Kinder Abx Flashcards
Common Infectious Agents: Outpatient
Streptococcus pneumoniae Mycoplasma pneumoniae Haemophilus influenzae Chlamydophila pneumoniae Respiratory viruses
Common Infectious Agents: Inpatient (non-ICU)
S. pneumoniae M. pneumoniae C. pneumoniae H. influenzae Legionella spp Aspiration Respiratory viruses
Common Infectious Agents: Inpatient (ICU)
S. pneumoniae Staphylococcus aureus Legionella spp Gram-negative bacilli H. influenzae
Infecting Organisms & Disease States
Underlying bronchopulmonary disease:
H. influenzae
Moraxella catarrhalis
+ S. aureus during an influenza outbreak
Chronic oral steroids or severe underlying bronchopulmonary disease, alcoholism, frequent antibiotic use:
Enterobacteriaceae
Pseudomonas aeruginosa
Classic aspiration pleuropulmonary syndrome in alcohol/drug overdose or in seizures with gingival disease or esophageal motility disorders:
Anaerobes
Drug-resistant S. pneumoniae Risk Factors
Age < 2 years or > 65 years B-lactam use within previous 3 months Alcoholism Immunosuppressive illness or therapy Exposure to child at day care
Antimicrobial Coverage for Outpatient, Previously Healthy Pts
Macrolide PO (azithromycin, clarithromycin) Doxycycline PO
Antimicrobial Coverage for Outpatient, At Risk for DRSP
Respiratory fluoroquinolone PO (levofloxacin, moxifloxacin, gemifloxacin)
B-lactam PO [high dose amoxicillin or amoxicillin-clavulanate preferred (alternates: ceftriaxone, cefuroxime)] PLUS a macrolide PO
Antimicrobial Coverage for Outpatient, Regions with high rate (> 25%) of macrolide resistant S. pneumoniae
Consider alternatives
Antimicrobial Coverage for Inpatient, non-ICU
Respiratory FQ IV or PO (levofloxacin, moxifloxacin)
B-lactam IV (ceftriaxone, cefotaxime, or ampicillin preferred) PLUS macrolide IV (azithromycin)
Antimicrobial Coverage for Inpatient, ICU
B-lactam IV (ceftriaxone, cefotaxime, or ampicillin/sulbactam preferred) PLUS azithromycin IV OR a respiratory FQ (levofloxacin, moxifloxacin)
Modified Empiric Regimen for Pseudomonas risks
Structural lung disease (bronchiectasis)
Repeated COPD exacerbations
Frequent corticosteroid and/or antibiotic use
Prior antibiotic therapy
Pseudomonas Risks Treatments
Anti-pseudomonal B-lactam IV (piperacillin-tazobactam, cefepime, imipenem, meropenem) PLUS either ciprofloxacin or levofloxacin Or B-lactam PLUS: An aminoglycoside (gentamicin) AND azithromycin An aminoglycoside AND anti-pseudomonal fluoroquinolone
CA-MRSA risks
End-stage renal disease (dialysis)
Injection drug abuse
Prior influenza
Prior antibiotic use (especially FQ)
CA-MRSA Treatments
Add vancomycin IV or linezolid
Panton-Valentine leucocidin necrotizing pneumonia: add clindamycin or use linezolid
Pseudomonas as MDR
Resistance caused by multiple efflux pumps
Decreased expression of outer membrane porin channel
Increasing resistance to: piperacillin, ceftazidime, cefepime, imipenem, meropenem, aminoglycosides, fluoroquinolones
Other MDRs
Klebsiella intrinsically resistant to ampicillin and can acquire resistance to cephalosporins and aztreonam ESBL production
Enterobacter high frequency of developing resistance to cephalosporins during treatment
These bacteria may carry plasmid mediated AmpC-type enzymes (ESBL) which are carbapenem susceptible but CONCERNED about resistance
May become resistant by loss of an outer membrane porin
MRSA & DRSP
MRSA
> 50% of ICU infections caused by S. aureus methicillin resistant
PBPs with reduced affinity for B-lactams
Concern for linezolid resistance but still rare
DRSP
Altered PBP
ALL MDR strains in US currently susceptible to vancomycin and linezolid
Empiric Therapy – Early Onset
Potential pathogens:
S. pneumoniae
H. influenzae
MSSA
Sensitive gram-negative: E. coli, K. pneumoniae, Enterobacter spp, Proteus spp, Serratia marcescens
Treatment:
Ceftiaxone OR FQ (levofloxacin, moxifloxacin, ciprofloxacin) OR ampicillin/sulbactam OR ertapenem
Empiric Therapy – Late Onset
Potential pathogens (MDR): P. aeruginosa K. pneumoniae (ESBL+) Acinetobacter MRSA Treatment: Antipseudomonal cephalosporin (cefepime, ceftazidime) OR antipseudomonal carbapenem (imipenem, meropenem) OR B-lactam/B-lactamase inhibitor (piperacillin-tazobactam) PLUS Antipseudomonal FQ (ciprofloxacin, levofloxacin) OR aminoglycoside (amikacin, gentamicin, tobramycin) PLUS Linezolid OR vancomycin
Streptococcus pneumoniae
Non-resistant
Penicillin G, amoxicillin
Resistant
Chosen on basis of susceptibility: cefotaxime, ceftriaxone, levofloxacin, moxifloxacin, vancomycin, linezolid
Haemophilus influenzae
Non-B-lactamase producing
Amoxicillin
B-lactamase producing
2nd or 3rd generation cephalosporin, amoxicillin/cluvulanate
Mycoplasma pneumoniae
Macrolide (azithromycin, clarithromycin), tetracycline (doxycycline)
Chlamydophila pneumoniae
Macrolide (azithromycin, clarithromycin), tetracycline (doxycycline)
Chlamydophila psittaci
Doxycycline
Legionella spp
Fluoroquinolone, azithromycin, doxycycline
Enterobacteriaceae (Klebsiella, E. coli, Enterobacter, Proteus)
3rd or 4th generation cephalosporin, carbapenem (if ESBL producer)
Pseudomonas aeruginosa
Antipseudomonal B-lactam PLUS ciprofloxacin, levofloxacin, or an aminoglycoside
Anaerobe (aspiration): Bacteroides, Fusobacterium, Peptostreptococcus
B-lactam/B-lactamase inhibitor, clindamycin
Staphylococcus aureus
Methicillin-sensitive
Antistaphylococcal penicillin (nafcillin, oxacillin, dicloxacillin)
Methicillin-resistant
Vancomycin or linezolid
Pneumocystis jiroveci (P. carinii pneumonia)
Trimethoprim/sulfamethoxazole
Bordetella pertussis
Azithromycin, clarithromycin
Influenza virus
Oseltamivir, zanamivir
Coccidioides spp
No treatment necessary if normal host
Itraconazole, fluconazole
Histoplasmosis and Blastomycosis
Itraconazole
Β-Lactams: MOA
B-lactams are structural analogs of D-Ala-D-Ala; they covalently bind penicillin-binding proteins (PBPs), inhibiting the last transpeptidation step in cell wall synthesis
Β-Lactams: Resistance
Structural difference in PBPs
Decreased PBP affinity for B-lactams
Inability for drug to reach site of action (i.e. gram-negative organisms)
Active efflux pumps
Drug destruction and inactivation by B-lactamases
Penicillins: Adverse effects
Allergic reactions (0.7-10%) Anaphylaxis (0.004-0.04%) Interstitial nephritis (rare) Nausea, vomiting, mild to severe diarrhea Pseudomembranous colitis
Cephalosporins: Adverse effects
1% risk of cross-reactivity to penicillins
Diarrhea
Intolerance to alcohol (disulfram-like reaction due to MTT group of cefotetan)
Carbapenems: Adverse effects
Nausea/vomiting (1-20%)
Seizures (1.5%)
Hypersensitivity
Vancomycin: MOA
Inhibits cell wall synthesis binding with high affinity to D-Ala-D-Ala terminal of cell wall precursor units.
Vancomycin: Resistance
Alteration of D-Ala-D-Ala target to D-alanyl-D-lactate or D-alanyl-D-serine which binds glycopeptides poorly. Intermediate resistance may also occur
Vancomycin: Adverse effects
Macular skin rash, chills, fever, rash
Red-man syndrome (histamine release): extreme flushing, tachycardia, hypotension
Ototoxicity, nephrotoxicity (33% with initial tr > 20 mcg/mL)
Fluoroquinolones: MOA
Concentration-dependent, targets bacterial DNA gyrase & topoisomerase IV. Prevents relaxation of positive supercoils
Fluoroquinolones: Resistance
Mutation in genes encoding DNA gyrase or topoisomerase IV. Active transport out of cell.
Fluoroquinolones: Adverse effects
GI 3-17% (mild nausea, vomiting, abdominal discomfort)
CNS 0.9-11% (mild headache, dizziness, delirium, rare hallucinations)
Rash, photosensitivity, Achilles tendon rupture (CI in children)
30S Inhibitors
Aminoglycosides
ADRs: ototoxicity, nephrotoxicity, neuromuscular block
Tetracyclines
ADRs: GI, superinfections with C. difficile, photosensitivity, teeth discoloration
50S Inhibitors
Macrolides
ADRs: GI, hepatotoxicity, arrhythmia
Clindamycin
ADRs: diarrhea, C. difficile, skin rash
Streptogramins
ADRs: infusion pain and phlebitis
Linezolid
ADRs: myelosuppression, headache, rash
Neurominidase Inhibitors
Oseltamivir (PO), zanamivir (INH)
MOA: analogs of sialic acid, interferes with release of progeny influenza virus from infected host cell
Neurominidase Inhibitors: Adverse effects
Oseltamivir – nausea, vomiting, abdominal pain (5-10%), headache, fever, diarrhea, neuropsychiatric effects
Approved for children ≥ 1 year
Zanamivir – cough, bronchospasm, decrease in pulmonary function (reversible), nasal/throat discomfort, not recommended in underlying airway disease
Approved for children ≥ 7 years
M2 Channel Blockers
Amantadine (PO), rimantadine (PO)
MOA: block M2 proton ion channels of virus inhibiting uncoating of viral RNA within host cell
Active against influenza A only
M2 Channel Blockers: Adverse effects
GI (nausea, anorexia), CNS (nervousness, insomnia, light-headedness), severe behavioral changes, delirium, agitation, seizures
HSV & VZV
Acyclovir (PO, IV, topical), valacyclovir (PO)
MOA: three phosphorylation steps for activation, first step via virus specific thymidine kinase. Inhibits DNA synthesis:
Competition with deoxyGTP for DNA polymerase –> binds DNA template irreversible complex
Chain termination following incorporation into viral DNA
HSV & VZV
Therapeutic use: genital herpes (treatment, prophylaxis, suppression), varicella, HSV encephalitis, neonatal HSV treatment
Adverse effects: nausea, diarrhea, headache
CMV
Ganciclovir (PO, IV), valgancyclovir (PO)
MOA: acyclic guanosine analog, requires activation by triphosphorylation before inhibiting DNA polymerase.
Termination of DNA elongation
CMV
Therapeutic use: CMV retinitis treatment, CMV prophylaxis
Adverse effects: myelosuppression, nausea, diarrhea, fever, peripheral neuropathy
Azole Antifungals
MOA: inhibits fungal cytochrome P450, reducing production of ergosterol
Selective toxicity due to greater affinity for fungal rather than human cytochrome
Azole Antifungals: Therapeutic use
Wide spectrum of activity against Candida spp, blastomycosis, coccidiodomycosis, histoplasmosis, and even Aspergillus (itraconazole, voriconazole)
Azole Antifungals: Adverse effects
Minor GI upset, abnormalities in liver enzymes
Drug interactions!!
Azole Antifungals: drugs
Fluconazole (Diflucan) PO, IV
PK: water soluble, good CSF penetration, high PO bioavailability ~96%
Itraconazole PO
PK: drug absorption increased by food and low gastric pH
Voriconazole (Vfend) PO, IV
PK: well absorbed, bioavailability > 90%
ADRs: visual changes, photosensitivity
Amphotericin B
Polyene macrolide antibiotic
MOA: binds ergosterol and changes permeability of cell by forming pores in cell membrane
PK:
Insoluble in water, variety of lipid formulations available, poorly absorbed PO, t1/2 15 days, only 2-3% of blood level reaches CSF
Therapeutic use: broadest spectrum of activity, useful in life-threatening infections but very toxic
Adverse effects: infusion related (fever, chills, vomiting, headache) and cumulative toxicity (renal damage)
Echinocandins
Caspofungin, micafungin, anidulafungin (IV)
MOA: inhibits synthesis of B(1-3)-glucan, disrupts fungal cell wall, and causes cell death
Therapeutic use: Candida and Aspergillus
Adverse effects: minor GI, flushing
