Summary Antimicrobials Part 4

NURS 5334 Antimicrobials Part 4 Treatment of Mycobacterial Infections • Slow-growing microbes • Requires prolonged treatment • Increased risk of drug toxicity and poor patient adherence • Promotes emergence of drug-resistant mycobacteria Tuberculosis (TB) Global epidemic • Leading cause of death worldwide • New cases in the United States are declining • Cases outside United States are increasing Pathogenesis • Mycobacterium tuberculosis • Transmitted from person to person by inhaling infected sputum that has been aerosolized by coughing/sneezing or by initial infection in the line • Initial infection is in the lungs • Can spread from the lungs to other organs through the lymphatic and circulatory system • In most cases immunity develops within a few weeks and the infection is brought under control • 90% of individuals with primary infection never develop clinical or radiologic evidence of disease (latent infection)may harbor tubercular bacilli for a lifetime unless drugs are given5-10% will have a reactivation after a period of dormancy • Immune system fails to control primary infection = active TB developsNecrosis and cavitation of lung tissueSevere destruction without treatmentLungs become cheese-like in appearanceWithout treatment, tissue destruction progresses and death results • Goals of treatment are to eliminate infection and prevent relapse while preventing the development of drug-resistant organisms Multidrug-resistant TB (MDR TB): Resistant to both isoniazid and rifampin 2 most effect TB drugsinfection with multi-drug resistant organisms greatly increases the risk for death, especially with AIDS Extensively drug-resistant TB (XDR TB): severe form of MDR-TH Resistant to: • Isoniazid (INH) and rifampin • All fluoroquinolones (moxifloxacin) • At least one of the injectable second-line drugs (amikacin, capreomycin) MDR-TB: Acquired in 2 ways: • Through contact with someone who harbors resistant bacteria • Through repeated ineffectual courses of therapyToo short, Dosages too low, Erratic patient adherence, A regimen with too few drugs Prime Directive • Antituberculosis regiments must always contain 2 or more drugs to which the infecting organism is sensitivetreatments are prolongedhigh risk that drug-resistant bacilli will emerge if only one anti-TB agent is employedDrug combinations decrease risk for resistance and incidence of relapse • Some drugs active against actively dividing bacilli, other drugs active against intracellular (quiescent bacilli)chances of killing all bacilli present with proper combination of anti- TB agents are used • Drugs used to treat M. tuberculosis for selective for this organism and do not lead to superinfection Determining Drug Sensitivity • Traditional method: Culture sputum samples in presence of antimycobacterial drugs Slow, takes 6-16 weeks • Initial drug selection is empiric based on • Patterns of drug resistance in the community • The immunocompetence of the patient • Should be adjusted once test results are back • In case of treatment failure, tests need to be repeated Treatment of Active TB: American Thoracic Society, Centers for Disease Control and Prevention and Infectious Diseases Society of America (ATS/CC/IDSA) published clinical practice guidelines for treatment of drug-susceptible TB • Drug selection is based on susceptibility of the infecting organism and immunocompetence of the host, Life-span considerations are also factors • First line drugs • Isoniazid • Rifampin • Pyrazinamide • Ethambutol • Rifapentine and rifabutin are also considered first line • Second line drugs • Cycloserine • Ethionamide • Capreomycin • Para-aminosalicylic acid (PAS) • Aminoglycosides: streptomycin and amikacin • Quinolones: levofloxacin and moxifloxacin • Treatment divided into 2 phases: if infecting organisms are not resistant to isoniazid or rifampintherapy is simple • Intensive phase: Lasts 8 weeks, consists of 4 drugs • Isoniazid, rifampin, pyrazinamide, ethambutol • Continuation: Lasts 18 weeks, consists of 2 drugs • Isoniazid and rifampin (infections that are resistant to a single drug- isoniazid or rifampin-usually respond well) • Isoniazid resistant TB: Treated for 6 months with 3 drugs • Rifampin, ethambutol, pyrazinamide • Rifampin resistant TB: Treated 18-24 months with 3 drugs • Isoniazid, ethambutol, and pyrazinamide • Treatment MDR-TB and XDR-TB: Treatment 24 months minimum, harder to manage • Treatment with 5, 6, or 7 drugs • Isoniazid • Rifampin • Pyrazinamide • Ethambutol • Amikacin • Capreomycin • Levofloxacin • Cyclosereine, • Ethionamide • Or PAS • Last resort infected tissue surgically removedPoor prognosis-40-60% diedetermined by extent of drug resistance, infection severity, and immunocompetence of the host • Patients with TB plus HIV: 2-20% of patients with HIV develop active TB because of their reduced ability to fight infectionrequire longer (several months) and aggressive therapysome have lasted 30 months or more • Interactions with meds for patients with HIV especially RifampinRifampin can accelerate metabolism of most protease inhibitors and most nonnucleoside reverse transcriptase inhibitors (NNRTIs)combining with HIV drugs decreases the effects of HIV drugs • Rifampin is the optimal treatment for TB so optimal treatment will be denied for one of the diseases if HIV pt taking protease inhibitors or NNRTIs cant take Rifampin and vise versa • Rifabutin does not accelerate to the degree of rifampin, so some HIV drugs can be continued with rifabutin • Promoting Adherence: Non-adherence is the most common cause of tx failure, relapse, and resistancepts have to take drugs for long period • Directly observed therapy (DOT): Standard of care in treatment of TB • Each dose is done in presence of observer (usually a rep of health department)DOT and intermittent dosing (2-3X/week)adherence • Evaluating Treatment: Three primary modes: • Bacteriologic evaluation of sputum: Evaluated monthly until 2 consecutive tests are negative • Chest radiographs: Done in patients with negative pretreatment sputum testsRepeated every 2 months after initiating treatment • Clinical evaluation: every clinical visit for Fever, malaise, anorexia, cough must be evaluated at every clinic visit Should be markedly decreases within 2 weeks of initial therapy