite was regained, and the patient gained weight. Biologically, the cerebrospinal fluid had a favorable progression, CSF glucose gradually increasing and CSF protein gradually declining. The appearance of the liquid changed from intense to pale xanthocromic.

From a psychological point of view, the remittance of clinical symptoms had increased the patient’s psycho-emotional tone. Due to her age (19 years) and average level of education, she associated the subjective state of wellbeing with healing, and began to resent continuous hospitalization. She repeatedly requested discharge. Thus, a series of in-depth discussions with the infectious physician and the psychologist were needed, drawing attention to the possible consequences that premature discharge may have on both her health and her fetus.

According to Hippocrates’ oath, the medical team, having an overview of the disease and its evolution, has the duty and obligation to ensure health and to act according to medical guidelines, modulating and personalizing therapy according to the patients characteristics.

The medical recommendation in this case was to continue hospitalization, but the patient was reluctant to accept. Informative and persuasive discussions were necessary, and the patient was convinced to accept each time. This rather paternalistic attitude [8] of the medical team was entirely motivated by the attitude of the patient, as her major right to decisions about her own person came in conflict with the principle of both her wellbeing and the fetus’ welfare. Acting in respect for the patients autonomy, accepting unconditionally her decision to discharge, would have led to the decline of her health and, implicitly, the fetus’s. The medical team considered the principles of beneficence and non-maleficence [9], placing the right to life and health of two people (mother and fetus) above the patients right to choose discharge, which was actually motivated only by the emotional discomfort given by hospitalization [10].

 

3. Conclusions

This case was particularly provocative both due to the specificity of the life-threatening pathology and due to the patients characteristics. The medical team has acted according to its own beliefs and experience over time, also taking into account that the viability of the fetus and its health was of utmost importance to the patient. So, the decision was not to choose between the mother and the child, but to choose both.

The fact that this patient was tended to by not only the infectious diseases doctor, but also a gynecologist and a psychologist made monitoring and treatment vastly more efficient. Such a case, of particular complexity, can only be solved by a multidisciplinary team, dedicated, competent in the field and with the ability to analyze and predict evolution.

 

The Authors:

MANCIUC Doina Carmen [1]

LARGU Maria Alexandra [1]

[1] University of Medicine and Pharmacy Grigore T. Popa” Iași (ROMANIA)

REFERENCES

1. Tunkel, A. R., Van De Beek, D., Scheld, W. M. Acute Meningitis. In Mandell, Douglas, Bennetts

Principles and Practice of Infectious Diseases, 7th Ed., Elsevier 2008, pp. 1189-1231.

2. Hristea, A. et al., (2012). Characteristics of tuberculous meningitis in HIV-infected patients. Journal of the International AIDS Society, 15(Suppl. 4). http://www.jiasociety.org/index.php/jias/article/view/18413

3. Luca, M. C. et al., (2012). Tuberculousis-clinical and epidemiological considerations (a retrospective study 2008-2011). Rev Med Chir Soc Med Nat Iasi 116(3), pp. 746-749.

4. Luca, C. M. et al., (2005). Tuberculous meningitis in sucklings. Clinical Microbiology & Infection Supplement 11, p. 743.

5. Jana, N., Rakshit, B. M., Trivedi, G. (2008). Tuberculous meningitis in early pregnancy mimicking hyperemesis gravidarum: a diagnostic challenge. J Obstet Gynaecol 28(5), pp. 530-531. doi:

10.1080/01443610802249267.

6. Ezzouine, H., Charra, B., Benslama, A., Motaouakkil, S., Sodqi, M. (2008). A case of tuberculous meningitis in pregnancy. Med Mal Infect, 38(1), pp. 36-37. doi: 10.1016/j.medmal.2007.11.002.

7. Grünhage, F., Sauerbruch, T., Spengler, U. (2005). Tuberculosis – current therapeutic concepts. Dtsch Med Wochenschr 130(4), pp. 159-164.

8. Emanuel, E. J., Emanuel, L.L. (1992). Four Models of the Physician-Patient Relationship. JAMA, 267, 16, Research Library, p. 2221.

9. Beauchamp, T., Childress, J. Principles of Biomedical Ethics, 7th Edition. New York: Oxford University Press, 2013.

10. Kopecky, K. E., Urbach, D., Schwarze, M. L. (2018). Risk Calculators and Decision Aids Are Not Enough for Shared Decision Making. JAMA Surg, doi: 10.1001/jamasurg.2018.2446. [Epub ahead of print]