How Low Can We Go? Readdressing Antibiotic Duration for Common Childhood Infections

Transcription

1 How Low Can We Go? Readdressing Antibiotic Duration for Common Childhood Infections Rebecca Levorson, MD Andrew Nuibe, MD, MSCI Pediatric Infectious Diseases

2 Disclosures Dr. Rebecca Levorson: I have no financial interests to disclose Dr. Andrew Nuibe: I have no financial interests to disclose Duration of therapy should be tailored to each individual case

3 Objectives Review Recommended Duration of Antimicrobial Therapy for Common Childhood Infections including: Group A Streptococcal Pharyngitis CAP Typical & Atypical Cellulitis Acute osteomyelitis UTI Cystitis Pyelonephritis Intra-abdominal Infections Sinusitis Otitis Media Based on Clinical Guidelines and Clinical Studies

4 Background Antimicrobials are the most prescribed medication class in pediatrics 1 Prolonged antimicrobial use has consequences Higher costs Increased risk for adverse outcome, e.g. rash Selects for resistant pathogens 1 Chai G et al. Pediatrics 2012

5 Rationale 20-50% of all antibiotics prescribed in U.S. acute care hospitals are either unnecessary or inappropriate The misuse of antibiotics has also contributed to the growing problem of antibiotic resistance, which has become one of the most serious and growing threats to public health.

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7 In the United States Over 2,000,000 people infected with antibiotic-resistant organisms Approximately 23,000 deaths annually in the United States due to antibiotic resistant infections.

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9 In the United States million courses of antibiotics are written in the outpatient setting yearly. >5 prescriptions/6 people/year in the United States. Local outpatient prescribing practices contribute to local resistance patterns. Azithromycin and amoxicillin are among the most commonly prescribed antibiotics.

10 We Have a PROBLEM!

11 Objectives Review Recommended Duration of Antimicrobial Therapy for Common Childhood Infections including: Group A Streptococcal Pharyngitis CAP Typical & Atypical Cellulitis Acute osteomyelitis UTI Cystitis Pyelonephritis Intra-abdominal Infections Sinusitis Otitis Media Based on Clinical Guidelines and Clinical Studies

12 S.pyogenes Pharyngitis Duration 1940s-1950s: 10 days penicillin studied for prevention of rheumatic fever : 7d versus 10d penicillin PO TID 4 Positive throat culture on follow up at 21 days 7 days PCN (n = 96) 10 days PCN (n=95) 31% 18% 1 Goerner JR et al. NEJM Massell BF et al. JAMA Denny FW et al. JAMA Schwartz RH et al. JAMA 1981

13 S.pyogenes Pharyngitis 1991: 5 days azithromycin versus 10 days penicillin PO q6h 1 Similar improvement and eradication Current U.S. macrolide resistance as high as 50% 2,3 Recommended dosing: 12 mg/kg/dose for 5 days : 6 days amoxicillin BID versus 10 days penicillin PO TID 5 Similar improvement and eradication 1 Hooton TM Am J Med Green M et al. Antimicrob Agents Chemother Martin JM et al. NEJM Shulman ST et al. CID Cohen R et al. PIDJ 1996

14 S.pyogenes Pharyngitis Duration 1997, 1998: 5d cefdinir BID or 5d cefpodoxime BID versus 10 days penicillin PO TID 1,2 Negative throat culture 5d Cefdinir (n=224) 10d PCN (n=216) 5d Cefpodoxime (n=126) 10d PCN (n=130) 90% 72% 75% 76% 1 Tack KJ et al. Arch Pediatric Adol Med Pichichero ME et al. Arch Pediatr Adoles Med 1994

15 S. pyogenes Pharyngitis Duration Conclusions: 10 days of penicillin or amoxicillin recommended first line therapy for optimal eradication 1 < 10 days of amox, azithro, cefdinir, cefpodoxime effective for symptom relief and eradication Unclear whether < 10 days therapy is effective in preventing rheumatic fever 1 Shulman ST et al. CID 2012

16 Objectives Review Recommended Duration of Antimicrobial Therapy for Common Childhood Infections including: Group A Streptococcal Pharyngitis CAP Typical & Atypical Cellulitis Acute osteomyelitis UTI Cystitis Pyelonephritis Intra-abdominal Infections Sinusitis Otitis Media Based on Clinical Guidelines and Clinical Studies

17 Uncomplicated CAP Duration S.pneumoniae considered major bacterial pathogen in immunized, previously healthy 1 10 days of amoxicillin BID is standard, cost-effective choice for S.pneumoniae CAP 1,2 1 Bradley JS et al. CID Lorgelly PK et al. Eur Resp J 2010

18 Uncomplicated CAP Duration 2002, 2004: 3d vs 5d Amoxicillin TID 1,2 Similar clinical outcomes but ~20% had RSV 2014: 3d vs 10d, 5d vs 10d amoxicillin 3 5 days non-inferior to 10 days Treatment failure 3 d Amoxicillin (n=10) 5 d Amoxicillin (n=56) 10 d Amoxicillin (n=59) Pakistan Multicentre Amoxicillin Short Course Therapy (MASCOT) pneumonia study group. Lancet ISCAP Study Group. BMJ Greenberg D et al. PIDJ 2014

19 Uncomplicated CAP Duration Conclusions: 10 days of amoxicillin recommended for mild-tomoderate S.pneumoniae CAP days of amoxicillin 90 mg/kg/day is acceptable for mild outpatient CAP 1 Be wary of using oral cephalosporins and macrolides for S.pneumoniae CAP 1 Bradley JS et al. CID 2012

20 Atypical CAP Duration Mycoplasma pneumoniae CAP Azithromycin 3 d at 10/kg vs. 5 d at 10/kg x1 then 5/kg x 4 d

21 Objectives Review Recommended Duration of Antimicrobial Therapy for Common Childhood Infections including: Group A Streptococcal Pharyngitis CAP Typical & Atypical Cellulitis Acute osteomyelitis UTI Cystitis Pyelonephritis Intra-abdominal Infections Sinusitis Otitis Media Based on Clinical Guidelines and Clinical Studies

22 Uncomplicated Cellulitis Duration Typically due to S. aureus and S. pyogenes Increasing cellulitis incidence in MRSA era 1 Wide variation in management for SSTIs 2,3 2004: 5d vs 10d levofloxacin for cellulitis 4 Similar clinical outcomes in both groups 2016: < 7 days for non-suppurative cellulitis 5 Therapy < 7 days not associated with higher recurrence cf. longer therapy 1 Dukc VM et al. PLoS One Mistry RD et al. Acad Emerg Med Moore SJ et al. PIDJ Hepburn MJ et al. Arch Int Med Shuler CL Pediatrics 2016

23 Uncomplicated Cellulitis Duration Conclusions: 5 days of therapy for S. aureus and S. pyogenes acceptable for uncomplicated cellulitis 1 Can extend duration if not improving 1 Stevens DL et al. CID 2014

24 Objectives Review Recommended Duration of Antimicrobial Therapy for Common Childhood Infections including: Group A Streptococcal Pharyngitis CAP Typical & Atypical Cellulitis Acute osteomyelitis UTI Cystitis Pyelonephritis Intra-abdominal Infections Sinusitis Otitis Media Based on Clinical Guidelines and Clinical Studies

25 Acute Osteoarticular Infection Duration 1967: Arbitrarily treated for 5 weeks 1 Thought that debrided bone took 4 weeks to revascularize 2 Parenteral therapy < 3 weeks tied to chronic disease 3,4 Typically treat pyogenic arthritis for 2-3 weeks and osteomyelitis for 4-6 weeks 1 Green JH. Br Med J Lazzarini L et al. J Bone Joint Surg Dich VQ et al. Am J Dis Child O Brien et al. J Bone Joint Surg 1982

26 Acute Osteoarticular Infection Duration 1997: 3-4 wks of 1G cephalosporin or clindamycin for acute S.aureus osteomyelitis 1 No treatment failure or long term sequelae 2009: 10d vs 30d 1G cephalosporin or clindamycin for S.aureus pyogenic arthritis 2 No treatment failure with shorter course if initial clinical response was robust 1 Peltola et al. Pediatrics Peltola et al. CID 2009

27 Acute Osteoarticular Infection Duration Conclusions: Pyogenic arthritis can be treated for days if initial robust response Osteomyelitis can be treated for 3-4 weeks if initial robust response

28 Objectives Review Recommended Duration of Antimicrobial Therapy for Common Childhood Infections including: Group A Streptococcal Pharyngitis CAP Typical & Atypical Cellulitis Acute osteomyelitis UTI Cystitis Pyelonephritis Intra-abdominal Infections Sinusitis Otitis Media Based on Clinical Guidelines and Clinical Studies

29 Urinary Tract Infections

30 Pediatric UTIs Pyuria + Positive Urine Culture 85% E. coli AAP guidelines 2011 (2 mo to 2 years) UA + antibiogram initial empiric therapy Increasing MDRO UTIs in USA (esp. DC area)

31 Lower UTIs 1981: 1 d vs. 10 d: short course less effective in preventing recurrent infection , 2012: No difference in persistent bacteriuria or recurrence between 2-4 days and 7-14 days of oral antibiotics. 2,3 2011: Adult guidelines suggest 3-5 days antibiotics 4 1 McCracken et al., Pediatrics 1981; 67; Michael M, et al., Short versus standard duration oral antibiotic therapy for acute urinary tract infection in children. Cochrane Database Syst Rev 2003; 1:CD Fitzgerald A, et al., Antibiotics for treating lower urinary tract infection in children. Cochrane Database Syst Rev 2012; 8: CD Gupta K, et al., CID 2011:52, 5:e

32 Acute Pyelonephritis and Febrile UTIs IV oral vs. all oral antibiotics for 14 days no difference in renal scarring or recurrence rates even in bacteremia 1, day courses inferior to 7-10 day courses for febrile UTIs 3, 4 Ongoing NIH sponsored trial for 5 days vs. 10 days for febrile UTI, Acute Pyelonephritis in kids 1 Bocquet N, et al. Randomized trial of oral versus sequential IV/oral antibiotic for acute pyelonephritis in children. Pediatrics 2012; 129:e Hoberman A, et al., Oral versus initial intravenous therapy for urinary tract infections in young febrile children. Pediatrics 1999; 104: Grimwood K, et al., N Z Med J 1988; 24;101 4 AAP 2011: UTI clinical practice guidelines; Pediatrics

33 Pediatric UTI Treatment Conclusions Uncomplicated cystitis: 3-5 days Febrile UTI & Pyelonephritis: IV vs. po equal 7-14 days current AAP guidelines Awaiting NIH sponsored study results 5 vs. 10 days for pediatric pyelonephritis

34 Objectives Review Recommended Duration of Antimicrobial Therapy for Common Childhood Infections including: Group A Streptococcal Pharyngitis CAP Typical & Atypical Cellulitis Acute osteomyelitis UTI Cystitis Pyelonephritis Intra-abdominal Infections Sinusitis Otitis Media Based on Clinical Guidelines and Clinical Studies

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36 Complicated intraabdominal infection, adequate source control, randomized to antibiotics for 2 days after resolution of fever, leukocytosis, and ileus with max of 10 days (control) vs. 4+/- 1 day of antibiotics Approximately 4 days were similar to those after a longer course of antibiotics (approximately 8 days) that extended until after the resolution of physiological abnormalities. Sawyer RG, et al., N Engl J Med 2015;372:

37 Intra-abdominal Infections 1. Uncomplicated appendicitis (without perforation) Single perioperative dose of antibiotics (eg., cefoxitin) 2. Complicated appendicitis 4-7 days antibiotics sufficient Ceftriaxone/metronidazole can be given as once daily doses No difference between longer and shorter duration as long as adequate source control Low complication rates if IV antibiotics are stopped when patients are afebrile and tolerating diet 3. Abscessed Appendicitis If source control, as above If no source control planned, longer duration typical (~10-14 days) No specific duration recommendations Complicated Intra-abdominal Infection Guidelines CID 2010:50 (15 January)

38 Objectives Review Recommended Duration of Antimicrobial Therapy for Common Childhood Infections including: Group A Streptococcal Pharyngitis CAP Typical & Atypical Cellulitis Acute osteomyelitis UTI Cystitis Pyelonephritis Intra-abdominal Infections Sinusitis Otitis Media Based on Clinical Guidelines and Clinical Studies

39 Acute Bacterial Sinusitis Definition Acute URI with: Persistent illness (nasal discharge [of any quality] or daytime cough or both lasting more than 10 days without improvement) OR A worsening course (worsening or new onset of nasal discharge, daytime cough, or fever after initial improvement) OR Severe onset (concurrent fever >102.2 F and purulent nasal discharge for at least 3 consecutive days) Wald E, et al., Pediatrics 2013; 132; e262

40 Acute Bacterial Sinusitis Pathogens Estimated proportions in ABS based on middle ear infections 1 S. pneumoniae (30% cases) H. influenzae (30% cases) M. catarrhalis (10% cases) 25% sterile cultures 1 Casey JR, et al., PIDJ 2010

41 Acute Bacterial Sinusitis Treatment AAP Recommended duration: 7 days after symptom resolve with minimum duration of 10 days 1 IDSA Recommended duration: days 2 14% Placebo cure rate 3 1 Wald E, et al., Pediatrics 2013; 132; e262 2 Chow AW, et al., CID 2012;54; Wald E, et al., Pediatrics 2009; 124; 9

42 Objectives Review Recommended Duration of Antimicrobial Therapy for Common Childhood Infections including: Group A Streptococcal Pharyngitis CAP Typical & Atypical Cellulitis Acute osteomyelitis UTI Cystitis Pyelonephritis Intra-abdominal Infections Sinusitis Otitis Media Based on Clinical Guidelines and Clinical Studies

43 Acute Otitis Media Pathogens same as Acute Bacterial Sinusitis 2004 AAP Guidelines help with AOM diagnostic criteria, watch/wait 10 day course derived from S.pyogenes pharyngitis therapy : Augmentin BID 5d or 10d versus Augmentin TID 2 5 d not as effective, especially in < 2 yo 1 Lieberthal AS et al. Pediatrics Hoberman A et al. PIDJ 1997

44 Who to treat? Start Antibiotics Severe <2 yo Nonsevere bilateral <2 yo Close Observation OR Start Antibiotics Nonsevere Unilateral < 2yo Nonsevere AOM >2 yo

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46 Acute Otitis Media Duration Majority due to bacteria 1 Standard 10 day course derived from S.pyogenes pharyngitis therapy : 5d versus 10d Augmentin BID 3 5 days Augmentin (n=197) 10 days Augmentin (n=178) Clinical cure at days % 69% 1 Jacobs Dr et al. Antimicrob Agents and Chemother Lieberthal AS et al. Pediatrics Hoberman A et al. PIDJ 1997

47 Acute Otitis Media Duration 2001: Antibiotics for 5, 7, or 10 days 5 days (n=707) 7 days (n=423) 10 days (n=1042) All ages Cured + Improved 82% 82% 83% 2 yo Cured + Improved 75% 73% 76% Pichichero ME et al. Otolaryngol Head Neck Surg 2001

48 Casey JR, et al., Ped Infect Dis J Aug;32(8):805-9.

49 Acute Otitis Media Duration Conclusions: < 2 yo should get 10 days of amoxicillin 2-5 yo can get 7 days of amoxicillin > 6 yo can get 5-7 days of amoxicillin Be wary of using oral cephalosporins and macrolides for S.pneumoniae 1 1 Lieberthal AS et al. Pediatrics 2013

50 USA: 34% Strep pneumo macrolide resistance 17% Strep pneumo Penicillin resistance

51 Acute Otitis Media Duration AOM incidence and epidemiology changing s/p PCV vaccine Marom et al. JAMA Pediatr 2014

52 Summary Opportunities remain to determine optimal length of therapy for many infections Thoughtfully consider the patient s response to therapy Return for Re-evaluation vs. Finish the Whole Bottle Educate Everyone including Patients and Parents as Antibiotics are a Shared Resource

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54 PSV Pediatric Infectious Diseases Dr. Daniel Keim Dr. Rebecca Levorson Dr. Katherine Moyer Dr. Andrew Nuibe Dr. Brittany Goldberg