Antibiotics II handout

Antibiotics II Glycopeptides Aminoglycosides Macrolides “The Mycins” Margaret K. Hostetter, M.D.

Vancomycin +

+ requires addition

of an aminoglycoside

THE GLYCOPEPTIDES

B. fragilis

Gut

GRAM NEGATIVES

Mouth

Ps.aerug

Pseud spp

Serratia

Enterobacter

Klebsiella

E. coli

H. flu

Meningococcus

Grp A strep

Pneumo

Enterococcus

Grp B strep

Listeria

St. aureus

St. epi

GRAM POSITIVES ANAEROBES

B. fragilis

Gut

Mouth

Ps.aerug

ANAEROBES Pseud spp

Serratia

Enterobacter

Klebsiella

E. coli

H. flu

Meningococcus

Grp A strep

GRAM NEGATIVES Pneumo

Enterococcus

Grp B strep

Listeria

St. aureus

St. epi

GRAM POSITIVES

SIDE EFFECTS of VANCOMYCIN

VANCOMYCIN-RESISTANT ENTE ROCOCCI

HISTAMINE-RELEASE Infusion in < 1 hour • flushed skin • angioneurotic edema • hypotension

NEPHROTOXICITY or OTOTOXICITY RARE

Risk Factors for Health Care Acquired MRSA • MRSA252 • Hospitalized on antibiotics or frequently hospitalized (e.g. cystic fibrosis) • Previous colonization - patient or family • Long-term care facility - patient or family • Respiratory therapy - patient or family • Dialysis - patient or family • Serious infections susceptible only to Vancomycin, Daptomycin, Linezolid Emerg Infect Dis 11(6) 2005

Risk Factors for Community Acquired MRSA (CA-MRSA) • • • •

USA300 >> USA400 ~5% of children are carriers NO RISK FACTORS Crowding, sharing of personal items: sports teams, military facilities, correctional facilities, child care • Skin condition (e.g. eczema) • Differing susceptibilities: TMP-SMX, clindamycin, doxycycline

D-Test for Inducible Clindamycin Resistance

E

E

C

C

Resistant Organisms in YNHH 40% 35% 30% 25% 20% 15% 10% 5% 0% *3/91- *3/92- '93 2/92 2/93 VRE*

'94

'95

MRSA

'96

'97

'98

CipR Pseudomonas

'99

'00

'01

'02

CeftazR Klebsiella

'03

'04

'05

Treatment of MRSA Drug

CSF

Blood

Lungs

Bones/ Joints

Nafcillin Cephs Vanco

√ at 60/kg

Clinda Bactrim

√

+

If susceptible If susceptible If susceptible but not ABE, SBE

Linezolid

√

√ but not ABE, SBE

Daptomycin

√

√

√

√

√

Penicillin Resistance in Pneumococci Drug

Susceptible Intermediate µg/ml µg/ml

Resistant µg/ml

PO penicillin

2.0

IV penicillin non-meningeal

8.0

IV penicillin meningeal

0.12

3˚ cephs non-meningeal

4.0

3˚ cephs meningeal

2.0

Treatment of Penicillin Resistant Pneumococci Drug

CSF

Blood

Lungs

PO

√

√

Amox

Immunocompetent

Immunocompetent

√

√

Immunocompetent

Immunocompetent

√

√

PCN (all)

Ceph 2˚, 3˚

Clinda

Except endocarditis

Vanco

√ + rifampin

√

Increase dose to 60 mg/kg/day

√

±

Ceftin Clinda

Case Study A 60-day-old female infant presents with temperature to 39.5˚ C rectally, poor feeding, and lethargy. Physical exam is normal except for lethargy and fever. Blood culture is drawn. Urinalysis and CXR are normal. CSF shows 100 WBC’s (90% PMN’s, 10% lymphs), glucose 40/90, protein 175. • Differential diagnosis? • Possible causative organisms? • Antibiotic regimens?

Antibiogram for Meningitis in Infants 2 -36 mos Possible Cause

Penicillin

Group B strep

PCN, ampicillin

Strep pneumoniae

All unless resist.

Cephalosporin 3˚ 3˚ unless resist.

Aminoglycoside

Other

---

Vanco

---

Vanco

H. influenzae Ampicillin type b (only ~75%)

3˚

---

---

Meningococcus

3˚

---

---

PCN, ampicillin

Therefore, the regimen for meningitis in any child 2 months of age or older is

Vancomycin PLUS Cefotaxime or Ceftriaxone

Vancomycin Levels • Not generally indicated (Clin ID 1994;18:533-43) • Used for patients with fluctuating renal function or chronic renal failure • PEAK 20-40 µg/ml; now shoot for 40µg/ml • TROUGH 10-15 µg/ml

Vancomycin: Not a Wonder Drug • Very confined spectrum • Poorer anti-staphylococcal activity than Nafcillin in endocarditis (AAC 1990; 33:1227-1231) • Very poor penetration into lung and bone (AAC 1988; 32:1320-1322) • Advantages – Staphylococcus epidermidis or MRSA – Penicillin-allergic patients – Acceptable penetration into CSF (shunts, meningitis 2˚ penicillin resistant pneumococci) but at higher dosage (60 mg/kg/day)

Case Study Administration of IV Vancomycin (plus other agents where necessary) is required for which of the following scenarios? • antibiotic-associated colitis that has failed to respond to metronidazole √ • initial therapy of meningitis in a 10-year-old • routine surgical prophylaxis for line insertion √ • prophylaxis for urethral dilatation in a 13 month-old infant with corrected tetralogy of Fallot • initial therapy of pneumococcal otitis media in a vomiting patient √ • initial therapy of a respiratory decompensation in a 6 monthold tracheotomized child known to carry MRSA

Case Study A 6-year old boy who did not receive varicella vaccine is hospitalized with an area of erythema and induration extending for a diameter of 5 cm. around a pox. Aspirate of the advancing border grows group A streptococci and Staph aureus. The empiric therapy of choice is • aqueous penicillin G • aqueous penicillin G plus Vancomycin √ • Vancomycin • Clindamycin • Imipenem

Case Study A 6-year old boy who did not receive varicella vaccine is hospitalized with an area of erythema and induration extending for a diameter of 5 cm. around a pox. Aspirate of the advancing border grows group A streptococci and Staph epidermidis. The therapy of choice is √ • aqueous penicillin G alone • aqueous penicillin G plus Vancomycin • Vancomycin alone • Imipenem

When Is Staph epi a Pathogen? Blood cultures of neonates with lines in place Confirm with culture of peripheral blood before Abx Blood cultures of other patients with lines in place Confirm with culture of peripheral blood before Abx Cultures of CSF in symptomatic patients with ventricular shunts

Blood cultures of patients with prosthetic valves or patches in the heart Cultures of implants in patients with prosthetic joints

The Aminoglycosides

• Gentamicin • Tobramycin • Amikacin

of a peniclllin

+ - requires addition

Amikacin

+ Gentamicin

+ Tobramycin

B. fragilis

Gut

GRAM NEGATIVES

Mouth

Ps.aerug

Pseud spp

Serratia

Enterobacter

Klebsiella

E. coli

H. flu

Meningococcus

Grp A strep

Pneumo

Enterococcus

Grp B strep

Listeria

St. aureus

St. epi

GRAM POSITIVES ANAEROBES

B. fragilis

Gut

Mouth

Ps.aerug

ANAEROBES Pseud spp

Serratia

Enterobacter

Klebsiella

E. coli

H. flu

Meningococcus

Grp A strep

GRAM NEGATIVES Pneumo

Enterococcus

Grp B strep

Listeria

St. aureus

St. epi

GRAM POSITIVES

SIDE EFFECTS of the AMINOGLYCOSIDES TRUE ALLERGY RARE NEPHROTOXICITY

OTOTOXICITY

RESPIRATORY

Associated with • Hypotension • Loop diuretics • Vancomycin • Liver disease

High-tone frequencies

Curare-like effects with IV push Treat with calcium

HIGH TROUGH

Vestibular

HIGH PEAK

Aminoglycoside Levels • Gentamicin/Tobramycin – PEAK 5-10 µg/ml – TROUGH < 2 µg/ml

• Amikacin – PEAK 20-30 µg/ml – TROUGH