Antimicrobial Use in Clinical Practice

Transcription

1 Antimicrobial Use in Clinical Practice Dr. Andrew M. Morris Mt. Sinai Hospital/University Health Network Department of Medicine

2 Introductory tips don t learn too many individual antibiotics no doctor should know more than about a dozen antibiotics try to understand principles rather than specifics, and don t bother learning dosages Dr. Vellend covered many of the basic principles surrounding antimicrobial use... any repetition is deliberate (to aid in recollection)

3 An example of an antimicrobial repertoire amoxicillin/ ampicillin cloxacillin piperacillintazobactam cephalexin/ cefazolin cefotaxime or ceftriaxone azithromycin or clarithromycin clindamycin metronidazole ciprofloxacin levofloxacin or moxifloxacin trimethoprim-sulfamethoxazole gentamicin vancomycin

4 Antimicrobial rules to live by treat the patient, not the lab report don t take credit for curing a self-limited disease with antibiotics don t use broad-spectrum, risky, expensive or new antibiotics for treating mild/minor infections don t treat a fever with antibiotics don t stick with a losing combination i.v. antibiotics should be avoided the best antibiotics are made of steel when the stakes are high, don t be a minimalist

5 Case 1 45 yo woman, previously well works as a pharmaceutical rep; triathlete allergic to penicillin (hives) because of genetic screening, had bilateral prophylactic mastectomies (with plan for tissue expander breast implants) post-operatively, wound healed well: a drain was left in situ (for a seroma), and the clinic nurse sent the fluid for Gram stain and culture prior to removing the drain

6 Case 1

7 Case 1 Date: (14:09) Patient: Merrick, Linda H. ( ) Requesting MD: Singh, P.J. Specimen: Surgical wound (collected ) Gram: No pus cells. Many gram positive cocci, few gram positive bacilli Culture: Isolate 01 Staphylococcus aureus, heavy growth amoxicillin R ciprofloxacin S cefazolin S clindamycin S cloxacillin S cotrimoxazole S tetracycline S vancomycin S

8 Case 1 What antibiotic should you start? What class? What route? How would you monitor response to therapy?

9 Rule #1 Treat the patient, not the lab report

10 Case 2 15m old toddler, male first-born child to social worker and primary school teacher previously healthy, appropriate achievement of ages/stages/ milestones has had fever, irritability, and decreased food intake for >24 hours parents say that the only thing that helps is Tylenol

11 Case 2 physical exam is noteworthy for a healthy-looking child who is crying, febrile (38.1 ), with a dull right tympanic membrane Dx: acute otitis media

12 Case 2 Should you start an antibiotic?

13 Antibiotics and acute otitis media (AOM) whether or not to give antibiotics for AOM is controversial (meaning we don t yet have a clear answer ) practice guidelines around the world vary regarding antimicrobial approach to AOM in Ontario, the Guidelines Advisory Committee recommends ABx for any symptomatic episode of AOM in the Netherlands, guidelines recommend, initially, analgesics alone for symptomatic AOM in children over 6 months of age

14 Estimated antibiotic prescriptions dispensed by 2,000,000 month in Canadian retail pharmacy 1,600,000 1,200, , ,000 0 Jan03 Feb03 Mar03 Apr03 May03 Jun03 Jul03 Aug03 Sep03 Oct03 Nov03 Dec03 p.o. solids p.o. liquids ( kids) Jan04 Feb04 Mar04 Apr04 May04 Jun04 Jul04 Aug04 Sep04 Oct04 Nov04 Dec04 Jan05

15 Antibiotic consumption correlates with resistance Total consumption of macrolide antibiotics by outpatients in Finland from Frequency of resistance to erythromycin among Group A Strep isolates from throatswab and pus samples in Finland in 1990 and NEJM 1997;337:441-6

16 Wait-and-see prescription vs Up-front Abx for AOM one study WASP Standard ABx Prescription randomized 283 kids (age 6m-12y) to either a waitand-see prescription (WASP) of antibiotics or a standard antibiotic prescription 100% 80% 60% 40% 20% 0% Script filled Fever Ear pain Diarrhea JAMA 2006;296:

17 Rule #2 Don t take credit for curing a self-limited disease with antibiotics

18 Other examples of diseases where utility of ABx is questionable sinusitis acute exacerbations of COPD boils (following incision and drainage) endocarditis prophylaxis prior to dental procedures

19 Case 3 57 yo F, store manager history of obesity, diet- and exercisecontrolled DM Type 2, hyperlipidemia, hypertension and hypothyroidism presents to family physician with fever, cough, sputum production, and some mild pleuritic chest pain for 2d

20 Case 3 physical exam noteworthy for: looks generally well (i.e. not in extremis) T 38.6, RR 20, BP 126/78, HR 99 oropharynx clear normal fremitus and percussion, with crackles heard over left lower lung field remainder of exam normal/ unremarkable

21 Case 3

22 Case 3 Diagnosis: Community-acquired pneumonia Should patient be managed as an outpatient or sent to ER? What antibiotic(s) should be used to treat her?

23 Community-acquired pneumonia there are 2 algorithms that are recommended to predict severity of CAP: CURB-65 and Pneumonia Severity Index (PSI) using either of these algorithms, this patient is low risk

24 CURB-65 CURB-65 (Confusion, Urea > 7, RR > 30, BP < 90mmHg systolic or 60mmHg diastolic, age > 65) easy, fast relies on mostly clinical factors... but is unreliable to guide site of care Am J Med 2005;118: Eur Respir J 2006;27:

25 CURB-65 CURB day mortality: 0 0.7% 1 2.1% 2 9.2% % % %

26 PSI stratifies patients into 5 groups a collection of 20 variables, predominantly historical derived from 1 cohort and validated with another cohort uptake has been rather low, but PSI calculators are readily available (e.g. NEJM 1997;336:243-50

27 What antibiotics to use for outpatient CAP the Brits recommend penicillins the Aussies recommend penicillins or doxycycline for low-risk in N. America, macrolide or doxycycline are recommended for very low risk, but with underlying co-morbidities (e.g. heart, lung or renal disease, DM, alcoholism, etc.) a respiratory fluoroquinolone OR a β-lactam + macrolide are recommended

28 Outpatient CAP controversy exists over what is the best choice because: microbiology would suggest covering atypical bacteria (e.g. Legionella, Mycoplasma, and Chlamydophila) is necessary resistance patterns suggest that macrolides are not a great choice cost considerations are a matter of perspective

29 Covering atypical bacteria doesn t seem to matter Number of patients failing to achieve clinical cure or improvement with β lactam antibiotics compared with antibiotics active against atypical pathogens in all cause non-severe community acquired pneumonia BMJ 2005;330:456-62

30 Newer antibiotics are usually more expensive Approximate cost for 5 days treatment: amoxicillin 1g q8h = $10 (generic) doxycycline 100mg bid = $12 (generic) cefuroxime 500mg bid = $20 (generic) azithromycin 500 mg then 250 daily = $22 (generic) clarithromycin 500mg bid = $26 levofloxacin 500mg daily = $28 moxifloxacin 400mg daily = $34 amoxicillin-clav 2g bid = $44

31 New antibiotics might carry a safety risk grepafloxacin removed in 1999 due to safety concerns regarding fatal cardiac arrhythmias sparfloxacin removed in 2001 due to phototoxicity trovafloxacin removed in 2001 due to hepatotoxicity gatifloxacin removed in 2006 due to dysglycaemia gemifloxacin causes rash in 32% of women <40 yrs telithromycin carries a black box warning regarding hepatotoxicity

32 Case 3 Dx: outpatient community-acquired pneumonia amoxicillin or another oral β-lactam (e.g. cephalosporin) seems reasonable guidelines would also support broader coverage (e.g. doxycycline, macrolides + β-lactam, or respiratory fluoroquinolones) but does the patient s CAP risk justify broader/ newer coverage?

33 Rule #3 Don t use broad-spectrum, dangerous, expensive or new antibiotics for treating mild/minor infections

34 Case 4 50 yo M, truck driver currently on disability benefits history of hypertension, hyperlipidemia, smoking (50 pack-years), obesity, asthma and osteoarthritis presents to ER with fever, cough, retrosternal chest pain and SOB x 4 days physical exam largely unremarkable, although looks unwell, has RR/ HR, 38.1 and requires supplemental oxygen

35 Case 4 chest x-ray unremarkable (apart from some evidence of emphysema) CBC: Hb 125 g/l (slightly low), WBC 19.7 x 10 6 /L (high) with neutrophilia, platelets 510 x 10 9 /L (slightly high) chemistry normal urinalysis normal ECG: sinus tachycardia

36 Case 4 Dx: community-acquired pneumonia started on levofloxacin 750mg daily given enoxaparin for DVT prophylaxis after 24hrs afebrile, albeit remains tachycardic and tachypneic--doesn t feel better repeat CXR reported as normal discharged home on levofloxacin 750mg daily, but returns to ER within 8hrs with worsening SOB

37 Case 4 What antibiotics?

38 Case 4 patient was seen by ER doc, who prescribed amoxicillin-clavulanic acid, and was discharged from ER patient went to pharmacy to fill prescription, but suffered a cardiac arrest and died at the pharmacy coroner notified, who ordered an autopsy

39 Case 4 Diagnosis at autopsy: massive pulmonary embolism

40 Rule #4 Don t treat a fever with antibiotics

41 Case 5 66-year-old woman admitted for CAP history of COPD, penicillin allergy and chronic lymphocytic leukemia (not currently requiring Rx) had received a 10d course of ciprofloxacin 6 months earlier and a 10d course of levofloxacin 1 month previously, both for the treatment of an acute exacerbation of COPD

42 Case 5 2 wks before admission, URTI developed. 8d before admission, ciprofloxacin was begun because of respiratory symptoms at admission, her clinical condition had deteriorated, and she was found to have a RLL/RML infiltrate and a small rightsided pleural effusion blood cultures grew S. pneumoniae Rx was switched oral levofloxacin daily

43 Case 5 pleural fluid cultures on the fourth hospital day grew S. pneumoniae. on 5th hospital day, septic shock developed and patient died the following day eventually, testing was performed which demonstrated fluoroquinolone-resistant S. pneumoniae NEJM 2002;346:747-50

44 Case 5 post-mortem testing was performed on the blood and pleural fluid isolates which demonstrated fluoroquinolone-resistant S. pneumoniae NEJM 2002;346:747-50

45 Rule #5 Don t stick with a losing combination

46 Case 6 12 year-old F, at camp, with insect bite to arm subsequent erythema, swelling, warmth and pain surrounding insect bite over course of hours afebrile, stable, feels otherwise well advised by camp MD to go to ER

47 Case 6 WBC 13.5 x 10 6 /L remainder of bloodwork normal started on i.v. cefazolin for 14d for cellulitis... and camp fun was ruined

48 Cellulitis ~ 80% of cellulitis is caused by Group A Streptococcus (most of remainder caused by methicillin-sensitive S. aureus) there is no penicillin-resistant Group A Strep patients rarely get very sick with cellulitis 5 days levofloxacin is as good as 10 days

49 Cellulitis e disease is self-limited and a large majority of the cases get well without any internal medication. I can speak definitely on this point, having, at the Philadelphia Hospital, treated many cases in this way. William Osler, M.D. e Principles and Practice of Medicine: Designed for the use of practitioners and students of medicine. New York, Appleton and Company. 1893

50 Rule #6 i.v. antibiotics should be avoided and remember Rule #2: don t take credit for curing a self-limited disease with antibiotics (although almost all MDs would treat cellulitis with antibiotics)

51 Case 7 39 yo M undergoing radiation therapy for intra-abdominal lymphoma currently on prednisone 20mg daily no prior antimicrobial therapy presented to ER in septic shock, with BP 65/pulse, HR 140, RR 40, T 38.7 oxygen saturation on 100% O 2 by noninvasive positive-pressure ventilation chest x-ray: diffuse white out abdomen rigid... CT abdomen pending

52 Case 7

53 Case 7 Dx: Peritonitis antibiotics? Which ones? what else?

54 Case 7 Perforated appendix with peritonitis. Axial contrastenhanced CT scan shows enhancement and disruption (arrow) of the appendiceal wall. Inflamed bowel wall and severe fat stranding are also present (arrowheads).

55 Peritonitis in an antibiotic-naive patient patient needs surgery +/- drains

56 Peritonitis in an antibiotic-naive patient need to treat gut organisms (gramnegative aerobes and anaerobes, predominantly) many MDs will also want to cover Gram-positives, although probably unnecessary many regimens available

57 Peritonitis in an antibiotic-naive patient amp&gent OR cefotaxime/ceftriaxone OR ciprofloxacin/levofloxacin + metronidazole (OR clindamycin) pip-tazo OR meropenem OR moxifloxacin

58 Rule #7 The best antibiotics are made of steel Rule #8 When the stakes are high, don t be a minimalist

59 Antimicrobial rules to live by treat the patient, not the lab report don t take credit for curing a self-limited disease with antibiotics don t use broad-spectrum, risky, expensive or new antibiotics for treating mild/minor infections don t treat a fever with antibiotics don t stick with a losing combination i.v. antibiotics should be avoided the best antibiotics are made of steel when the stakes are high, don t be a minimalist