Tuberculosis suspect . Any person who presents with symptoms or signs suggestive of TB. The most common symptom of pulmonary TB is a productive cough for more than 2 weeks, which may be accompanied by other respiratory symptoms (shortness of breath, chest pains, haemoptysis) and/or constitutional symptoms .
• Definite case of tuberculosis . A patient with Mycobacterium tuberculosis complex identified from a clinical specimen, either by culture or by a newer method such as molecular line probe assay. In countries that lack the laboratory capacity to routinely identify M. tuberculosis , a pulmonary case with one or more initial sputum smear examinations positive for acid-fast bacilli (AFB) is also considered to be a “definite” case, provided that there is a functional external quality assurance (EQA) system with blind rechecking.
Cure A patient whose sputum smear or culture was positive at the beginning of the treatment but who was smear- or culture-negative in the last month of treatment and on at least one previous occasion.
Treatment completed A patient who completed treatment but who does not have a negative sputum smear or culture result in the last month of treatment and on at least one previous occasion
Treatment failure patient whose sputum smear or culture is positive at 5 months or later during treatment. Also included in this definition are patients found to harbour a multidrug-resistant (MDR) strain at any point of time during the treatment, whether they are smear-negative or -positive.
Co-morbid conditions like malabsorption,HIV+,rapid transit diarrhoe,etc.
Treatment without drug susceptibility and culture
Fact in 2005 ;only 2% of estimated culture proven MDR are treated with 2 nd line drugs
OUTCOME OF XDR TB counted cases in US ,defined on initial DST ,1993-2007 2 1 Lost 2 1 Other 4 2 Removed from meds 9 4 Currently on RX 15 7 Moved 33 15 Died while on therapy 35 16 Completed therapy 46 Alive at DX % N
It is not possible to use more than one injectable (STM, capreomycin or amikacin), because the toxic effect of these drugs is additive: If possible, the aminoglycoside should be given daily for a minimum of three months (and perhaps thrice weekly thereafter).
There is no intermittent regimen validated for use in MDR-TB, but clinical experience is that giving injectable drugs for five days a week (because there is no-one available to give the drug at weekends) does not seem to result in inferior results.
Group 2. All patients should receive a Group 2 injectable agent if susceptibility is documented or suspected. Among aminoglycosides, kanamycin or amikacin is the first choice of an injectable agent, given the high rates of streptomycin resistance in drug-resistant TB Group If an isolate is resistant to both streptomycin and kanamycin ,capreomycin (a polypeptide) should be used.
Group -3 One of the higher generation fluoroquinolones, such as levofloxacin or moxifloxacin, is the fluoroquinolone of choice. Ciprofloxacin is no longer recommended to treat drug-susceptible or drug-resistant TB.
Group 4 . Ethionamide (or protionamide) is often added to the treatment regimen because of its low cost. If cost is not a constraint, p -aminosalicylic acid (PAS) may be added first, given that the enteric-coated formulas are relatively well tolerated and that there is no cross-resistance to other agents.
Group 5. Group 5 drugs are not recommended by WHO for routine use in drug-resistant TB treatment because their contribution to the efficacy of multidrug regimens is unclear. They can be used in cases where it is impossible to design adequate regimens with the medicines from Groups 1–4, such as in patients with XDR-TB.
Some experts recommend using high-dose isoniazid in the presence of resistance to low concentrations of isoniazid (>1% of bacilli resistant to 0.2 μg/ml but susceptible to 1 μg/ml of isoniazid), whereas isoniazid is not recommended for high-dose resistance (>1% of bacilli resistant to 1 μg/ml of isoniazid)
depend on the type of laboratory method used to confirm MDR /XDR
For NTPs using conventional DST methods , there is often a delay of months before results are available to confirm or exclude MDR. While awaiting results, patients who are highly likely to have MDR-TB (such as those whose prior treatment has failed) need an empirical MDR regimen. If MDR is confirmed, this regimen may be continued, or it may be tailored on the basis of susceptibility to drugs other
NTPs using rapid molecular-based DST will be able to confirm MDR-TB within 1–2 days,2 and then can initiate treatment with a standard MDR regimen immediately,or may tailor the regimen later when DST results for second-line drugs become available
Include drugs from Groups 1–5 in a hierarchical order based on potency
Use any of the first-line oral agents ( Group 1) that are likely to be effective.
Use an effective aminoglycoside or polypeptide by injection (Group 2).
In MDR-TB treatment, the intensive phase is defined by the duration of treatment with the injectable agent .
The injectable agent should be continued for a minimum of 6 months , and for at least 4 months after the patient first becomes and remains smear- or culture-negative. ( WHO)
Conversion is defined as two consecutive negative smears and cultures taken 30 days apart.
DURATION OF INJECTABLE : The decision to stop the injectable should depend on the clinical status of the pt.,
the bacteriological data (smears and cultures), the chest X-ray, and the DST results.
In patients infected with highly resistant strains, the clinician may opt to continue the injectable during the entire course of treatment. In these cases, the clinician may decrease the frequency to three times per week
guidelines recommend continuing therapy for a minimum of 18 months after culture conversion. Extension of therapy to 24 months may be indicated in chronic cases with extensive pulmonary damage .
START RX IN 2 ND TRIMESTER OR SOONER IF CONDITION IS SEVERE
MAJORITY OF TERATOGENIC EFFECTS OCCUR IN IST TRIMESTER,THERAPY MAY BE DELAYED UNTIL 2 ND TRIMESTER
AVOID INJECTABLES ,IF UNAVOIDABLE CAPREOMYCIN IS THE AGENT OF CHOICE
AVOID ETHIONAMIDE ,INCREASES NAUSEA AND VOMITING ASSOCIATED WITH PREGNANCY AND TERATOGENIC EFFECTS HAVE BEEN SEEN IN ANIMALS
Special considerations for patients with renal insufficiency
250 mg once daily, or 500 mg/dose three times per week. Yes Cycloserine 400 mg per dose three times per week (not daily) Yes Gatifloxacin 400 mg once daily No change Moxifloxacin 750-1000 mg per dose three times per week (not daily) Yes Levofloxacin 600–800 mg per dose three times per week (not daily) Yes Ofloxacin 25–35 mg/kg per dose three times per week(not daily) Yes Pyrazinamide 15–25 mg/kg per dose three times per week (not daily) Yes Ethambutol Recommended dose &frequency for patients with creatinine clearance < 30 ml/min , or for patients receiving haemodialysis Frequency Drug
12–15 mg/kg per dose two or three times per week (not daily) caution Yes Capreomycin 12–15 mg/kg per dose two or three times per week(not daily) caution Yes Kanamycin 12–15 mg/kg per dose two or three times per week(not daily) caution Yes Streptomycin 4 g/dose, twice daily (PASER ｮ )† No change PAS 250–500 mg per dose daily No change Ethionamide NA - Terizidone Creatinine clearence <30 ml/min or pts receiving hemodialysis Frequency Drug