Antibacterial drugs

Question 1

Major mechanisms of resistance:

Answer 1

 Enzymatic: e.g. penicillinase, carbapenemase

 Target changes : e.g., PBP 2 to PBP 2a

 Porin closure , especially in GNB

 Efflux pumps exist. * Dicloxacillin induces increased clearance of coumadin;
Carbapenems reduce serum concentrations of valproic acid

Question 2

 Mechanism of MRSA Resistance:

Answer 2

 Change from PBP 2 to PBP 2a; Controlled by mecA or (rarely) mec
C genes

Question 3

Special Toxicities of Oxacillin and

Nafcillin

Answer 3

Allergy: to include Interstitial Nephritis

Additional unique toxicity:
Oxacillin: Hypersensitivity hepatitis
Nafcillin: Neutropenia after weeks of therapy

Question 4

Vancomycin

 Three types of resistance:

Answer 4

 Hetero-
 VISA
 High level resistance due to target change.

Question 5

 Somewhat unique Vanco family AEs:

Answer 5

 Vancomycin (esp.with gent) &Telavancin:
Nephrotoxicity

 Vanco IgA bullous dermatitis

 Telavancin: Dysgeusia and Teratogenic

 Daptomycin: Potential muscle toxicity and eosinophilic pneumonia

Question 6

Salvage therapies for dapto-resistant MRSA

Answer 6

 Nafcillin, oxacillin, or ceftaroline restores negative charge on cell membrane and thereby reverse daptomycin resistance

Question 7

Cephalosporin “Generations”

Answer 7

Sixth (Ceftolozane/Tazo): ESBL producing GNBs

Seventh (Ceftaz/Avibactam): (ESBL producing GNBs) & KPCs

Question 8

Blactamases- Important subsets:

Answer 8

ESBLs,

Amp C, &

Carbapenemases

Question 9

AmpC Beta-Lactamases:

 Chromosomal and inducible in SPICE-M enterobacteriaceae

Answer 9

SPICE-M bacteria:

Serratia, 
Providencia/Pseudomonas, 
indolepositive Proteus, 
Citrobacter, 
Enterobacter, 
Morganella.

 Greatest risk is repressed gene in Enterobacter sp

Question 10

Cephalosporin AEs/Failures

Answer 10

 Seizures (can be akinetic with cefepime)

 Pseudo-choledocholithiasis (Ceftriaxone)

Question 11

Drugs with useful activity vs carbapenemase-producing GNB

Serine (non-metallo): KPC (Class A) & OXA-48 et al

Answer 11

Polymyxins

Ceftazidime/avibactam

Meropenem/vaborbactam

Question 12

Drugs with useful activity vs carbapenemase-producing GNB

Metallo-carbpenemase (zinc) : VIM, New Dehli MetalloBlasé, and IMP

Answer 12

Polymyxins

 Aztreonam

 Minocycline

Sulbactam (Acinetobacter baumannii)

Question 13

AZTREONAM (monobactam)

cross allergenicity . . .

Answer 13

> Safe in patients with severe IgE mediated Pen/Ceph.allergy

> only cross allergenicity is with ceftazidime

Question 14

Salvage Tx for GNB co-producing ESBL and metalo-carbapenase

Answer 14

 Can use Ceftazidime-avibactam plus aztreonam

Question 15

Fosfomycin:

 Susceptibility

Answer 15

 Many Enterobacteriaceae , including ESBL producing Enterobacteriaceae

 Not susceptible:
 Non-fermentative GNBs: ,Acinetobacter, Burkholderia, Pseudomonas,
Stenotrophomonas
 Carbapenemase producers

Question 16

Linezolid

Significant AE’s

Answer 16

 Mitochondrial Toxicity after 2 + weeks of therapy:

> Reversible bone marrow suppression
Lactic acidosis
Peripheral neuropathy
Irreversible optic neuropathy !

Question 17

Which classes of antibacterials achieve therapeutic levels in the prostate ?

Answer 17

Fluoroquinolones

Trimethoprim-sulfamethoxazole

Question 18

Once-daily dosing of aminoglycosides works because of:

Answer 18

Concentration-dependent killing

Long Post-antibiotic effect

Long “Time off” that allows renal, vestibular, and cochlear cells to excrete accumulated drug.

Result: Better efficacy, less toxicity

Question 19

Purpose of Aminoglycoside

Serum Drug Levels

Answer 19

Peak levels are obtained to ensure efficacy

Trough levels are obtained to minimize risk of toxicity

Question 20

TMP-SMX: Spectrum

 Primary Choice:

Answer 20

 CA-MRSA SSTI

 Stenotrophomonas

 Coxiella (in pregnancy)

 Nocardia

 Pneumocystis

 Mycobact. marinum

 Cyclospora, Cystoisospora, Toxo.

Question 21

Nitrofurantoin significant AE’s

Answer 21

Pulmonary toxicity with chronic therapy:
desquamative interstitial pneumonia with
fibrosis

Intrahepatic cholestasis and hepatitis

DRESS syndrome: drug rash, eosinophilia, & systemic symptoms;

Question 22

Late Reactions to Penicillins

Answer 22

 Coombs positive hemolytic anemia
 Neutropenia, thrombocytopenia
Serum sickness, Interstitial nephritis
 Hepatitis
Eosinophilia
 Drug fever

Question 23

Differential Diagnosis of

Thrombocytopenia for ID docs

Answer 23

 Margination in capillary beds during bacteremia
 Heparin associated antibody
 Consumption during active hemorrhage
 Bone marrow failure
 Inadequate thrombopoietin due to hepatic failure
 Drug-induced immune thrombocytopenia: e.g., vancomycin,
nafcillin, tmp/smx, piperacillin-tazobactam, rifampin

Question 24

Mechanism of resistance for VRSA

Answer 24

D-ala- target changes to D-lac target

Question 25

Macrolides resistance;

> two most common mechanisms

Answer 25

> Target site alteration; encoded by the ermB gene; MoCo in Europe

> Efflux pump encoded by the mef A (macrolide efflux) gene. MoCo in USA