Pediatric Infections: Treatment of Resistant Pathogens. Focus : MRSA and DRSP Infections, Including Pneumonia. Blaise L. Congeni M.D.

Transcription

1 Pediatric Infections: Treatment of Resistant Pathogens Focus : MRSA and DRSP Infections, Including Pneumonia Blaise L. Congeni M.D.

2 Patient 1-LP 8 yo with 8 days of fever and 6 days of cough. She had consistently demonstrated fever of about 102. Because of worsening cough and persistent fever the patient was given ceftriaxone and then cefdinir. Because of failure to improve the pt. was admitted.

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7 Patient HPI 16 y/o male, with PMH of exerciseinduced asthma, ADHD, and Asperger syndrome, presents with 4 day hx of SOB. Associated with pressure-like pain in chest and back, worsening with inspiration. Denies fevers, sick contacts, change in asthma sx. ROS positive for nonproductive cough, decreased appetite and possible 5# wt loss over 2-3 weeks PTA

8 Exam and Labs Vitals: 36.2 P66 R18 BP117/40 100% 2L Exam: In NAD, Resp are easy and nonlabored, No rales or rhonchi, no wheezes, S1S2 RRR, no murmurs noted, nailbeds are pink, no pain to palpation of chest Labs: WBC 5.2 with normal diff, ESR 22 CRP 2.74 CXR: WNL O2 was weaned, pt did well

9 Chest CT

10 5 days later Pt is seen by PCP for new onset fever with Tmax 102, left hip/thigh pain, frontal pressure HA that is nonradiating and not associated with N/V, photophobia. Elevated liver enzymes on lab, so a CT of abdomen and pelvis were ordered.

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12 Case of Severe CAP 30 y/o female presents to ER at 0400 with acute fever, cough, dyspnea; recent viral syndrome Severely hypoxic Requires immediate intubation Treated with 3 rd Gen Ceph +

13 Case of Severe CAP Gram stain of ET aspirate reveals GPC in clusters Vancomycin added Patient has multiorgan dysfunction; expires at 1600 CO- MRSA isolated PVL +

14 Community Acquired Pneumonia Akron Children s Guidelines Early, appropriate antibiotic therapy/optimizes clinical outcomes 2. Customized, effective DX & RX strategies must be based on best available evidence 3. Minimizing diagnostic and therapeutic variability is an important goal of guidelines 4. The target population for theses guidelines are: a) Non neonates (>30 of age) b) Immunocompetent c) Immunizations up to date 5. Mycoplasma should be suspected in moderately ill school aged/adolescent patients Draft: many thanks to committee, esp MF and JB

15 No Toxic Appearing (DX) Yes=(Severe Sepsis) Recommended O Optional Θ Not Recommended CXR CBC SpO2 APR* BCX* Rapid Viral Θ Θ O Θ Θ O F/U radiographs not routinely recommended O Suspected Bacterial Pathogen Especially if a. failed b. disease progression Early influenza RX independent of negative rapid result If rapid positive, consider limiting ABX use Suspected mycoplasma (school aged or adolescent) consider Macrolide Toxic Appearing (TX) No 1. Amoxicillin consider Macrolide APR=Acute Phase Reactants PCX=Blood Cx PPE=Parapneumonic Effusion Yes 1. Ceftriaxone MG/KG/day -Consider Azithromycin for school age/adolescent -Consider Vancomycin if: a. 3-6 months b. pneumatocele c. suspected influenza d. sputum/cx suspected staph e. Parapneumonic effusion

16 2010 Antibiogram ORGANISM ANTIBIOTIC Total Streptococcus Pneumoniae Total= 99 Penicillin Ceftriaxone Erythromycin Clindamycin Tetracycline Ofloxacin Vancomycin Sensitive % Intermediate % Resistant % % 80.6% 47.9% 59.6% 62.2% 92.9% 100.0% % 17.3% 0.0% 0.0% 2.0% 6.1% 0.0% % 2.0% 52.1% 40.4% 35.7% 1.0% 0.0%

17 Therapy of S. pneumo Focus: CAP and DRSP Use third generation ceph if local epidemiology documents high-level pen resistance, or life-threatening dis. For oral therapy, amox PK/PD, tolerability more favorable than pen. To cover possibility of RRSP, (MIC-2), use 90 mg/kg/d (3 doses). No oral ceph provides comparable activity to HD amox.

18 Therapy of S. pneumo Focus: CAP and DRSP Significant macrolide resistance is seen in currently available macrolides. For patients with non-serious allergic reactions to amoxicillin, treatment is not well defined, and should be individualized. For more serious allergies treatment options include linezolid, a macrolide, (up to 40% R), or clindamycin.

19 Therapy of S. pneumo Focus: IV amp v ceftriaxone. Ceftriaxone and cefotaxime are substantially more active in vitro than Pne G. Ceftriaxone has been documented to be effective in adults with ceftriaxone R strains. Although no prospective studies exist, iv amp appears as effective as IV ceftriaxone for strains with MICs up to 2 µg/ml.

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21 E test: Utilization of antibiotic concentration gradient

22 MIC= MICs of Vancomycin for S. aureus <0.25 0% 20% 40% 60% 80% 100% 1/1/11-6/21/11 6/ /31/10 6/2009-6/2010* *Vancomycin MIC reported from automated instrument only; no E-test confirmation

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28 Mechanisms of Resistance MRSA Penicillin Binding Proteins Catalyze synthesis of cell wall Site of lactam action inhibit cell wall PBP-2 meca gene synthesizes an altered PBP-2a Lower binding of lactam

29 meca Gene Part of mobile genetic element A genetic element that has the ability to move from one site on a chromosome to another. Staphylococcal cassette chromosome (SCCmec) May harbor other virulence genes or other antibiotic resistance genes

30 CA-MRSA Empiric Treatment Assess disease severity and host Consider resistance issues Obtain cultures

31 TMP/SMX Few studies (Ann Intern Med 1992;117:390-8) Side effects Hypersensitivity rxns Bone marrow suppression No GABHS coverage Resistance potential, but remains low

32 Tetracycline Doxycycline or minocycline Age restriction Resistance in 3% of isolates Some data on use in skin and soft tissue infections No indication for serious disease

33 Clindamycin Resistance S. aureus Clindamycin resistance varies by region 5-25% Macrolide and lincosamide resistance closely related 23S rrna Risk of induced clinda resistance in Erythro resistant strains

34 MLS B Resistance via erm gene No MLS resistance (no erm) ERYTH S; CLINDA - S Constitutive MLS resistance (erm present) ERYTH R; CLINDA - R Possible Inducible resistance ERYTH R; CLINDA S (erm-repressed) ERYTH R; CLINDA S (mef)

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36 CA-MRSA Empiric Treatment Life threatening (e.g. endocarditis, septicemia, toxic shock) lactam antibiotic (e.g. Nafcillin) and Non lactam reliably active against CA- MRSA (Vancomycin) May require additional agents for broader spectrum

37 CA-MRSA Empiric Treatment Moderate localized infections (e.g. osteomyelitis, cellulitis +/- abscess) Incision and drainage when appropriate Consider: Clindamycin Vancomycin Doxycycline ( 8 yrs) TMP/SMX

38 CA-MRSA Empiric Treatment Mild (e.g. simple skin infection) Topical therapy - mupirocin Clindamycin TMP/SMX lactam await culture and clinical response

39 Vancomycin Dosing and Monitoring Adults IV Vanco, mg/kg/dose Q 8-12 hrs. (abw) Not to exceed 2 grams/dose In seriously ill patients with suspected MRSA, consider a loading dose of mg/kg. Consider prolonged infusion, 2 ; antihistamine use Trough levels after the 3 rd dose most accurate way to guide dosing. For most pts with SSTI-1 gram Q 12 hrs. Trough levels rec. for morbidly obese, fluctuating volume of distribution, renal dysfunction. CID 2011:52. pg

40 Vancomycin Dosing and Monitoring Pediatrics IV Vancomycin 15 mg/kg/dose Q 6 hrs. is recommended in children with serious or invasive disease. Consider other issues (NSAIDs, dehydration, use of concomitant antivirals or antimicrobics), and consider modifying dose and additional levels and monitoring renal status. Double Consider Rule also called Law of Unintended Consequences) The efficacy of targeting trough concentrations of µg/ml requires additional study, but should be considered. CID 2011:52 pg 1-38.

41 Linezolid vs Vancomycin in the Management of Nosocomial Pneumonia Phase IV double-blind, RCT 1225 patients enrolled; 448 with MRSA Linezolid 600 mg Q12 vs Vancomcin 15mg/kg Q12 (adjusted for renal function and levels); 7-14 days Linezolid Vancomycin Clinical response (per protocol) 95/165 (57.5%) 81/174 (46.5%) p=0.042 Adverse events 5.2% (anemia) 7.2% anemia * No difference in mortality Kunkle M et al. Abstract LB-49. Annual meeting Infectious Diseases Society America. Vancouver Oct 24, 2010.

42 Outcomes in MSSA Bacteremia Nafcillin vs Vancomycin Prospective Observational Study With 6 Months Follow-up Nafcillin (n=18) Vancomycin (n=70) Persistent >3 but 7 Days 0 Persistent >7 Days 0 Relapse 0 Bacteriologic Failure Chang et al. Medicine (Baltimore). 2003;82:

43 Percent Influence of Vancomycin MIC on Outcome in S aureus Infection MIC Failure Success Moise-Broder et al. Clin Infect Dis. 2004;38:

44 Susceptibility Testing Vancomycin MIC 2 µg/ml indicates susceptibility Vancomycin MIC >2 µg/ml an alternative to vanc should be used, confirm and further characterize. 4-8=VISA; 16=VRSA. Best parameter to predict efficacy of vanc is AUC/MIC (area under curve/minimum inhibitory concentration), determined by measuring trough concentrations

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