Guideline: Management of Drug-Resistant Tuberculosis » Monitoring and Evaluation of Patients with DR-TB
 

14. MONITORING AND EVALUATION OF PATIENTS WITH DR-TB

 

14.1. Introduction

 

MDR- or XDR-TB disease can be an emotionally devastating experience for patients and their families, while stigma related to the disease may interfere with adherence to treatment. In addition, the long duration of DR-TB treatment, combined with ADRs, may contribute to depression, anxiety and further jeopardise treatment adherence.

Monitoring the patient throughout the treatment period is therefore essential. The symptoms of DR-TB generally improve within the first few months of treatment. However, early resolution of symptoms is not an indication of cure, and recurrence of symptoms after sputum conversion may be the first sign of treatment failure. Laboratory evidence of improvement is therefore required, together with regular clinical assessment of the patient.

 

14.2. Monitoring Progress of Treatment

 

Patients on MDR- or XDR-TB treatment need to be monitored closely for side effects and signs of treatment failure. There are essentially three components to treatment monitoring namely, clinical, laboratory and other investigations.

 

14.2.1. Clinical Evaluation

The patient must be evaluated by the doctor weekly during the injectable phase and monthly during the continuation phase. Different scenarios need to be considered. During admission, regular medical ward rounds must be conducted. This may be every second day, twice a week or weekly for stable patients; nursing care must be provided daily and the patient record card updated. Patients who are very sick or critical need to be reviewed on a daily basis by the doctor.

A focused assessment of the patient should be conducted looking at any respiratory distress, gastro-intestinal disturbances, drug intolerance or ADRs, progression of hearing loss or tinnitus, and neuro-psychiatric effects. A physical exam should be conducted and routine laboratory tests or any other tests that may be indicated at the time.

Weight, height and body mass index (BMI) are also important parameters to monitor. Weight needs to be measured every week during injectable phase, then monthly during continuation phase. Height is to be measured at baseline while BMI need to be looked weekly during admission especially for patients with BMI<18.5.

14.2.2. Bacteriological Investigations

Culture and smear conversion are the most important indicators of patient improvement. Smear microscopy and bacteriological culture are therefore used to monitor patient progress throughout treatment and should be performed monthly. Microscopy is useful as a good indicator of patient progress; however, it cannot distinguish viable organisms from those that are non-viable. Culture is therefore necessary to monitor treatment progress. One sputum specimen should be sent monthly to the NHLS for smear microscopy and culture (not DST).

Definition of Conversion

Two types of conversion are considered for DR-TB patients (i.e., smear conversion and culture conversion); both require that the smear or culture be positive at the beginning of treatment.

  • Smear conversion is defined as two consecutive negative ‘smears’, taken at least 30 days apart. Time to conversion is calculated as the interval between the date of treatment initiation and the date of the first of the two negative consecutive smears (the date of sputum specimen collection should be used).
  • Culture conversion is defined as two consecutive negative ‘cultures’, taken at least 30 days apart. Time to conversion is calculated as the interval between the date of treatment initiation and the date of the first of the two negative consecutive cultures (the date sputum specimen collection should be used).

Patients that are culture and smear negative at the commencement of treatment for whatever reason(s) do not get counted in the cohort reporting of culture or smear conversion.

Sputum conversion is slower when using second-line anti-tuberculosis drugs. Culture results showing a few colonies should not be automatically regarded as negative in DR-TB patients, nor should a single positive culture preceded by multiple negative cultures be regarded as treatment failure.

Culture conversion is not equivalent to cure.  A significant proportion of patients may initially convert and later revert to being culture positive, depending on the initial burden of disease and the level of resistance. For these reasons, cultures should be done regularly throughout the duration of treatment.

14.2.3. Other Laboratory Tests

These are liver function tests, serum creatinine, serum potassium, thyroid stimulating hormone. These tests are used mainly to monitor the development and the management of ADRs.

All patients with DR-TB must be offered HIV tests if they do not know their HIV status.

A pregnancy test in females patients of child bearing age is also important on admission and when necessary. Patients spend long periods on treatment after admission; hence it is important to consider pregnancy tests in females who are not on contraception.

14.2.4. Chest X-Rays

Chest x-ray films should be taken whenever the patient’s clinical condition worsens, or whenever surgical intervention is being considered. The chest x-ray film results may remain unchanged or show only slight improvement, this does not mean the patient is not improving on treatment therefore; no changes in treatment should be made on the basis of chest x-ray films alone.

The chest x-ray films must be evaluated using a standardised scoring system at the following intervals:

  • At diagnosis;
  • After completion of the intensive phase of treatment or at six months;
  • Every six months; and
  • At treatment completion.

The chest x-ray film is divided into six zones by the mediastinum and horizontal lines through the 2nd and 4th anterior rib shadows. Each zone is described according to disease and cavitation, as follows:

Scoring System for the Evaluation of Chest X-Rays

 

 
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Disease (a)

 

 

 

Score

 

No disease

 

:

 

Leave blank

 

0

 

< 50% of area affected

 

:

 

< 

 

1

 

≥ 50% of area affected

 

:

 

> 

 

2

 

 

Cavitation (b)

 

 

 

Score

 

No cavitation

 

 

Leave blank

 

0

 

Single cavity, <2 cm diameter

 

:

 

1a

 

0.25

 

Single cavity, 2-4 cm diameter

 

:

 

1b

 

0.50

 

Single cavity, >4 cm diameter

 

:

 

1c

 

1.00

 

Multiple cavities, largest <2 cm diameter

 

:

 

2a

 

0.50

 

Multiple cavities, largest 2-4 cm diameter

 

:

 

2b

 

1.00

 

Multiple cavities, largest >4 cm

 

:

 

2c

 

2.00

 

A composite score is calculated by adding the disease and cavitation scores for each zone, as follows:

 

Zones affected

 

1

 

2

 

3

 

4

 

5

 

6

 

Disease (> / <)

 

 

 

 

 

 

 

Score (a)

 

 

 

 

 

 

 

Cavitation

 

 

 

 

 

 

 

Score (b)

 

 

 

 

 

 

 

Total score (a+b)

 

 

 

 

 

 

The following table presents a summary of parameters to be considered for DR-TB patient monitoring.

 

 

 

 
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14.3. Patient Education and Counseling

 

Education, counselling and emotional support are particularly important, much as in any other chronic life-threatening illness. On-going intensive counselling will also help to ensure good adherence to the treatment regimen and increase the likelihood of a successful outcome.

Patients and their families should also be informed on an on-going basis about MDR- or XDR- TB, its spread, prevention, treatment, potential ADRs, the need for treatment compliance and early testing for MDR- and XDR-TB for other family members should they develop symptoms. Information can be provided by physicians, nurses, community health workers and other health care providers at every encounter with the patient. Information and educational materials should be appropriate to the literacy levels of the population and should also be culturally sensitive.

 

14.4. Treatment Compliance

 

Patients with DR-TB may more likely have had problems with treatment non-compliance in the past. In addition, treatment compliance is made more difficult by prolonged multidrug treatment regimens with drugs that have serious ADRs. Monitoring patient compliance and support measures to facilitate adherence are therefore particularly important.

MDR-TB treatment and, to a lesser extent XDR-TB treatment, can be successful with high overall rates of treatment compliance when adequate support measures are implemented.  Patient support groups and family support for the patients may help improve this.

Since the patients often have only one last chance for cure and there is a serious public health consequence if treatment fails, it is imperative that all patients receive their treatment under strict DOT after discharge from the hospital either in the community or at health facilities. This should be provided in such a way that it does not introduce undue burdens to patients and their families. Long distances and difficulties accessing services may all contribute to treatment interruption.

The first choice for providing community care to DR-TB patients is to use HCWs where possible. When human or financial resources do not permit the use of HCWs, trained community members can serve as effective treatment supporters. However, community members need intensive training, on-going supervision and support by health professionals.

Irregular or noncompliant patients continue to pose a challenge to nurses and community health workers particularly following discharge from hospital, therefore any non-compliance should be addressed as soon as it is detected. The patient must be counselled again and any issues that may be contributing to the non-compliance addressed. If the current arrangement for DOT does not suit the patient the patient anymore, a more suitable arrangement must be agreed upon. The patient must also be assessed for:

  • Any psychiatric symptoms, and referred to a psychologist/psychiatrist for further assessment if necessary.
  • Alcohol and drug abuse and referred for rehabilitation programmes.

Socio-economic factors that could contribute to non-compliance such as lack of money for transport, lack of food which may exacerbate some of the gastro-intestinal effects on taking medication must also be investigated. Where these apply the social worker must be contacted.

When all measures have been taken and the patient is not consistent with taking the medications, a decision should be taken to discontinue treatment.

 

14.5. Maintaining Confidentiality

 

The HCW and community health worker must maintain strict confidentiality at all times to ensure and maintain the patient-provider relationship, as treatment is lengthy. In some cases this may entail arranging a system where the patient receives medication without the knowledge of others.

 

14.6. Social Support

 

The provision of social support to patients may improve chances of adherence to therapy. The social worker must conduct an assessment of the patient’s home environment and ensure that social support is provided for the family members where needed. If the patient was employed, with the patient’s consent arrangements may be made with the employer to provide the necessary leave of absence from work whilst the patient is hospitalised thereby sustaining the monthly income of the patient. Patients who are substance abusers must be started on rehabilitation programmes with intensive counselling as treatment compliance tends to be poor in this group of patients. Organisations such as SANCA can assist with provision of these programmes.

Patients who qualify for social grants or disability grants should be assisted to access these grants. Those who are breadwinners, or who have lost income as a result of admission in hospital and their families are in distress should be assisted to access other benefits – social relief of distress grant, an extension beyond the stipulated six months may need consideration for those patient who need longer hospitalisation (i.e. non-converters/treatment failures).

The social worker should also negotiate with the employers to encourage them to offer the patient “paid” sick leave as far as reasonably possible or lodge an application for access to the

‘unemployment insurance fund’ (UIF) on behalf of the patient whilst hospitalised. An application may be lodged on behalf of the patient who is a breadwinner to access free municipal services through the use of the indigent policy. This is an avenue designed for non-affording people to benefit on basic services like water, electricity and waste removal amongst others. In terms of chapter nine of the Municipal Systems Act, a municipality in relation to the levying of rates and other taxes and the charging of fees for municipal services, it must within make provision for indigent debtors that is consistent with its rates, tariff policies, financial and administrative capacity.

Some of the patients may develop hearing loss due to prolonged use of aminoglycosides or capreomycin resulting in permanent disability and may require disability grants. Applications should therefore be processed as soon as confirmation of deafness is confirmed. 

 

14.7. Management of Treatment Interruption and Default

 

When a patient refuses to continue treatment every effort should be made to convince the patient to continue treatment. This should include explaining the implications of discontinuing treatment, importance of completing the treatment and addressing the reasons for wanting to stop treatment and other patient concerns. In most cases this is due to the side effects and addressing these more aggressively by providing ancillary treatment and rescheduling the doses might help. An evaluation of the patient should be conducted and this must include an assessment of the patient for any psychiatric illness and/or substance abuse and the patient must be referred accordingly when these exist. Where socio-economic factors are contributing to this, they should be addressed. When all these measures fail, and the patient insists on stopping treatment, the patient should sign a refusal of hospital treatment (RHT) form (Annexure 4).

A patient is regarded as having defaulted treatment if s/he has been missed treatment for two consecutive months.  Every effort should be made to recall patients who abscond or interrupt treatment for a day or two, to persuade them to resume treatment. A home visit should be conducted to find out why the patient has defaulted after two days and to ensure that treatment is resumed promptly and effectively. The situation should be addressed in a sympathetic, friendly, and non-judgmental manner. Every effort should be made to address the patients’ concerns or reasons for interruption or abscondment to prevent it from happening again.

In patients where treatment has to be restarted following abscondment, default or interruption, the following should be considered:

  • Commitment of patient to treatment completion;
  • Clinical condition of the patient; and
  • Duration of treatment interruption or default.

A full physical examination must be conducted and sputum specimen obtained for microscopy, culture and DST, a chest x-ray must be done and compared with previous ones for extent of disease. Counselling of the patient must be conducted and patient must sign the patient consent form before treatment initiation.

The treatment will depend on the stage at which the patient interrupted treatment and the clinical condition of the patient on return for treatment. Patients who interrupt treatment for more than six months must be clinically evaluated for active disease and if found to have active disease, must be started on a new treatment regimen based on their resistance pattern. If there is no active TB disease, the decision on treatment must be made by the clinical review committee. If not started on treatment, the patient must be followed up regularly for signs of relapse.

 
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14.8. End of Intensive Phase of Treatment

 

The decision to stop the injectable drug should be made following the review of the clinical picture, smear and culture results, chest x-ray films. The injectable drug can be stopped when:

  • Patient has completed a minimum of six months of intensive phase treatment.
  • Two consecutive negative culture results.
  • At least four drugs to which the strain is still sensitive and are usable.

In patients with high grade resistance, extensive lung disease and in whom the regimen contains only four drugs including the injectable, the injectable may be used for a minimum of 12 months after culture conversion or throughout the treatment period.

 

14.9. If There is No Improvement at Four Months of Treatment

 

If a patient shows minimal or no improvement at the end of the injectable phase, the patient must be re-evaluated as follows:

  • Evaluate treatment compliance.
  • Repeat chest x-ray.
  • Repeat sputum smear microscopy, culture

     - If culture is still positive  repeat first- and/or second-line drug susceptibility testing. Resistance amplification or treatment failure must be considered.

 
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14.10. Recurrence of Positive Cultures after Culture Conversion

 

Re-appearance of single or multiple positive smears or cultures should be considered as possible evidence of treatment failure. Therefore, patients should be re-evaluated to determine the course of action. The DST should be repeated to determine whether this is a different strain from the initial one or there has been resistance amplification. During this period two or more drugs should be added to the regimen whilst awaiting DST results.

If the strain and resistance profile is similar to the initial one, this could be treatment failure in which case the treatment may be modified based on resistance profile, or extended until the patient has had 18 consecutive months of negative cultures.

If the strain and resistance profile is completely different from the initial one, this could be due to contamination or a new infection, the latter being the least likely. The cultures should be repeated twice and documented as negative before concluding that this is due to contamination.

 

14.11. Treatment Completion

 

The patient is considered to have completed treatment when s/he has completed at least 18 months of treatment after culture conversion and 24 months for those who had extensive lung damage at the initiation of treatment. Bacteriological, clinical, and radiological information must be considered when determining the end of treatment for MDR- and XDR-TB.

 

14.12. Follow-up After Treatment Completion

 

Patients who complete a full course of MDR- or XDR-TB treatment should be followed up for at least two years after cure. The follow up visits must be conducted every six months and should mainly focus on:

  • Assessing the patient for symptoms and signs of relapse.
  • Conducting smear and culture every six months.
  • Conducting radiographic evaluation as needed for development of respiratory symptoms.
  • Monitoring response to ancillary medicines in patients who had residual lung disease.

Patients should be advised to report to the nearest clinic when they experience symptoms of TB at any stage. Patients failing to come for appointments must be traced. Therefore knowledge of each patient’s residence during the follow-up phase must be obtained.

 
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14.13. MDR- and XDR-TB Treatment Failures

 

Treatment failures are considered when no response to treatment is seen at six months of treatment (i.e., if bacteriological conversion is not seen or if clinically deterioration is evident). Re-assessment of the regimen and treatment plan, and formulation of a new plan of action are necessary. Avoid adding one or two drugs to an apparently failing regimen, instead redesign the regimen with four effective drugs. Once a patient gets two or more new drugs included in the regimen, with or without omission of certain drugs; this should be considered as a new regimen. The patient will receive an outcome of treatment failure and recorded in a new treatment cohort.

14.13.1. Patients with Suspected MDR-TB Treatment Failure

Patients who show clinical, radiological, or bacteriological evidence of persistent active disease or re-appearance of disease after six months of treatment should be evaluated for possible failure. In addition, patients who show rapid clinical deterioration before month 6 should also be evaluated.

The following steps should be taken for patients with suspected treatment failure:

  • The treatment card should be reviewed to confirm adherence of patient to treatment. The healthcare worker should investigate whether the patient has taken all the medicines. A non-confrontational interview should be undertaken without the presence of the treatment supervisor.
  • A non-confrontational interview with the treatment supervisor should be done in the absence of the patient. Questions should be asked to rule out possible manipulation of the treatment supervisor by the patient. If this is suspected, the treatment supervisor should be switched to another patient and the patient assigned a new treatment supervisor.
  • The treatment regimen should be reviewed in relation to medical history, contacts, and all available treatment reports. If the regimen is deemed inadequate, a new regimen should be designed.
  • The bacteriological data should be reviewed. Often the smear and culture data provides the strongest evidence that a patient is not responding to therapy. A single positive culture in the presence of otherwise good clinical response is not necessarily indicative of treatment failure, especially if follow-up cultures are negative or the number of colonies is decreasing. Positive smears with corresponding negative cultures may reflect dead bacilli, thereby not indicating treatment failure. Repeated negative smear and culture results in a patient with clinical and radiological deterioration may indicate that disease other than DR-TB is also affecting the patient.
  • Other illnesses that may decrease absorption of medication (like chronic diarrhoea) or may result in immune-suppression (like HIV) should be excluded.

14.13.2. Patients with Apparent MDR-TB Treatment Failure

There is no single indicator that determines whether treatment is failing; however, a point is reached when it is clear that the patient is not going to improve. Signs that indicate treatment failure include:

  • Persistent positive smears or cultures after 8 months of treatment;
  • Extensive and bilateral lung disease with no option for surgery;
  • High-grade resistance with no option to add additional agents; and
  • Deteriorating clinical condition that usually includes weight loss and respiratory insufficiency.

All these signs need not be present to declare failure of the treatment regimen; nevertheless, cure is highly unlikely when they all exist. Of note is that the epidemiological definition of treatment failure for recording outcomes is often different from the process of suspending treatment in a patient when it is failing. The epidemiological definition is an outcome to account for the patient in treatment cohort analysis. The clinical decision to suspend treatment is one made after all other options have been explored, and cure of the patient has been determined to be highly unlikely.

 

14.14. Suspending Treatment

 

MDR- or XDR-TB treatment can be terminated provided that appropriate counselling has been offered to the patient, and the patient has been heard before a final decision is made. Termination of treatment should be considered in the following circumstances:

  • Where the patient no longer consents to receiving treatment.
  • Where there is a negligible chance of success, even where the patient wishes the treatment to continue. This would apply to those who are chronic defaulters in whom the treatment may not be effective, may result in amplification of resistance, treatment failure or patients with advanced terminal disease.

Suspension of treatment should only be considered after all other options for treatment have been explored as this is a delicate situation and difficult for family members and caretakers, but it is especially difficult for the patient as treatment is often viewed as his/her only hope. Psychosocial support must be rendered to the patient and family.

If the DR-TB clinical management team is confident that all medications have been taken and that there is no possibility of adding other drugs or surgery, the treatment should be considered a failure and suspension of therapy recommended or provision of palliative care.

The decision to suspend treatment should be made by the provincial DR-TB review committee based on all evidence provided on the patient. The team should recommend a treatment plan. Conditions under which treatment may be suspended include:

  • The patient’s quality of life is poor, particularly when medications used in DR-TB treatment have considerable side effects, and continuing them while the treatment is failing may cause additional suffering.
  • Continuing treatment that is failing can amplify resistance in the patient’s strain, resulting in resistance to all available anti-tuberculosis drugs.  This ‘super-resistant strain’ can be transmitted to others.

A consultative process with the patient and family should take place. Both parties should be made to understand and accept the decision for suspension of treatment and alternative care offered. Depending on the patient’s condition this can be provided at home, hospital or hospice. Usually this process takes a number of visits and occurs over several weeks. Home visits during the process offer an excellent opportunity to talk with family members and the patient in a familiar environment. Treatment should not be suspended before the patient understands and accepts the reasons to do so, and agrees with the supportive care offered. The household should be assessed for risk of infection and family educated on measures to take to minimise transmission risk of infection and patients should be advised to avoid contact with the general public and especially with susceptible persons, such as young children or HIV-infected individuals.

 

14.15. Palliative/Supportive Care

 

A number of palliative measures can be implemented once DR-TB treatment is suspended. Supportive measures are summarised below.

  • Pain control. Paracetamol or codeine with paracetamol gives relief to moderate pain. Codeine also helps control cough; other cough suppressants can be added. If possible, stronger analgesics, including morphine, should be used when indicated.
  • Relief of respiratory insufficiency.  Oxygen can be used to alleviate shortness of breath. Morphine also provides significant relief from respiratory insufficiency and should be offered if available.
  • Nutritional support. Often small and frequent meals are best for a terminally ill person. Intake will decrease as the patient’s condition deteriorates. Treat nausea and vomiting or any other conditions that interfere with nutritional support.
  • Regular medical visits. When treatment is stopped, on-going medical and psychological support to the patient must be provided, through regular visits by the medical team. Depression and anxiety, if present, should be addressed.
  • Continuation of ancillary medicines. All necessary ancillary drugs should be continued as needed.
  • Hospitalisation, hospice care or nursing home care.  Looking after a terminally ill family member at home can be quite difficult. Hospice care should be offered to families who want to keep the patient at home. Inpatient care should be available for those patients where home care is not possible.
  • Preventive measures.  Oral care, prevention of bedsores, bathing and prevention of muscle contractures should be ensured for all patients as part of care. Regular scheduled movement of the bedridden patient is very important.
  • Infection control measures. The patient who is taken off of DR-TB treatment because of failure often remains infectious for long periods of time. Infection control measures should be continued.