Quinolones and urinary tract antiseptics

Question 1

UTI usual organisms

Answer 1

gram -

• E.Coli
• other enterobacteriaceae and pseudomonas

Gram +

• interococci
• group B strep
• coagulase - staph

Question 2

DNA gyrase:

Topoisomerase iV:

Answer 2

gyrase: primary target in gram - bacteria
top: primary target in gram + bacteria

alter the topology of bacterial DNA by introduring or removing supercoils

Question 3

Resistance to fluoroquinolones

Answer 3

• decreased permeability
• efflux pump
• mutation of the enzymes

Question 4

first generation fluoroquinolones

Answer 4

• fluorine at position 6 enhances activity
• norfloxacin, ciprofloxacin, ofloxacin
• improved gram - activity
• GI and urinary infections
• Bactericidal

Question 5

2nd gen and later fluoroquinolones

Answer 5

gatifloxacin- only opthalmic formulation

Levo, moxifloxcin, gemifloxacin- once daliy use for respiratory infections including CA pneumonia

Moxifloxacin- anaerobic

Question 6

fluoroquinolones

absorption:

distribution:

metabolism:

excretion:

Answer 6

absorption: well absorbed orally but bound by divlaent cations that inhibit absorption
distribution: widely distributed, most concentrate in urine
metabolism: hepatic metabolism dimishes activity of norfloxacin and ciprofloxacin
excretion: urinary excretion predominated for first gen FQs

Question 7

Fluoroquinolones

clinical uses

Answer 7

UTI

GI infections

CA/nosocomial pneumonia

osteomyelitis

STI: neisseria gonorrhea and chlamydia

prophylaxis against B. anthracis, N. meningitidis exposure

Question 8

Nitrofurantoin

Answer 8

well absorbed orally

for cystitis only

mech: REduced within bacteria, bind to proteinsand DNA, causing bacterial death
distribution: only active in bladder, not for upper UTI, systemic infection, no tissue penetration

adverse effects:

• GI distress

-acute pneumonitis

• neurological symtoms: neuropathy, nystagmus, headache
• hemolysis in those with G6PD deficiency

Question 9

Fluoroquinolones

adverse effects:

Answer 9

GI: nausea, vomiting common

Hepatotoxicity: severe hepatitis seen with trovafloxacin and removed from market by FDA

hyper and hypoglycermia: especially with gatifloxacin (fomrulation for ystemis use removed from US market in 2006)

• gatifloxacin stimulated insulin secretion and suppresses sysnthesis
• less commonly reported with other FQ

Tendinopathy: rare but black box warning, achilles

Question 10

FQ musculosckeletal toxicity

Answer 10

cartilage concerns

• artropathy reported in animals

tendinopathy

• achilles
• black box

Question 11

FQs and Tx of STIs

Answer 11

Oflaxacin, levofloxacin are alternative drugs for:

• chlamydia- urethritis, cervicitis
• Chancroid- haemophilus durcreyi
• Granuloma inguinale
• Neisseria gonorrheae often reisitent- not recomended

Question 12

FQ summary

Answer 12

very broad antimicrobial spectrum

resistace develops rapidly when used widely

• no longer recommended for gonoccocal infections

Ciprofloxacin- IV and PO. better pseudomonas

Levofloxacin- IV and Po. bettter S. pneumoniae

Moxifloxacin- IV and PO. better S. pneumoniae, anaerobes,

Norfloxacin- PO only, poor systemic activity

CLMC

Question 13

Methenamine

mech:

pharmacokinetics:

drug interactions:

Answer 13

mech action: froms formaldehyde in the bladder

• decomposes at acidic pH below 4.5 from urine
• ineffective for pylonephritis
• ineffective if organisms are urea splitting (proteus)

pharmacokinetics:

• some degraded by gastric acid, most absorbed
• most enter urine via glomerular filtration

formulation:

tablet or oral suspension

Question 14

Methenamine

adverse effects:

drug interactions:

Answer 14

adverse effects:

• GI distress is the major side effect
• high does can cause albuminemia, hematuria and rashes
• overdose associated with hematuria
• contraindicated for: renal dyfunction (mandelis acid may precipitate), hepatic dysfunction (ammonia ions accumulate to cause CNS toxicity)

Drug interactions:

Sulfonamides react chemically with formaldehyde and inactivate both agents

Question 15

Daptomycin

mech:

spectrum:

uses:

administration:

toxicity:

Answer 15

naturally occuring lipopeptide isolated from mold

Mech: inserts into bacterial cell membrane as a polymer, creates K+ channel, disrupting e- gradient, macromolecular synthesis

Rapidly bactericidil

Spectrum:

gram + (staph, strep, enterococcus)

Active against MRSA, VRE.

No gram -

Uses:

skin infections, bacteremia and right sided endocarditis

Inactivated by surfactant in alveoli, not used for pneumonia

administration:

IV only, dosed by weight, once daily

Toxicity:

skeletal myopathy with elevated creatine kinase

Rare eosinophilic pneumonia