INFECTIOUS DISEASE ANTIMICROBIAL REVIEW Michelle Aguirre Janel - PowerPoint PPT Presentation

INFECTIOUS DISEASE ANTIMICROBIAL REVIEW Michelle Aguirre Janel Liane Cala PGY1 Pharmacy Practice Residents Medical Center Hospital

Objectives • Review basic microbiology of organisms • Implement MCH Antibiogram utilization • Define minimum inhibitory concentration (MIC) • Discuss resistant drug organisms and treatment • Identify risk factors for common multi-drug resistant pathogens

INTRODUCTION

Bacterial Morphology https://www.slideshare.net/drsameh16/bacterial-staining-42157535

Gram Staining http://ib.bioninja.com.au/options/untitled/b1-michttp://ib.bioninja.com.au/options/untitled/b1-microbiology-organisms/gram-staining.htmlology organisms/gram-staining.html

ANTIBIOGRAM, MIC INTERPRETATION

MCH Antibiogram • Printed each year based on previous year’s laboratory data for critical care and medical floors • Provided by pharmacy department and the antimicrobial stewardship program • Should be reviewed and used to determine proper empiric therapy based on most common organisms seen in different types of infections

MIC Interpretation • MIC: minimum inhibitory concentration • Lowest concentration of an antibiotic that inhibits the growth of a given strain of bacteria • Susceptibility Interpretation • S (sensitive): organism is inhibited by the serum concentration of the drug that is achieved using recommended dosage • I (intermediate): isolates with MICs that approach usually attainable blood and tissue levels and for which response rates may be lower than for susceptible strains • R (resistant): resistant to the usually achievable serum drug levels

Case Question • VE is a 44-year-old man who was admitted for an abscess. He was started on empiric therapy with pipercillin/tazobactam and vancomycin. Which de-escalation is appropriate based on the following susceptibilities?

PATHOGEN DIRECTED R X

Pop Quiz • Is it MSSA or MRSA?

Methicillin Sensitive Staph Aureus (MSSA) • Coagulase (+) • Catalase (+) • Oxacillin sensitive • SSTI, PNA, Meningitis, Endocarditis, Osteomyelitis • 1 st Line: • Penicillinase-resistant Penicillin (Nafcillin, Oxacillin) • 1 st Generation Cephalosporins (Cefadroxil, Cefazolin, Cephalexin) • Alternatives: • Clindamycin, Vancomycin, Tetracycline, Sulfamethoxazole-trimethoprim

Methicillin Resistant Staph Aureus (MRSA) • Coagulase (+) • Catalase (+) • Oxacillin resistant • SSTI, PNA, Meningitis, Endocarditis, Osteomyelitis • 1 st line: Vancomycin (MIC ≥2  switch agent) • Alternatives • Daptomycin (not for PNA) • Linezolid (for SSTI, PNA) • Tigecycline (not for bacteremia) • Ceftaroline

Methicillin Resistant Staph Aureus (MRSA) Table 1. MRSA Treatment Options Oral Treatment IV Treatment TMP-SMX* Vancomycin Clindamycin* Linezolid Doxycycline, minocycline* Daptomycin Linezolid Ceftaroline Tigecycline ᵃ Quinupristin-dalfopristin ᵃ Dalbavancin, oritavancin *for Community Acquired MRSA (CA-MRSA) ᵃSalvage therapy

Vancomycin, Daptomycin, and Linezolid • All active against gram-positive cocci, including MRSA Table 2. Gram-Positive Drug Class Overview Agent Adverse reactions Pearls Vancomycin Infusion reactions, renal MIC ≥ 2 associated with toxicity (not contraindicated treatment failure in AKI), ototoxicity (rare) Do not use in MSSA infections (unless penicillin allergy) Daptomycin CPK elevation (obtain Inactivated by pulmonary surfactant  do not use for baseline and monitor weekly) pneumonia Linezolid Bone marrow suppression, Long-term therapy increases risk peripheral neuropathy, optic of AE’s neuritis, lactic acidosis Not ideal in UTIs (~30% excreted in urine)

Case Question • A 33-year-old obese man with a history of recurrent skin abscesses due to MRSA presents to the emergency department with a productive cough, pleuritic chest pain, and dyspnea. One week ago he had influenza. Chest radiography shows multilobar infiltrates and early cavitation. A sputum Gram stain shows numerous gram-positive cocci in clusters. • The sputum culture grows S. aureus, which is resistant to oxacillin, has MIC of 6 to vancomycin, and greater than 4 to clindamycin and which are susceptible to daptomycin, linezolid, and quinupristin/dalfopristin.

Case Question (continued) • Which one of the following antimicrobial regimens would be the best treatment for this patient’s infection? Daptomycin 6 mg/kg intravenously once daily a) b) Linezolid 600 mg intravenously twice daily Vancomycin 1 g intravenously twice daily c) d) Ceftriaxone (1 g/d intravenously) plus azithromycin (500 mg/d intravenously) Vancomycin (15-20 mg/kg intravenously twice daily) to e) achieve a trough concentration of 10 to 15 µg/mL plus clindamycin (600 mg intravenously every 8 hours)

Enterococcus • Gram-positive bacteria in short chains (may appear as streptococcus in pairs/chains in gram-stain report) • Present in normal colonic flora, oropharyngeal and vaginal secretions • Usually a nosocomial, opportunistic pathogen E. faecalis E. faecium More common Less common Highly virulent Less virulence More resistance  VRE Less resistance • Vancomycin is the drug of choice for empiric coverage • Ampicillin is the drug of choice for enterococcus if susceptible

Vancomycin-Resistant Enterococcus Table 4. Usual treatment options based on species VRE (E. Faecalis) VRE (E. Faecium) Pen G or ampicillin Daptomycin Linezolid Linezolid Daptomycin Quinipristin/dalfopristin* Tigecycline Tigecycline Fluoroquinolones Cyctitis only: fosfomycin, Cystitis only: nitrofurantoin, doxycycline fosfomycin, doxycycline *Active against E. faecium but not E. faecalis; salvage therapy

Pseudomonas aeruginosa • Gram-negative, non-fermenting rod • Usually a nosocomial, opportunistic pathogen • Usual infections • Respiratory: pneumonia • GU: UTI/pyelonephritis • CV: endocarditis, bacteremia, sepsis • Skin/bone: cellulitis, osteomyelitis • Risk factors: • Immunosuppression, diabetes mellitus, cystic fibrosis, neutropenia, AIDS

Treatment Options for Pseudomonas Betalactams Aminoglycosides Fluoroquinolones Polymyxin PCN Amikacin Ciprofloxacin 400 mg Colistin -Piperacillin/ Tazobactam 8 mg/kg THEN q8h 5mg/kg x1 7.5 mg/kg q12h Levofloxacin 750 mg THEN Cephalosporins q24 2.5mg/kg q12 Ceftazidime 2g q8 Gentamicin/ Cefepime 1-2g q8 Tobramycin Polymyxin B Ceftazidime/Avibactam 2.5g 3 mg/kg THEN 1.25 mg/kg q12 q8h 2 mg/kg q8h Ceftolozane/tazobactam 1.5g q8h Carbapenems Imipenem/Cilastatin 1g q8h OTHER: Meropenem 1g q8h Fosfomycin 3g Doripenem 500mg q8h PO x 1 Monobactam Aztreonam 2g IV q8h

Pop Quiz Patient on piperacillin/tazobactam for 4 days treating HAP and WBC 25, febrile, requiring pressors. Which intravenous antimicrobial agents would be appropriate for a patient with this susceptibility report? A. Piperacillin/tazobactam Aztreonam B. Cefepime C. D. Meropenem

Acinetobacter • Gram negative, strictly aerobic, nonmotile, coccobacilli • Commonly found in: soil, water, catheters, ventilation equipment • Usual types of infection: PNA, Septicemia, Burn Wounds • Risk factors: • Immunosuppression • Burns • Medical devices (central line, catheter, ventilator, endoscopes, feeding tubes) • Previous antibiotic exposure

Acinetobacter treatment • Imipenem 0.5-1gm IV q6h • Meropenem 0.5-2 gm IV q 8h • Ampicillin/ Sulbactam 3g (2:1) q6h • Tigecycline 100 mg IV, then 50 mg IV q 12 h • Pan-resistant isolates: • Colistin + any of the above • Variable activity  AMG, Cephalosporins, Minocycline, Rifampin, TMP/SMX

STENOTROPHOMONAS MALTOPHILIA • Aerobic, gram negative bacillus with polar flagella • Found mostly in aquatic environment, plants, soil; frequent colonizer of body fluids • Nosocomial sources: dH2O, nebulizers, dialysates, contaminated disinfectants • Low virulence  mostly affects immunocompromised • Risk factors: • Foreign bodies (catheters) • Neutropenia • Broad spectrum abx • CF

STENOTROPHOMONAS MALTOPHILIA Trimethoprim/sulfamethoxazole 15mg/kg/day divided in 2 to 3 doses Ticarcillin/clavulanate 3.1 g q6h IV Ampicillin/ sulbactam 3 g q6h IV Ceftazidime 2 g q8h IV Ciprofloxacin 400 mg q8-12h IV Levofloxacin 500-750 mg q24h IV Moxifloxacin 400mg/day Doxycycline 100 mg q12h IV Colistin (MDR) + COMBI 2.5 mg/kg q12

ESBL (Extended Spectrum Betalactamase)

ESBL (Extended Spectrum Betalactamase)

• Carbapenems- similar outcomes and mortality within class • Ceftolozane- Tazobactam** RENAL IAI  1.5g q8h 4-14d + Metronidazole  • cUTI  1.5g q8h x 7days (at least**) • • Ceftazidime-avibactam** RENAL IAI  2.5g q8h 5-14d + Metronidazole • cUTI  2.5g q8h x 7days (at least**)- 14d • • Cefepime 2g q8h – variable; not suggested; inferior to carbapenem • Piperacillin- Tazobactam- variable; not recommended • Fluoroquinolones- Cipro  • Uncomplicated UTI- Fosfomycin, Nitrofurantoin, Bactrim

Pop Quiz • JW is a patient who is being seen for an intra-abdominal ESBL infection. In addition, he has a history of poorly controlled seizures for which he takes several antiepileptic drugs. Which of the following carbapenems would you avoid the most in this patient? Ertapenem a) b) Meropenem Imipenem/cilastin c) d) Doripenem