Community Acquired Pneumonia: An Update on Guidelines

Transcription

1 Community Acquired Pneumonia: An Update on Guidelines Claudia Summa, BScPhm Pharmacy Resident September 12, 2006

2 Objectives To give a brief description of the pathophysiology of community acquired pneumonia (CAP) To discuss the various organisms that cause CAP To discuss the clinical settings with increased risk of pathogens To show which drugs treat CAP bugs To compare the old MSH guidelines to the new MSH guidelines To show evidence supporting these changes To compare side effects, drug interactions, convenience, and cost of the various antibiotics used to treat CAP

3 Pathophysiology Organisms can gain access to the lower respiratory tract via: o o o inhalation, bloodstream aspiration Changes in the pulmonary defence may increase the likelihood of infection: Cough reflex can be impaired by stroke, neuromuscular disease, sedatives, s or poor nutrition Mucociliary transport is depressed with the aging process, tobacco smoking, dehydration, morphine, atropine, prior infection with influenza virus, and chronic bronchitis. Anatomic changes such as emphysema, bronchiectasis,, and obstructive mass lesions prevent clearance of microbes.

4 Organisms Causing CAP Streptococcus Pneumoniae Haemophilus influenzae Mycoplasma pneumoniae Chlamydia pneumoniae Other agents include: S. aureus,, group A streptococci, Moraxella catarrhalis, Legionella species, Gram negative bacilli, anaerobes, and viruses, including respiratory syncytial virus, influenza virus, and parainfluenza virus.

5 Clinical Settings with Increased Risk of Pathogens Alcoholism anaerobes, gram-negative bacilli COPD/smoker H. influenzae, M. catarrhalis Increased age/co-morbid medical conditions Gram negative bacilli Recent hospitalizations Gram negative bacilli, S. aureus, Legionella species, anaerobes Nursing home Gram negative bacilli, H. influenzae, S. aureus, C. pneumoniae, anaerobes

6 DRUGS that fight CAP BUGS Macrolides S. pneumoniae, Mycoplasma pneumoniae, Chlamydia pneumoniae, Legionella species (azithromycin( and clarithromycin), H. influenzae (azithromycin and clarithromycin) Fluoroquinolones S. pneumoniae, Legionella species, H. influenzae Amoxicillin, Amoxicillin/Clavulanic acid S. pneumoniae, Moraxella catarrhalis or H. influenzae 2 nd or 3 rd generation cephalosporins S. pneumoniae,, aerobic gram negative bacilli, H. influenzae Clindamycin S. pneumoniae, anaerobes Metronidazole anaerobes

7 Outpatient Therapy Without Modifying Factors OLD GUIDELINES Erythromycin 500mg PO q6h Azithromycin 500mg PO on day 1, then 250mg PO od f4d Clarithromycin 500mg PO q12h NEW GUIDELINES Azithromycin 500mg PO on day 1, then 250mg PO od f4d Clarithromycin 500mg PO q12h Clarithromycin XL 1000mg PO od * Alternative: Doxycycline 100mg PO q12h Alternative: Doxycycline 100mg PO q12h Moxifloxacin 400mg PO od Levofloxacin mg PO od * = Non-formulary

8 Outpatient Therapy With Modifying Factors OLD GUIDELINES Amoxicillin/clavulanic clavulanic acid 500mg/125mg PO q8h Cefuroxime 500mg PO q12h Cefprozil 500mg PO q12h One of the above plus: Azithromycin 500mg PO on day 1, then 250mg PO od f4d Clarithromycin 500mg PO q12h Single Therapy: Levofloxacin 500mg PO od Moxifloxacin 400mg PO od NEW GUIDELINES Amoxicillin/clavulanic clavulanic acid 875mg/125mg PO q12h * Amoxicillin/clavulanic clavulanic acid 500mg/125mg PO q8h Amoxicillin 1000mg PO q8h One of the above plus: Azithromycin 500mg PO on day 1, then 250mg PO od f4d Clarithromycin 500mg PO q12h Clarithromycin XL 1000mg PO daily * Single Therapy: Levofloxacin mg PO od Moxifloxacin 400mg PO od

9 Inpatient Therapy Admission to a Hospital Ward OLD GUIDELINES AL Amoxicillin/clavulanic clavulanic acid 500mg125mg PO q8h Plus Azithromycin 500mg PO on day 1, then 250mg PO od f4d Clarithromycin 500mg PO q12h Single Therapy: Levofloxacin 500mg PO od NEW GUIDELINES AL Amoxicillin/clavulanic clavulanic acid 875mg/125mg PO q12h * Amoxicillin/clavulanic clavulanic acid 500mg/125mg PO q8h Amoxicillin 1000mg PO q8h Plus Azithromycin 500mg PO on day 1, then 250mg PO od f4d Clarithromycin 500mg PO q12h Clarithromycin XL 1000mg PO od * INTRAVENOUS Ceftriaxone 1g IV q24h plus Azithromycin 500mg IV od f5d Levofloxacin 500mg IV od Single Therapy: Moxifloxacin 400mg PO od INTRAVENOUS Ceftriaxone 1g IV q24h plus Azithromycin 500mg IV od f5d Moxifloxacin 400mg IV od

10 Inpatient Therapy Macro- Aspiration OLD GUIDELINES AL Amoxicillin/clavulanic clavulanic acid 500mg/125mg PO q8h INTRAVENOUS Ceftriaxone 1g IV q24h with Metronidazole 500mg IV q12h NEW GUIDELINES AL Amoxicillin/clavulanic clavulanic acid 875mg/125mg PO q12h * Amoxicillin/clavulanic clavulanic acid 500mg/125mg PO q8h INTRAVENOUS Ceftriaxone 1g IV q24h with Metronidazole 500mg IV q12h

11 Inpatient Therapy: Admission to an ICU OLD GUIDELINES Ceftriaxone 1g IV q24h with Azithromycin 500mg IV od NEW GUIDELINES Ceftriaxone 1g IV q24h with Azithromycin 500mg IV od Alternative: Ceftriaxone 1g IV q24h with Levofloxacin 500mg IV/PO od Alternative: Ceftriaxone 1g IV q24h with Moxifloxacin 400mg IV/PO od

12 Inpatient Therapy Admission to an ICU (Modifying Factors) OLD GUIDELINES Bronchiectasis Piperacillin/Tazobactam 4.5g IV q8h with Tobramycin 5mg/kg IV od NEW GUIDELINES Bronchiectasis Piperacillin/Tazobactam 4.5g IV q8h with Ciprofloxacin 400mg IV/750mg PO q12h Suspected or confirmed Pseudomonas aeruginosa: Piperacillin/Tazobactam 4.5g IV q8h with Tobramycin 5mg/kg IV od PLUS Azithromycin 500mg IV od or Levofloxacin 500mg IV od Suspected or confirmed Pseudomonas aeruginosa: Piperacillin/Tazobactam 4.5g IV q8h with Tobramycin 5mg/kg IV od PLUS Azithromycin 500mg IV od or Moxifloxacin 400mg IV/PO od

13 Evidence For Addition of High Dose Amoxicillin Aubier M, Verster C, Regamey P, et al. Once-Daily Sparfloxacin Versus High Dosage Amoxicillin in the Treatment of Community-Acquired, Suspected Pneumococcal Pneumonia in Adults.. Clinical Infectious Disease. 1998; 26: One year, multi-center, randomized, double- blind trial comparing the efficacy and safety of once-daily sparfloxacin and a 1-g 1 tid dosage of amoxicillin Out of 329 enrolled patients, 159 were randomized to receive sparfloxacin and 170 to receive amoxicillin

14 Evidence for Addition of High Dose RESULTS: Amoxicillin /2 Average duration was 10.8 days Both drugs were effective in the intent-to to-treat treat and evaluable population at both endpoints Overall rates of success among evaluable patients were equivalent between drugs, both at the end of treatment (sparfloxacin( sparfloxacin,, 92%; amoxicillin, 87%) and at follow-up (sparfloxacin( sparfloxacin,, 89%; amoxicillin, 84%) Sparfloxacin was well tolerated and produced fewer gastrointestinal side effects than amoxicillin

15 Resistance of Fluoroquinolones Emergence of S. pneumoniae with reduced susceptibility to the fluoroquinolones (FQ) has been described in Canada, Spain, Hong Kong, eastern and central Europe and to a lesser extent, the United States Resistance is primarily due to mutations in the genes encoding the target topoisomerase enzymes In Canada, Chen et al found that ciprofloxacin-resistant resistant pneumococci increased from 0% in 1993 to 1.7% in In adults the prevalence was 0% in 1993 to 3.7% in 1998 In 2002, the Canadian Bacterial Surveillance Network reported a prevalence of levofloxacin-resistant pneumococci of 4% in sputum isolates recovered from patients over 65 years of age

16 Evidence for High Dose, Short Course Levofloxacin Dunbar LM, Wunderink RG, Habib MP, et al. High-Dose, Short- Course Levofloxacin for Community-Acquired Pneumonia: A New Treatment Paradigm. Clinical Infectious Diseases. 2003; 37: Multi-center, randomized, double-blind blind trial Compared levofloxacin dosages of 750mg/ day for 5 days with 500mg/day for 10 days for the treatment of mild to severe CAP Out of 530 patients enrolled, 256 patients received levofloxacin 750mg/day IV/PO for 5 days and 272 patients received levofloxacin 500mg/day IV/PO for 10 days

17 Evidence for High Dose, Short Results: Course Levofloxacin /2 At post-therapy therapy assessment, the clinical success rates in the clinically evaluable population were 92.4% for the 750mg group and 91.1% for the 500mg group Microbiological eradication rates were 93.2% and 92.4% in the 750mg and 500mg groups, respectively. Authors concluded that the short course, high dose regimen of levofloxacin was at least as effective and well tolerated for the treatment of mild to severe CAP as 500mg of levofloxacin per day for 10 days.

18 Side Effects and Drug Interactions of the Various Antibiotics Macrolides Side effects include: abdominal cramping, nausea, vomiting, diarrhea,, rash Drug interactions include: warfarin, digoxin,, cyclosporine, benzodiazepines, carbamezapine Doxycycline Side effects include: nausea, vomiting, photosensitivity Drug interactions include: calcium, magnesium, iron, phenytoin, phenobarbital Amoxicillin, Amoxicillin/Clavulanic acid Side effects include: hypersensitivity reactions, rash, nausea, vomiting Fluoroquinolones Side effects include: abdominal pain, headache, dizziness, photosensitivity Drug interactions include: calcium, warfarin, theophylline, cyclosporine Ceftriaxone Side effects include: hypersensitivity reactions, rash, nausea, vomiting, pain at the injection site Metronidazole Side effects include: vertigo, headache, abdominal cramps, diarrhea,, vomiting, taste alterations Drug interactions include: ethanol, warfarin

19 Convenience and Cost of the Various Antibiotics Macrolides Dosing: QID (E), BID (C), OD (A and C) Cost: E - $0.80 A - $3.52 (PO), $20.50 (IV) C - $5.92 Doxycycline Dosing: BID Cost: $0.56 Amoxicillin, Amoxicillin/Clavulanic acid Dosing: BID, TID Cost: $0.66 (A) $1.56 (A/C) Fluoroquinolones Dosing: BID (C), OD (M, L) Cost: C - $1.22 (PO), $57.02 (IV) M - $3.40 (PO), $28.90 (IV) L - $4.00 (500mg PO), $7.55 (750mg PO), $34.00 (IV) Ceftriaxone Dosing: OD Cost: $34.00 Metronidazole Dosing: BID Cost: $0.44 (PO), $2.58 (IV) Cost in terms of per day

20 References 1. Mandell LA, Bartlett JG, et al. Update of the Infectious Diseases of Society S of America Guidelines for the management of community-acquired pneumonia in immunocompetent adults. Clinical Infectious Diseases. 2003; 37: Mandell LA, Marrie TJ, Grossman RF, et al. Canadian guidelines for the initial management of community acquired pneumonia: an evidence-based update by the Canadian Thoracic Society. The Canadian Community-Acquired Pneumonia Working Group. Clinical Infectious Diseases. 2000; 31: University Health Network. Guidelines for Antimicrobial Use. Antibiotic A Subcommittee of the Pharmacy and Therapeutics Committee. Revised Feb University Health Network. Guidelines for Antimicrobial Use. Antibiotic Subcommittee of the Pharmacy and Therapeutics Committee. Revised Sept Chen D, McGeer A, de Azevedo J et al. Decreased susceptibility of Streptococcus pneumoniae to fluoroquinolones in Canada. Canadian Bacterial Surveillanc Network. New England Journal of Medicine. 1999; 341: Aubier M, Verster R, Regamey C, et al. Once-daily sparfloxacin versus high dosage amoxicillin in the treatment of community-acquired, suspected pneumococcal pneumonia in adults. Clinical Infectious Diseases ; 26: Dunbar LM, Wunderink RG, Habib MP, et al. High-Dose, Short-Course Levofloxacin for Community-Acquired Pneumonia: A New Treatment Paradigm. Clinical Infectious Diseases. 2003; 37: Marrie TJ. Community-acquired Pneumonia. In: Gray, J. Therapeutic Choices. Ottawa: Canadian Pharmacists Association; 2003: Wells BG, DiPiro JT, Schwinghammer TL, Hamilton CW. Respiratory Tract Infections, Lower. In: Pharmacotherapy Handbook 6 th Edition. New York: McGraw-Hill Publishing; 2006: