Antibiotics II Glycopeptides Aminoglycosides Macrolides “The Mycins”

Antibiotics II

GlycopeptidesAminoglycosides

Macrolides“The Mycins”

Margaret K. Hostetter, M.D.

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GRAM POSITIVES GRAM NEGATIVES ANAEROBES

THE GLYCOPEPTIDES

Vancomycin +

+ requires addition of an aminoglycoside

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SIDE EFFECTS of VANCOMYCIN

HISTAMINE-RELEASE

Infusion in < 1 hour • flushed skin • angioneurotic edema • hypotension

NEPHROTOXICITY orOTOTOXICITY RARE

VANCOMYCIN-RESISTANTENTEROCOCCI

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, LinezolidEmerg 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

EC

C

Resistant Organisms in YNHH

0%

5%

10%

15%

20%

25%

30%

35%

40%

*3/91-2/92

*3/92-2/93

'93 '94 '95 '96 '97 '98 '99 '00 '01 '02 '03 '04 '05

VRE* MRSA CipR Pseudomonas CeftazR Klebsiella

Treatment of MRSA

Drug CSF Blood Lungs Bones/

Joints

Nafcillin

Cephs

Vanco √ at 60/kg √ +

Clinda

Bactrim

If susceptible but not

ABE, SBE

If susceptible If susceptible

Linezolid √ √ but not

ABE, SBE

√ √

Daptomycin √ √ √

Penicillin Resistance in Pneumococci

Drug Susceptibleµg/ml

Intermediateµg/ml

Resistantµg/ml

PO penicillin <0.06 0.12-1.0 >2.0

IV penicillin non-meningeal

<2.0 4.0 >8.0

IV penicillinmeningeal

<0.06 None >0.12

3˚ cephsnon-meningeal

<1.0 2.0 >4.0

3˚ cephsmeningeal

<0.5 1.0 >2.0

Treatment of Penicillin Resistant Pneumococci

Drug CSF Blood Lungs PO

PCN (all) √ Immunocompetent

√Immunocompetent

Amox

Ceph 2˚, 3˚

√Immunocompetent

√ Immunocompetent

Ceftin

Clinda √Except endocarditis

√ Clinda

Vanco √+ rifampin

√ ±

√ Increase dose to 60 mg/kg/day

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 Cephalo-

sporin

Amino-

glycoside

Other

Group B

strep

PCN,

ampicillin

3˚ --- Vanco

Strep pneumoniae

All

unless resist.

3˚

unless resist.

--- Vanco

H. influenzae

type b

Ampicillin

(only ~75%)

3˚ --- ---

Meningo-coccus

PCN, ampicillin

3˚ --- ---

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)

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 month-

old tracheotomized child known to carry MRSA

Case Study

√

√

√

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

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

Cultures of CSF in symptomatic patients with ventricularshunts

Cultures of implants in patients with prosthetic joints

The Aminoglycosides

• Gentamicin

• Tobramycin

• Amikacin

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+

+ - requires addition of a peniclllin

+Tobramycin

Amikacin

Gentamicin

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SIDE EFFECTS of the AMINOGLYCOSIDES

TRUE ALLERGY RARE

NEPHROTOXICITY

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

OTOTOXICITY

High-tone frequencies

Vestibular

RESPIRATORY

Curare-like effects with IV pushTreat with calcium

HIGH TROUGH

HIGH PEAK

Aminoglycoside Levels

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

• Amikacin – PEAK 20-30 µg/ml– TROUGH <10 µg/ml

Aminoglycoside Levels

• Patients at risk for nephrotoxicity– Fluctuating renal function, usually 2˚ BP

instability– Other nephrotoxic agents -e.g. Vancomycin– Liver disease

• When to do trough: just before third dose• When to do peak: 1 hour after third dose• PEAK - correlates with efficacy, ototoxicity• TROUGH - correlates with nephrotoxicity

How to Adjust

• Adjust the dosage interval, not the individual dose, in order to retain the peak

• Rough rule of thumb– If pt’s creatinine is 2X normal, increase the

dosing interval 2-fold (e.g. from 8 to 16 hours)– If pt’s creatinine is 3X normal, increase the

dosing interval 3-fold (e.g. from 8 to 24 hours)

Case Study

A three-year old girl with a neurogenic bladder has a history of recurrent urinary tract infections. Six weeks ago she was treated with Cefotaxime for a resistant E. coli. She now presents with fever and blood and urine cultures growing Pseudomonas aeruginosa, sensitive to Ticarcillin and Gentamicin. On a dose of Ticarcillin of 300 mg/kg/day and Tobramycin, 2.5 mg/kg/dose, her Tobramycin levels are as follows:

• Tobra peak of 8.0 and trough of 3.0• Tobra peak of 3.0 and trough of 0.4• Tobra peak of 13.0 and trough of 1.0

• Discuss the implications of each of these levels in terms of adequacy of treatment, risk for nephrotoxity or ototoxicity, and changes in management.

Case Study

A 16-year-old boy under treatment for ALL presents to the ED with 6 hours of fever, onset about 7 days after his last chemotherapy. Physical exam shows a Broviac catheter and an enlarging black lesion on his thigh. His WBC count is 2,000 with <10% PMN’s.



Antibiogram for Sepsis in the Immunocompromised Host

Possible Causes Penicillins Cephalosporins Penicillin Allergy

Gram +St epi/aureus, GAS, oral strep, Enterococci

Nafcillin 1˚, 2˚, 3˚ exceptCeftaz

Bactrim? ClindamycinVancomycin

Gram –E. coli, Klebsiella Enterobacter, Ps aeruginosa

Ticar/clav (Timentin)Pip/tazo (Zosyn)

1˚, 2˚, 3˚ Aminoglycoside

Fungi --- --- ---

When Do You Need “Double Coverage” for Gram Negatives?• When treating Pseudomonas aeruginosa with

Ticarcillin or Piperacillin---requires Gent or Tobra for synergy

• When choosing empiric therapy for a patient with fever and neutropenia/neutrophil dysfunction and shock

• As an empiric regimen for an immunocompromised patient possibly infected with GNR (CSF, blood, lungs, urine, other sterile sites)

When Don’t You Need “Double Coverage” for Gram Negatives?• When treating an uncomplicated non-

pseudomonal infection in a normal host (e.g. UTI, pyelo, osteo, cellulitis)– Cefotaxime– Ceftazidime– Aminoglycoside– Fluoroquinolone

• N.B. When treating Pseudomonas aeruginosa with Ticarcillin or Piperacillin in a normal host, it’s advisable to add an aminoglycoside

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Azithromycin

Mycoplasma,

Chlamydia

ClindaC. difficile

Case Study

An 18-month-old unvaccinated male infant presents with two days of fever, cough, and increasing work of breathing. CBC shows a WBC count of 35,000 with 80% PMN’s. CXR shows a lobar infiltrate in the left lower lobe. A blood culture is drawn and the child is admitted.



• Antibiotic regimens if he has anaphylaxis to penicillin?

Antibiogram for Community Pneumonia in Child < 6 years

Organism Penicillins Cephalosporins Aminoglycoside

Other

MSSA Nafcillin 1˚, 2˚, 3˚ except Ceftaz

--- ClindamycinLinezolidVancomycin

MRSA --- --- --- BactrimClindamycinLinezolidVancomycin

Strep pneumoniae

Penicillin, Ampicillin,Nafcillin

1˚, 2˚, 3˚ except Ceftaz

--- LinezolidVancomycinAzithromycin

Group A strep All PCN 1˚, 2˚, 3˚ except Ceftaz

--- ClindamycinLinezolid

H flu type B Ampicillin 2˚, 3˚ except Ceftaz

--- Aztreonam

Case Study

A 10-year-old girl presents with two days of fever, cough, and increased work of breathing. CBC shows a WBC count of 35,000 with 80% PMN’s. CXR shows a segmental infiltrate in the left lower lobe. A blood culture is drawn and the child is admitted.



• Antibiotic regimens if she has anaphylaxis to penicillin?

Antibiogram fro Community Pneumonia in a Child > 6 years

Possible

Cause

Penicillin Cephalo-

sporin

Amino-

glycoside

Other

Strep

pneumoniae

All

even if resist.

1˚, 2˚, 3˚ --- Clinda,Eryth, Azithro

Mycoplasma

pneumoniae

--- --- --- Eryth,

Azithro

Case Study

An 11-day-old female infant presents with temperature to 39.5˚ C rectally, poor feeding, and lethargy. No source for the fever is found on physical exam. Blood culture is drawn. Urinalysis and CXR are normal. CSF shows 400 WBC’s (90% PMN’s), glucose 25/90, protein 175.

• Differential diagnosis?



Antibiogram for Late Onset Neonatal Meningitis

Possible

Cause

Penicillin Cephalo-

sporin

Amino-

glycoside

Other

[St. aureus] Vanco

Listeria Ampicillin or other PCN

Gent, Tobra

as adjunct

---

Group B

strep

Ampicillin or other PCN

1˚, 2˚, 3˚ Gent, Tobra

as adjunct

---

GNR Ampicillin

(only ~50%)

1˚, 2˚, 3˚ Gent, Tobra ---

Antibiotics II Glycopeptides Aminoglycosides Macrolides “The Mycins”

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Transcript of Antibiotics II Glycopeptides Aminoglycosides Macrolides “The Mycins”