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Propranolol

By Q. Berek. The Graduate Center, City University of New York. 2019.

The following statement is better: “Smoking causes harm to the body propranolol 40mg, including high blood pressure 80mg propranolol, cancer 80 mg propranolol, and even death 40mg propranolol. Facial Many facial expressions are pos- A patient says propranolol 80mg, “Sometimes propranolol 40 mg, I take my expressions sible: smiling/frowning 40 mg propranolol, looks of mom’s blood pressure medications astonishment propranolol 80 mg, disappointment , when I have a headache because that’s disapproval , surprise, shock, anger, how I know that my pressure’s up. These Upon hearing this, you may feel expressions may happen involun- surprise, shock, and/or disapproval. Although these feelings may be justi- As a patient is speaking, it may be fied, allowing your facial expression to appropriate to smile, which could show these feelings may discourage mean you are encouraging the the patient from divulging information patient to continue speaking, or it to you because of embarrassment and could indicate that you are amused. In contrast, looking perplexed One may also look perplexed, indi- as you ask the patient why he or she cating that either the patient or you thinks a headache means that his or her need more clarity. Body posture Sitting straight or slumped, relaxed If the pharmacist is sitting slumped in and position or tense, and/or with hands a chair, the patient may perceive that crossed over body may indicate there is a lack of interest on the part one’s desire to be a part of the of the practitioner to be present at the conversation or it may reflect feel- patient visit. In addition, the distance or than just continuing to give informa- space between you and the patient tion to the patient, it may be better to may indicate the balance between pause, and ask the patient a reflective respect for personal space and question such as, “What do you think being close enough to comfort- about starting these new medications? Typically, finding a place to sit where you are close enough to reach the patient but not touching the patient is a good distance. If your therefore you should avoid touching patient is moving around too much the patient in the future. Additionally, or acting restless, it may indicate ner- if your patient appears to be moving vousness or discontent. In addition, around too much, you can ask the touching a patient on the shoulder patient a question such as, “You seem may show empathy or go together to be pacing the room—what is on with making a point; however, some your mind? Eye contact If you keep glancing at your As computerized medical records are computer screen or your phone, it becoming more prevalent, if you are appears to the patient that you are reviewing and documenting informa- not interested in what he or she tion as the patient is speaking, it may is saying; however, maintaining make the patient feel as though you continuous eye contact may make are not actively listening. Addi- visit, you can start by telling your tionally, certain cultures consider patient that you will be documenting eye contact to be a sign of respect in the computerized medical record whereas others think it is more throughout the visit to prepare the respectful to not make direct eye patient. Therefore, you should take the patient is answering your ques- nonverbal cues from your patient tions, you should make eye contact to maintain the right amount of and document this information at a eye contact, understanding that a later time. It has been well documented in the medical field that effec- tive communication with patients leads to better diagnosis and treatment, as well as an improved provider–patient relationship. Although most of this research is related to 5 12 chapter 1 / the patient interview physician–patient communications, it can easily translate to communications between the pharmacist and the patient. This is because pharmaceutical care, like the care pro- vided by a physician, involves (1) curing a patient’s disease, (2) eliminating or reducing a patient’s symptoms, (3) arresting or slowing a disease process, and (4) preventing a disease or symptoms. Even though a pharmacist does not make disease diagnoses like 6 physicians do, a pharmacist must nonetheless evaluate the information obtained from the patient interview, including the possibility of certain diagnoses, to appropriately create an assessment and plan, which may include a referral to the patient’s physician or an emergency room for further evaluation. This is typically documented in the patient’s own words and is therefore quoted in the written or oral presentation. One way to deter- mine the patient’s chief complaint is by asking, “What brings you here today? In the case of no overt complaint, the chief complaint may be goal-oriented, such as “I am here to pick up my refills,” “I am here to discuss my labs,” or “My doctor told me to see you about my sugars. For example, a patient may come in complaining of “being out of his furosemide” and, upon evaluation, it may be determined that the patient is experiencing acute heart failure. This assessment and the subsequent plan will be discussed elsewhere in your documentation. History of Present Illness The history of present illness (hpI) is the story of the illness. The pharmacist will 7 further explore the chief complaint as well as any other potential problems by asking questions about any recent or remote history that may be related to the current illness. Seven attributes need to be addressed to obtain a well- characterized description of the complaint or symptom: location, quality, quantity or severity, timing, setting, factors that aggravate or relieve the symptoms, and associated manifestations. For example, if the patient much worse is it now than it is in pain, characterize the pain by using normally is? If “Would you say that this the symptom is pain, ask the patient to swelling is causing your leg to rate the pain on a scale of 1 to 10. Setting This includes addressing the possible “Have you noticed what cause of the symptom. Do you relieve the or nonpharmacologic therapies used to notice a difference in the symptom relieve the symptoms and their efficacy. Are you experienc- that may be a consequence of the primary ing any shortness of breath or symptom. For example, if a patient complains of a cough, it is not necessary to ask about the “location” of the cough. However, if a patient complains of a headache, specifying the exact “location” of the pain (i. A patient who is telling you parts of his or her story may not realize which parts are pertinent. For example, the patient may not know how and what information needs to be relayed to you so that you can make a complete assessment. It is like a puzzle in that you may know what the completed puzzle will look like; however, you have to pick up each piece; examine its shape and color for hints, such as having a flat side, which indicates that it is a border piece; and then place it near other “like” pieces until you are able to fit all the pieces together. You, as the pharmacist, should start thinking of various questions to ask the patient so that the patient’s responses, or the puzzle pieces, may be put together to ascertain or rule out certain assessments. In the case of the patient interview, you will be assessing each piece of information for its reliability, completeness, and relevance to the problem. You may need to assess a patient’s medical condition during the patient interview even if the patient does not have any complaints regarding that medical condition. If the patient has any of the aforementioned symptoms, they would be termed pertinent positives, or the presence of symptoms that are related to the medical the patient interview 15 condition that is being assessed. In contrast, if these symptoms are absent, they would be termed pertinent negatives, or the absence of symptoms related to the medical condition being assessed. Asking these focused questions about pertinent positive and negative symptoms contributes to the assessment of heart failure in this patient. Another way to use the technique of asking about pertinent positives and nega- tives is to rule out or rule in possible diagnoses. For example, to determine a possible cause for the polyuria (increased urination) a patient is experiencing, you will need to ask focused questions. Additionally, pertinent positives or negatives are not limited to symptoms but may include other information obtained from the family history or past medical history. In order to accurately make a diagnosis, in collaboration with a medical professional, these findings from the patient interview would need to be coupled with diagnostic tests, including blood work and/or urine analysis. The purpose of this example is to illustrate the use of questions to discover either the presence or absence of pertinent findings that assist in painting an accurate and complete picture of the patient’s story. Past History The past history includes the past medical history, surgical history, history of child- hood illnesses, and obstetric/gynecologic history. Aspects of health maintenance, such as immunizations and screening tests, should be included as well. Each of the components of the past history should include the information discussed below. As pharmacists, we do not usually obtain a complete past history from a patient; rather, we rely on the informa- tion documented by a medical student, resident, or physician. However, sometimes it is appropriate to ask the patient about parts of his or her past history and/or to use any information gathered previously to determine the appropriate care for the patient. Therefore, it is vital to know the components of the past history and the questions that need to be asked. To ensure completeness, you may need to ask the question in various ways and, at times, gently probe. For example, if you notice that the patient is not sure what you mean by “medical conditions,” you might ask, “Do you have any medical conditions, such as diabetes or high blood pressure? You could ask the patient, “What childhood illnesses, such as measles or chickenpox, did you have as a child? The gyneco- logic history includes onset of menstruation, date of last period, use and type of birth control, and sexual function. Although the pharmacist does not typically gather this history, some of this information may be pertinent to patient care provided by the pharmacist. For example, knowledge of an infant’s birth weight can help you deter- mine whether the mother has a risk factor for diabetes, which, in turn, may influence whether you would recommend diabetes screening for the patient. One way to gather this information would be to ask directly, for example, “There are many risk factors for diabetes, including the birth weight of your children. In this situation, you might ask the patient questions such as, “When did the unprotected sex happen? Health Maintenance/Immunizations This part of the medical history includes information on what immunizations the patient has received, such as influenza, pneumococcal, tetanus, and hepatitis B, as well as the dates they were obtained. Based on this information, you can then recommend any new or booster immunizations the patient may need. The dates and results of screening tests, such as mammograms, Pap smears, and tuberculin tests, should also be included. Information on diabetes and cholesterol screenings may also be included in this section, even though these tests are part of the objective data. These screen- ing tests typically occur because of recommendations from guidelines and are meant to allow for preventative treatments and early diagnosis; therefore, asking the patient about this during the past history component of the patient interview enables you to make recommendations based on the information you have gathered. Family History The family history (Fh) is health information about the patient’s immediate rela- tives. These relatives include parents, grandparents, siblings, children, and grandchil- dren. Because many medical conditions have a genetic component, the purpose of the family history is to determine potential risks factors for the patient’s current and future health. Typically, relatives such as cousins, aunts, and uncles are not included in the family history; however, for certain medical conditions that carry a high genetic link questions about the patient’s family history may be appropriate. In addition, if the person is 18 chapter 1 / the patient interview deceased, ascertain the age at death and the cause of death. It is important to include 4 this specific information because it may determine certain risk factors a patient may carry. For example, if a patient’s father died at the age of 45 secondary to a myocardial infarction, the patient then has a risk factor for coronary artery disease. One way to deter- mine the patient’s family history is to ask, “Are your parents and grandparents alive? The basic social history consists of asking the patient about past and present use of tobacco, alcohol, and illicit substances. If these are currently consumed, you should inquire as to how much and how often each is utilized. In addition, if a patient is a former user of any of these substances, it is vital to ask the patient at subsequent visits if he or she remains abstinent or if relapse has occurred. Because many of the these questions can be very personal and some patients may be reluctant to share such information, either out of embarrassment or fear of being judged, you should ask these questions with sensitivity and respect. However, it is important to be direct so that patients realize these questions are important with regard to their care. For both former and current tobacco users, you should ask at what age they started (and quit); what form of tobacco they use or used, including cigarettes, chewing tobacco, and/or cigars; and quantify the amount. For cigarettes smokers, you should ask how many cigarettes or packs they smoke (or smoked) per day. It is necessary to ask specific questions, because although one drink is tech- nically considered to be 12 ounces of beer, 5 ounces of wine, or 1. It will help if you are straightforward and nonjudgmental when asking about illicit substance use. One way to ask this question is, “Do you currently take, or have you taken in the past, any illicit drugs? It includes the presence of any symptom, even one that the patient may not have deemed to be significant or may have forgotten because of his or her focus on the chief complaint. Additionally, pharmacists may also be part of a medical team, and therefore should be aware of all of the components of a patient interview even if they are not the ones ask- ing the questions. Prior to starting this part of the interview, let the patient know that you will be asking several questions to assess any potential symptoms he or she may be experiencing. Oftentimes, some of these systems may be addressed concurrently with another part of the interview. For example, after checking the patient’s blood pressure, you may ask if the patient has had any dizziness or palpitations. They are taught to develop their own systematic approach to ensure a thorough and accurate physical exam. The comprehensive physical exam includes measurement of vital signs such as height, weight, temperature, blood pressure, and pulse, as well as the observation, inspection, and palpation of the patient’s body from head to toe. Although physicians often complete this part of the patient assessment, pharmacists are also skilled at completing parts of the physical exam. These parts include, but are not lim- ited to, measuring vital signs and inspecting and palpating parts of the body related to the patient’s complaint. For example, a pharmacist may assess the severity of lower leg edema by inspecting and palpating the area of swelling. Additionally, pharmacists may conduct mental status examinations or assess the effects of a stroke by examining the patient for facial droop, arm drift or strength, and speech abnormalities. The medication history provides insight into the patient’s current and past medications, adverse drug reactions or allergies, adherence, the patient’s own understanding about his or her medications, and any other concerns a patient may have regarding his or her medications. Asking 9 pertinent questions with a systematic approach, utilizing appropriate technique, and actively listening to the patient will enable you to collect a thorough and accurate medication history. This, in turn, will enable you to identify, prevent, and/or resolve any active or potential drug-related problems. For example, a patient who is taking warfarin may also tell you she is taking ibu- profen 200 mg twice daily for arthritis pain. This information provides you with an opportunity to assess the patient’s arthritis pain and inquire about what other agents have been tried to treat the pain.

In children propranolol 40mg, repeated vomiting sometimes results from high fever and can be reduced by tepid sponging and administration of paracetamol 40 mg propranolol. In adults (not in children) aspirin may be given as an alternative to paracetamol propranolol 80mg. The patient should also return for medical attention if fever has not resolved by the last day of treatment propranolol 40 mg. Co-blister packs of separate scored tablets containing 50 mg of Artesunate and 153 mg base of amodiaquine respectively 80 mg propranolol, are also available 80mg propranolol. Therapeutic dose: A dose of 4 mg/kg/dayArtesunate and 10 mg/kg/day amodiaquine is given once or twice a day for 3 days 40mg propranolol, with a therapeutic dose range between 2–10 mg/kg/day Artesunate and 7 propranolol 80 mg. Artesunate-Amodiaquine Co-Blistered Formulation: In the co-blistered formulation , tablets of each drug come packaged together . They may be administered either as a single dose each day (refer to Table 1) or as daily divided doses (Table 2). The product is available in four presentations for four age ranges (2-11 months, 1-6 years, 7-13 years and 14 years and above) and each presentation is easily identified with a specific color code and pictograms to ensure appropriate usage. The product packaging clearly indicates which dosing strength applies to which age group. Use of the fixed dose combination product improves adherence and ease of administration. Therapeutic dose: The recommended treatment is a 6-dose regimen over a 3-day period. The dosing is based on the number of tablets per dose according to pre-defined weight bands (5–14 kg=1 tablet; 15–24 kg=2 tablets; 25–34 kg = 3 tablets; and > 34 kg= 4 tablets) for 3 days. Lumefantrine absorption is enhanced by co-administration with fat containing meal. A flavoured dispersible tablet paediatric formulation of Artemether plus Lumefantrine is now available, enhancing its use in young children. Note: Arthemether- Lumefantrine is not recommended for infants under 5 kg or under 6 months of age. Therapeutic dose: A dose of 4 mg/kg/day dihydroartemisinin and 18 mg/kg/day piperaquine once a day for 3 days, with a therapeutic dose range between 2–10 mg/kg/day dihydroartemisinin and 16–26 mg/kg/day piperaquine. Paracetamol in tablet, syrup or suppository forms may be given every 4-6 hours until the temperature is normal. For children above 14 years and for adults, Aspirin (acetyl salicylic acid) may be given instead of Paracetamol. Patients who have been diagnosed with malaria and treated may fail to improve for various reasons including: Ÿ The presenting symptoms, such as fever, were due to a cause other than malaria. Absence of other differential diagnosis of common febrile illness such as upper respiratory tract infections and urinary tract infection. Inadequate treatment can be defined as failure to complete the initial course of treatment for whatever reason (e. One or more of the following criteria listed below is an indication for referral of a malaria patient to a hospital: Ÿ Altered consciousness (confusion, change in behaviour, delirium, coma persisting for over 30 minutes after convulsion). If the patient is already being managed in a hospital, the presence or persistence of the above conditions may prompt referral to a higher level of care. If referral is not possible immediately, continue treatment until referral is possible. Have the patient lie down on his/her side during the journey to avoid aspiration in case of vomiting. Send a clear letter or referral form about the clinical picture, the type of treatment given, dosages, times and route of administration for any medications given. Due to the risk of adverse drug effects in the first trimester of pregnancy, it is especially preferable to confirm the presence of malaria parasites before treatment is initiated. However, unavailability of laboratory testing should not be a reason for withholding anti-malaria treatment in pregnant women. Other conditions including urinary tract infection; pneumonia; enteric fever; intra- uterine infections (chorioamnionitis) may present with fever during pregnancy. To rule out other non-malarious causes of fever, it is therefore essential to take a comprehensive history and conduct a thorough examination, followed by a request for other relevant laboratory investigations (such as urine analysis). Two options are available: Ÿ Oral Quinine at 10mg/kg body weight (max 600 mg) three times per day for seven days. However, their use shall not be withheld in cases where they are considered to be life saving, or where other anti-malarials are considered to be unsuitable, including the possibility of non-compliance with a 7 day treatment with quinine. The following should be established before a diagnosis of treatment failure is made: a. That she completed the full treatment course and did not vomit after taking medications. That the symptoms are not due to other common infections such as ear, nose, throat, urinary tract infection, chorioamnionitis, enteric fever (typhoid), etc. In the event of treatment failure, the alternative drug to be used depends on which medicine was given first. It mostly occurs in children under five (5) years of age, pregnant women and non- immune individuals. The most common complications of severe/complicated malaria responsible for most deaths particularly in children under 5 years of age are: Ÿ Cerebral malaria – Prolonged coma not attributed to any other cause in a patient with falciparum malaria. The patient is likely to have experienced some of the typical symptoms of malaria. These may have included: chills, rigors, headache, body aches, sweating, nausea/vomiting, loss of appetite, and/or abdominal pain. In all patients, clinical diagnosis of severe/complicated malaria should be made in a patient with: Ÿ fever (history of fever or axillary temperature³ 38. In young children, a clinical diagnosis of severe/complicated malaria can also be made if there is; Ÿ fever (history of fever or axillary temperature ³ 38. While laboratory tests should not delay the initiation of treatment, it is mandatory to test for Plasmodium falciparum. Note: High parasitaemia is not always present in severe disease, and the initial blood slide examination may be negative. Where there is high clinical suspicion of malaria, the test should be repeated at 6 hourly intervals. Laboratory Findings: Ÿ Severe normocytic anaemia (severe anaemia; haematocrit <15% or Hb <5g/dl). These are non-specific clinical findings that suggest the presence of serious underlying illness. A child with fever and any general danger sign should be diagnosed and treated for severe/complicated malaria. The goals of management of severe/complicated malaria are to provide: Ÿ Urgent treatment of life threatening problems. This section provides guidance on management of severe/complicated malaria in the outpatient setting, prior to referral. If referral is not feasible immediately, continue treatment until the referral becomes possible. It is especially appropriate for the home/community setting, where there are no trained health workers who can administer injections. In the event that an artesunate suppository is expelled from the rectum within 30 minutes of insertion, a second suppository should be used especially in young children. The buttocks should be held together for 10 min to ensure retention of the rectal dose of artesunate. Table 9: Rectal Artesunate (Pre-Referral Treatment in Children) Weight (kg) Age Artesunate Dose Regimen (mg) 5 – 8 0 – 12 months 50 One 50mg suppository 9 – 19 13 – 42 months 100 Two 50mg suppositories 20 – 29 43 – 60 months 200 One 200mg suppository 30 – 39 6 – 13 years 300 Two suppositories of the 50mg and one of the 200mg suppository >40 > 14 years 400 Two of the 200mg suppositories Table 10: Rectal Artesunate (Pre-Referral Treatment in Adults) Weight (kg) Artesunate Dose (mg) Regimen 40 – 50 400 Two of the 200mg suppositories 60 – 80 800 Four of the 200mg suppositories >80 1200 Six of the 200mg suppositories 4. In situations where the patient is still within the facility following referral, parenteral treatment should be continued while waiting until patient leaves. Shake for 2-3 minutes minutes to ensure minutes to ensure to ensure dissolution dissolution into a dissolution into into a clear solution. Step 4 Step 4 Step 4 4 Withdraw the 4 Withdraw the 4 Withdraw the required amount of required amount of required amount of solution and inject at solution and inject solution and inject the chosen site. To prepare this, draw 2mls of Quinine 600mg and add 4mls of sterile water or saline (not dextrose). Supportive Treatment for Severe/Complicated Malaria in the Outpatient Setting Use ofAntipyretics In young children, high temperatures are associated with vomiting, often regurgitating their medication, and seizures. Antipyretics should be used if axillary temperatures are ³ 38°C) and the patient can tolerate oral medication. Paracetamol (acetaminophen) 15 mg/kg every 4 hours is widely used; it is safe and well tolerated, given orally or as a suppository (Refer Tables 6 and 7 for dosing). In case of convulsions the following should be done: Ÿ Clear and maintain airway Ÿ Treat with diazepam: – A slow intravenous injection of diazepam [0. Nursing Care Ÿ Provide good nursing care: For example, keep an unconscious patient on his or her side and monitor vital signs. If Hb<5gm/dl and Hct<15 - 20%, do grouping and cross-matching for possible transfusion. Parenteral treatment provides adequate blood-serum concentrations as quickly as possible initially. Parenteral treatment should continue until patient is well enough to swallow, and for at least 24 hours even if the patient is well enough to swallow before 24hours. Reconstituting ParenteralArtesunate Artesunate is dispensed as a powder of artesunic acid in vials of 30mg, 60mg or 120mg and usually in packs containing sodium bicarbonate solution and normal saline. Check the brand available at your facility and follow the general instructions provided below. Step 2 Step 2 Step 2 Gently Shake for 2–3 Gently Shake for 2–3 Gently Shake for 2–3 minutes to ensure minutes to ensure minutes to ensure dissolution dissolution dissolution into a clear solution. Withdraw the required amount required amount required amount of the solution of the solution and of the solution and and inject slowly inject slowly at a inject slowly at a rate at a rate of 3-4ml rate of 3-4ml per of 3-4ml per minute. It should always be given by slow rate-controlled infusion, never by bolus intravenous injection. The dose is Quinine Hydrochloride salt at 10mg per kg body weight (maximum dose 600mg) 8 hourly in 5-10ml/kg of dextrose saline or in 5% dextrose over 4-8 hours. Use the appropriate Quinine dilution for adults or children, as described above in Section 4. Cinchonism is mild when Quinine is used in the recommended doses and subsides spontaneously when administration of the drug ends. The most serious frequent nd adverse drug reaction for injectable Quinine is hypoglycaemia, particularly in the 2 rd and 3 trimesters of pregnancy. In most other respects, however, the treatment of severe/complicated malaria in pregnancy shall be the same as the treatment of severe/complicated malaria for the general population. Supportive care may include the following: Ÿ Blood Transfusion for severe anaemia. Exclude other treatable causes of coma (such as hyperglycaemia, and bacterial meningitis). If injectable glucose is not available, give glucose solutions through nasogastric tube (glucose powder or sugar water). If the child is not able to breastfeed but is able to swallow: Give expressed breast milk, or if not available, consider giving sugar water. If the child is not able to swallow, give 50ml of expressed breast milk or sugar solution must be given by nasogastric tube. Note: The routine administration of bolus fluid infusion for resuscitation is contraindicated. For life- threatening hypoxaemia, consider intubation with mechanical ventilation. Severe Anaemia: Diagnosed in patients with Hb <5g/dl, or packed cell volume <15%; and/or in anaemic patient with signs of heart failure (dyspnoea, enlarged liver, gallop rhythm). Transfuse with 10ml per kg body weight packed cells or 20ml per kg of whole blood as appropriate. Acute Renal Failure: Exclude dehydration, maintain strict fluid balance, monitor fluid input and urine output (urine output: 25-30ml/hour). Avoid drugs that increase the risk of gastro-intestinal bleeding: Ÿ Corticosteroids. Vital Signs: blood pressure, body temperature, pulse, respiratory rate four (4) hourly. While patient is hospitalised, it is recommended to repeat at least six (6) hourly. Check for neurological sequelae (deficit): Assess patient for possible neurological sequelae (deficit) of the disease or the treatment. This is important in children, since it is likely that 10% of them may develop neurological sequelae after they recover from cerebral malaria. Perform follow-up laboratory tests on the 7 and 14 days: Ÿ Thick and thin blood films Ÿ Haematocrit Ÿ Haemoglobin c) ForAdults and Children Recovering from SevereAnaemia: Ÿ Give iron and folic acid for two months with regular follow-up Ÿ If child has sickle cell disease, give folic acid only, unless laboratory findings indicate the need for iron supplementation. It is delivered through trained community members living as close as possible to where the children under-five years live. Home Management of malaria allows for coverage of the health services for malaria to extend beyond the reach of health facilities. Supportive care should also be provided, including tepid sponging and administration of paracetamol. The following treatment guidelines apply: Ÿ For dosing regimens of Artesunate-Amodiaquine and Paracetamol, refer to Sections 3. The following categories of patients should not be managed at home, but referred urgently to the nearest community health officer or health center for further evaluation and treatment.

80mg propranolol

For extensive disease propranolol 80 mg, day) propranolol 40mg, ethambutol (15 mg/kg/d) propranolol 80mg, and consideration of inclusion at least 2 months of intermittent (twice or three times weekly) of either amikacin or streptomycin for the first 2 or 3 months streptomycin or amikacin is recommended 40 mg propranolol, although longer par- of therapy (see below) 80mg propranolol. Selected patients in this disease category enteral aminoglycoside therapy may be desirable in patients with might be considered for surgery as well 40mg propranolol. Patients receiving very extensive disease or for those who do not tolerate other clarithromycin and rifabutin should be carefully monitored for agents propranolol 40 mg. Baseline audiometry testing 80 mg propranolol, together with repeat medication regimen at 1–2 weekly intervals) , to evaluate toler- interval testing while receiving parenteral aminoglycoside ther- ance to each medication and medication dose . Some experts prefer amikacin to lar/bronchiectatic patient on all drugs at once on full doses of streptomycin due to a perceived difference in the severity of each medicine frequently results in adverse drug reactions re- vestibular toxicity between the two drugs. Expert consultation should be sought for patients who within 12 months on macrolide-containing regimens (266). The optimal drug regimen for treating macrolide-resistant strains is a major Context: issue to be addressed in future studies as resistant strains become The following recommendations are for patients with macrolide- more prevalent. A number of other drugs have been used in clarithromycin 500–1,000 mg/day or azithromycin 250 mg/ multidrug regimens in the past, but they are limited by little or no day, ethambutol 15 mg/kg/day, and rifampin 10 mg/kg/day evidence of clinical efficacy and toxicity (e. The preliminary review of data from diarrhea) and reversible hearing impairment (285). Simi- more than double rifabutin serum levels, likely by inhibiting larly, the role of inhaled antibiotics, such as tobramycin and ami- hepatic metabolism of rifabutin. Multiple factors can interfere with the occur with a decrease in rifabutin dosage. The timing of the positive munologic reactions (acute renal failure, thrombocytopenia). Most experts feel that toxicity with rifampin is much less fre- Patients whose sputum cultures become negative on therapy quently encountered than with rifabutin. Patients who complete 10 to 12 months receiving multiple other medications whose efficacy may be com- of negative cultures on therapy, however, but then have either promised by rifampin coadministration. Clarithromycin enhances rifabutin gic reactions, especially in elderly patients with nodular/bronchi- toxicity (especially uveitis), whereas the rifamycins, rifampin ectatic disease whose weight is often in the 45- to 55-kg range more than rifabutin, lower clarithromycin serum drug levels (Table 6). Patients whose dis- with low creatinine clearances or low body weight require even ease is predominantly localized to one lung and who can tolerate lower doses (i. There are, however, significant limitations to the wide patients treated medically (263, 264). Presumably, patients would need lung resectional surgery for mycobacterial disease is potentially to meet preoperative criteria similar to those for patients under- associated with significant morbidity and mortality (301, 302). Second, these studies are re- Several single-center, retrospective studies including small ported from centers with experience in the surgical management numbers of patients suggest that surgery can be associated with of mycobacterial diseases. Even in experienced hands, this type American Thoracic Society Documents 393 of surgery is associated with a relatively high morbidity. Third, with bronchiectasis include autogenic drainage, oscillating posi- these data likely represent very highly selected patient popula- tive expiratory pressure devices, and high-frequency chest com- tions, and the results from these reports may not reflect the pression devices. These modalities offer additional mucus clear- likely more variable clinical and microbiologic results expected ance advantages to patients, and should be considered in in patients with complex, advanced disease. A special circum- individuals with significant mucus production and clearance stance that merits discussion is the surgical removal of a solitary problems. Other potentially important considerations include nu- directly assessing this problem, expert consensus is that, in the trition and weight gain, and exercise and cardiovascular fitness. There are few centers with extensive experience with my- female predominance, and nearly all reported cases are in whites cobacterial surgery. For children with recurrent disease, a second surgical pro- Considerations in delaying or withholding treatment. An alternative for recurrent disease tinction between colonization and invasive disease is not rele- or for children in whom surgical risk is high (e. Consideration should excisional surgery (or surgical debridement) and chemotherapy also be given to the use of adjunctive therapies, in addition to is usually performed. Clearly, these measures may be estimated 37,000 cases in the United States in 1994 (17). Rifabutin cannot be used with certain of these drugs and underlying immunosuppression. Routine monitoring is not indicated unless the tise or consultation with experts in this field. Although monotherapy with T-cell count of over 100 cells/ l for at least 12 months (312). Ethambutol is considered as the second drug to be used, with Most of the reports of treatment of M. O nthebasis a dose of 450 mg/day did appear to offer modest clinical benefit of both efficacy and ease of use, azithromycin—given as 1,200 mg when used as a third drug (313). For patients with macrolide-resistant strains, treatment regimens are far less Treatment successful. Drugs that should be considered for inclusion are Clarithromycin 500 mg orally twice daily Azithromycin 500 mg daily aminoglycosides, such as amikacin, and a quinolone, such as Ethambutol 15 mg/kg orally daily Ethambutol 15 mg/kg daily moxifloxicin. Combinations of clarithromycin and rifabutin may result Rifabutin†300 mg orallydaily in high serum levels of rifabutin and have been associated with * For evidence quality, see Table 1. American Thoracic Society Documents 395 once weekly—is the preferred agent (Table 6) (320). Therefore, routine screening of respiratory or gastroin- (341, 344, 345, 347–350). Four-month sputum con- with the same phage type as those isolated from patients have version rates with rifampin-containing regimens were 100% in been recovered from drinking-water distribution systems in the 180 patients from three studies (344, 345, 347). Two patients Netherlands and environmental isolates of the same genotype failed therapy after initial sputum conversion and both failures as clinical isolates have been identified in France (325, 327). Long-term relapse rates with rifampin-containing regi- subspecies or types are present among both environmental and mens were very low, with only one relapse recorded among human isolates (328–333). Because of the excellent outcomes with type responsible for human infection (328–336). A second group of 14 patients were treated with is the second most common nontuberculous mycobacterium that the same regimen but for a total of 18 months. The treatment regimen for disseminated disease no disease relapses after 46 months of follow-up (95). There is successfully with a regimen that consists of high-dose daily isoni- no recommended prophylaxis or suppressive regimen for dissem- azid (900 mg), pyridoxine (50 mg daily), high-dose ethambutol inated M. The southeastern United States from Florida to cin or amikacin for a total of 6 months (342). The excellent in vitro activity accidental trauma or surgery in a variety of clinical settings (173). However, several studies of post- mycin or azithromycin), moxifloxacin, and at least one other injection abscesses in which no therapy was given revealed dis- agent based on in vitro susceptibilities, such as ethambutol or ease that persisted in most patients for 8 to 12 months before sulfamethoxazole, are likely to be effective for treatment of a spontaneously resolving. The largest group of patients with this lung disease are white, female nonsmokers, and older than 60 years, with no 1. Patients should receive a daily regimen including rifampin predisposing conditions or previously recognized lung disease. The distinguishing feature of patients with three-drug regimen is recommended based on in vitro suscep- a recognized underlying lung disease is that their M. Removal of foreign 50 years, and almost all patients younger than 40 years have one bodies, such as breast implants or percutaneous catheters, is of the predisposing disorders (32). Approximately 15% of patients with culture positivity, short of conversion to negative culture, are M. The natural history of this disease depends outlined above) with amikacin plus cefoxitin or imipenem for 2 primarily on the presence or absence of underlying disorders. For some patients, symptoms can be a study published in 1993, death occurred as a consequence of controlled with intermittent periods of therapy with clarithro- M. Because of vari- can be realistically administered to control the symptoms and able in vitro drug susceptibilities to some drugs, antibiotic suscep- progression of M. Because side effects tibility testing of all clinically significant isolates is recommended. For patients with underlying esophageal or other swallowing For serious skin, soft tissue, and bone infections caused by disorders, treatment of the underlying condition can result in M. The macrolides are the only oral include three newer classes of drugs, the oxazolidinones, the agents reliably active in vitro against M. The lower dose (10 mg/kg) should been treated with linezolid and a companion drug, usually a be used in patients older than 50 years and/or in patients in macrolide, with mixed results. The three- usually recommended antibacterial doses (600 mg twice daily) times-weekly amikacin dosing at 25 mg/kg is also reasonable, is often associated with severe side effects, such as anemia, pe- but may be difficult to tolerate over periods longer than 3 months ripheral neuropathy, nausea, and vomiting. The amikacin combined with high-dose cefoxitin (up to 12 g/d given intravenously in divided doses) is recommended mg/day, is associated with fewer gastrointestinal and hematologic for initial therapy (minimum, 2 wk) until clinical improvement side effects and may still have significant antimycobacterial activ- is evident. The tetracycline derivatives, glycylcyclines, especially choice of an alternative agent such as imipenem (500 mg two tigecycline, also have in vitro activity against M. This to four times daily), which is a reasonable alternative to cefoxitin drug must be given intravenously and it is known to cause nausea (175, 359, 360). For serious disease, a minimum of 4 months of and anorexia in some patients when given long term for myco- therapy is necessary to provide a high likelihood of cure. Telithromycin, a ketolide, in limited testing bone infections, 6 months of therapy is recommended (354). At present, there is no reliable or dependable antibiotic The optimal therapy for M. Recently, additional species, including cefoxitin, or imipenem) or a combination of parenteral M. Skin, bone, and soft tissue disease are the most important clinical manifestations of M. Isolates are susceptible to amikacin (100%), (l00%), linezolid (90%), imipenem (60%), amikacin (50%), clo- ciprofloxacin and ofloxacin (100%), sulfonamides (100%), cefox- fazimine, doxycycline (25%), and ciprofloxacin (20%). Recent studies have shown that all isolates penem is preferred to cefoxitin because M. Of patients (all adults) treated with mono- for clarithromycin, macrolides should be used with caution. Drug therapy at 500 mg twice a day for 6 months, all were cured susceptibilities for this species are important for guiding effective except for one patient (8%) who relapsed with an isolate that therapy. The optimal minimize the risk of macrolide resistance) is necessary to provide choice of agents is unknown, and would likely be dictated by a high likelihood of cure. For bone infections, 6 months of ther- patient tolerance; however, any two-drug combination based on apy is recommended (354). Removal of foreign bodies, such as breast implants a minimum of 4 months of therapy with at least two agents with and percutaneous catheters, is important, or even essential, to in vitro activity against the clinical isolate is necessary to provide recovery. For bone infections, 6 months of ther- For corneal infections, first-line treatment often involves topi- apy is recommended (173). Amikacin, fluoroquinolones, clarithromycin, extensive disease, abscess formation, or where drug therapy is and azithromycin are usually drugs of choice, depending on the difficult. Removal of foreign bodies, such as breast implants and in vitro susceptibility of the organism recovered from the infected percutaneous catheters, is important, and probably essential to tissue. Because of the unusual culture require- have been recovered from cultures of blood, bone marrow, liver, ments of M. Available data sug- tients (especially organ transplant recipients), such as skin lesions gest that most isolates are susceptible to amikacin, rifamycins, or ulcerations, lymph node aspiration, joint fluid, or other undi- fluoroquinolones, streptomycin, and macrolides (162, 366). Last, specimens obtained from Optimal therapy is not determined, but multidrug therapies adenitis in immunocompetent children should be cultured for including clarithromycin appear to be more effective than those M. Agents that appear to be active environment and in clinical laboratories but is almost always in vitro include amikacin, clarithromycin, ciprofloxacin, rifampin, considered nonpathogenic. It is readily recovered from shown variable susceptibility but all isolates are resistant to eth- freshwater, pipelines, and laboratory faucets (88, 203). In a recent study, only 23 confirmed mens including clarithromycin, rifampin, rifabutin, and ci- clinically significant cases were found before 1992, and these profloxacin (64, 160, 391, 392). Surgical excision alone is usually cases antedated accurate molecular identification. However, oc- adequate treatment for lymphadenitis in immunocompetent casionally, M. It is also problematic in the laboratory, causing are necessary for confirmation of identification. These associated with multiple pseudo-outbreaks resulting from con- outbreaks have implicated contaminated tap water or ice, topical taminated automated bronchoscope-cleaning machines and have anesthetics, and a commercial antibiotic solution used to sup- been recovered from metalworking fluids (143, 206, 395, 396). It has lesions, corneal ulcers, joint fluid, central venous catheter sites, been hypothesized that M. Pulmonary disease with this organism has also ingested by patients before expectoration, tracheal suctioning, been reported (396). Thus, it may be advantageous to avoid rinsing or kacin and clarithromycin but resistant to ciprofloxacin, doxycy- drinking tap water or other beverages made from tap water for cline, cefoxitin, tobramycin, and sulfamethoxazole (143). The optimal therapy for this organism is unknown; however, Similar suggestions have been made to avoid contamination with successful therapy is likely difficult due to the extensive antibiotic other tap-water species, such as M. In a study from France, 63 patients in the United States, with most isolates recovered from Florida, were treated for an average of 3. Treatment failure was related to deep struc- synovitis and cutaneous infections, also has been reported (197, ture involvement but not to any antibiotic regimen. Susceptibility testing is not vitro antimicrobial susceptibilities among strains, which may be routinely recommended and should be reserved for cases of at least partially explained by differences in susceptibility tech- treatment failure. In one study that included 54 respiratory fish tanks or nonchlorinated swimming pools (407).

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