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

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• rganisms/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 RX

Pop Quiz

• Is it MSSA or MRSA?

Methicillin Sensitive Staph Aureus (MSSA)

• Coagulase (+)
• Catalase (+)
• Oxacillin sensitive
• SSTI, PNA, Meningitis, Endocarditis, Osteomyelitis
• 1st Line:
• Penicillinase-resistant Penicillin (Nafcillin, Oxacillin)
• 1st 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
• 1st line: Vancomycin (MIC ≥2  switch agent)
• Alternatives
• Daptomycin (not for PNA)
• Linezolid (for SSTI, PNA)
• Tigecycline (not for bacteremia)
• Ceftaroline

Table 1. MRSA Treatment Options

*for Community Acquired MRSA (CA-MRSA) ᵃSalvage therapy

Oral Treatment IV Treatment TMP-SMX* Clindamycin* Doxycycline, minocycline* Linezolid Vancomycin Linezolid Daptomycin Ceftaroline Tigecyclineᵃ Quinupristin-dalfopristinᵃ Dalbavancin, oritavancin

Methicillin Resistant Staph Aureus (MRSA)

Vancomycin, Daptomycin, and Linezolid

• All active against gram-positive cocci, including MRSA

Agent Adverse reactions Pearls Vancomycin Infusion reactions, renal toxicity (not contraindicated in AKI), ototoxicity (rare) MIC ≥ 2 associated with treatment failure Do not use in MSSA infections (unless penicillin allergy) Daptomycin CPK elevation (obtain baseline and monitor weekly) Inactivated by pulmonary surfactant  do not use for pneumonia Linezolid Bone marrow suppression, peripheral neuropathy, optic neuritis, lactic acidosis Long-term therapy increases risk

• f AE’s

Not ideal in UTIs (~30% excreted in urine) Table 2. Gram-Positive Drug Class Overview

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
• xacillin, 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?

a)

Daptomycin 6 mg/kg intravenously once daily

b) Linezolid 600 mg intravenously twice daily c)

Vancomycin 1 g intravenously twice daily

d) Ceftriaxone (1 g/d intravenously) plus azithromycin (500

mg/d intravenously)

e)

Vancomycin (15-20 mg/kg intravenously twice daily) to 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
• Vancomycin is the drug of choice for empiric coverage
• Ampicillin is the drug of choice for enterococcus if susceptible
• E. faecalis
• E. faecium

More common Highly virulent Less resistance Less common Less virulence More resistance  VRE

Table 4. Usual treatment options based on species

*Active against E. faecium but not E. faecalis; salvage therapy

Vancomycin-Resistant Enterococcus

VRE (E. Faecalis) VRE (E. Faecium) Pen G or ampicillin Linezolid Daptomycin Tigecycline Fluoroquinolones Cystitis only: nitrofurantoin, fosfomycin, doxycycline Daptomycin Linezolid Quinipristin/dalfopristin* Tigecycline Cyctitis only: fosfomycin, doxycycline

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

• Piperacillin/ Tazobactam

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

Pop Quiz

• A. Piperacillin/tazobactam

B.

Aztreonam

C.

Cefepime

• D. Meropenem

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?

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 Ampicillin/ sulbactam 3.1 g q6h IV 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

• f the following carbapenems would you avoid the most in this

patient?

a)

Ertapenem

b) Meropenem c)

Imipenem/cilastin

d) Doripenem

Case Question

• OC is a 42 year-old female with PMH of HTN presenting for

complaints of increased urinary frequency and 4/10 suprapubic pain. No fevers and PE is normal. UA shows WBC 17, (+)leukocyte esterases and urine culture shows > 105 cfu/mL ESBL E. coli in the urine.

• PMH: Afib (on Warfarin, Amiodarone)
• Which outpatient treatment agent could you consider for this

patient?

a)

Meropenem

b)

Levofloxacin

c)

Fosfomycin

d)

Bactrim

e)

No treatment indicated

Carbapenem-Resistant Enterobacteriaceae

RISK FACTORS Broad spectrum antibiotic use Trauma Diabetes Indwelling urinary/ venous catheters Mechanical ventilation Immunocompromised – malignancy, severe illness, organ transplant

• includes 70 different genera from Enterobacteriaceae with

various mechanisms to become resistant to carbapenems

• Usual type of infections: VAP, UTI, IAI
• Exhibit resistance to most beta-lactam antibiotics
• Optimal treatment is largely unknown

Carbapenem-Resistant Enterobacteriaceae

Class A (KPC) Klebsiella producing carbapenemase Class B (NDM-1) New Delhi Metalloproteases Class D OXA Can be transmitted from Klebsiella to other genera Most common in US Dependence on Zinc for efficient hydrolysis of betalactams Inhibited by EDTA Very mobile genetic element Hydrolyze oxacillin Heterogenous class 6 subgroups produce carbapenemase not susceptible to betalactam inhibitors Variable response to betalactam inhibitor

Carbapenem-Resistant Enterobacteriaceae

Carbapenem-Resistant Enterobacteriaceae

Polymyxins Colistin

• prodrug; slow conversion
• renal dose adj

Polymyxin B

• active drug
• no renal dose adj
• achieve higher peak

concentrations Most active agent in vitro Possible resistance development with monotherapy ADV: Neurotoxicity*** Nephrotoxicity (>40%) Tigecycline In vitro activity Increased resistance developing Most effective when used in combination Fosfomycin I: uncomplicated UTI Achieve high urinary concentration for prolonged time period Concentration after single dose persist above MIC after 72hrs Aminoglycosides I: uncomplicated UTI Good clinical data in UTI but failed therapy with bloodstream infection

Combination: Colistin+ Tigecycline + Meropenem extended infusion (2g q8h over 3hrs)

• Lower mortality rate than monotherapy (27% VS 38%)
• Advantage:
• Reduction of initial inappropriate therapy
• potential synergistic effects
• suppression of emerging resistance
• Disadvantage
• Increased adverse effects
• Development of Clostridium difficile infection

Carbapenem-Resistant Enterobacteriaceae

Carbapenem-Resistant Enterobacteriaceae

Colistin Polymyxin B Form administered Prodrug Active drug Time until maintenance dose 12-24 hours 12 hours Maintenance dose Determined by CrCl Lower doses Determined by MIC Higher doses Renal adjustment Yes No Adverse Events Nephrotoxicity (50-60%) Neurotoxicity Nephrotoxicity (20-40%) Neurotoxicity Pearls Most studied for CRE UTI use: achieves higher concentrations in urine May be safer compared to colistin

Promising Drug: Ceftazidime- Avibactam

• possible activity against class A, Class B, class D Betalactamase
• Avibactam  activity against KPCs and OXA, but no activity on

NDM1

• ADV: N/V/ constipation, anxiety

Carbapenem-Resistant Enterobacteriaceae

ANTIMICROBIAL STEWARDSHIP

• Having an antimicrobial stewardship program (with certain components)

is required by the Joint Commission

• MCH antimicrobial stewardship program supported by administration

and the members include:

• Infectious disease physician: Dr. Mocherla
• Pharmacy leader: Erica Wilson, Lindsay Rumold
• Pharmacists, laboratory personnel, nurses, physicians, and infection

control staff

Antimicrobial Stewardship

• What we do
• Infectious disease rounds (Tuesdays and Thursdays) with Dr. Mocherla
• Monitor and report resistance patterns and antibiotic use
• Projects to improve use of antibiotics
• Collect data and report stewardship activities to appropriate committees

Antimicrobial Stewardship Resources

• Antimicrobial Stewardship Pocket Guide
• Completed, printed and distributed, and printed as posters
• Can also be found on intranet SharePoint site
• Includes Antibiogram and Antibiotic Use Algorithms
• CAP, HAP, VAP, aspiration PNA, acute bacterial skin and skin structure

infections, UTIs, complicated intra-abdominal infections, complicated intra- abdominal infections

• New pathways to be added:
• Clostridium difficile infections
• Meningitis
• Febrile neutropenia
• endocarditis

Antimicrobial Stewardship Resources

• Antimicrobial Stewardship SharePoint Site on MCH Intranet
• Navigate:
• MCH Home Page > Employee Links (left hand side) > "Antimicrobial Stewardship“
• Follow Link:
• https://echdo365.sharepoint.com/department/AS/default.aspx?apr=1&wa=w

signin1.0

• The following resources will be available on the site:
• Infectious Disease Guidelines and Resources, MCH Antibiogram, MCH Empiric

Antibiotic Use Algorithms, Antibiotic Dosing, Educational Presentations, Infection Control Committee Reports, and Policies & Procedures

References

• Centers for Disease Control and Prevention. Antibiotic resistance threats in the

United States. 2013 Atlanta, GA: CDC;2013.

• Huttner A. Antimicrobial resistance and infection control. Nov 18 2013;2(1):31.
• Arnold R et al. (2011). Emergence of Klebsiella pneumoniae Carbapenemase (KPC)-

producing bacteria. South Med J, 104(1) 40-45. doi:10.1097/SMJ.0b013e3181fd7d5a.

• Rossolini G et al. (2005). Treatment and control of severe infections caused by

multiresistant Pseudomonas aeruginosa. Clin Microbiol Infect, 11(4): 17-32.

• Morril H et al (2014). Treatment options for Carbapenem- Resistant

Enterobacteriaceae infections. DOI: 10.1093/ofid/ofv050

• John Hopkins antibiotics guide. (2017). Unbound Medicin. [Mobile application

software]. Retrieved from https://www.hopkinsguides.com/Hopkins.