antibiotics ii glycopeptides aminoglycosides macrolides “the mycins”
DESCRIPTION
Antibiotics II Glycopeptides Aminoglycosides Macrolides “The Mycins”. Margaret K. Hostetter, M.D. Vancomycin +. GRAM POSITIVES GRAM NEGATIVES ANAEROBES. Enterococcus. Meningococcus. Enterobacter. Pneumo. Grp B strep. Grp A strep. Klebsiella. St. aureus. Pseud spp. Serratia. Ps.aerug. - PowerPoint PPT PresentationTRANSCRIPT
Antibiotics II
GlycopeptidesAminoglycosides
Macrolides“The Mycins”
Margaret K. Hostetter, M.D.
St.
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GRAM POSITIVES GRAM NEGATIVES ANAEROBES
THE GLYCOPEPTIDES
Vancomycin +
+ requires addition of an aminoglycoside
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GRAM POSITIVES GRAM NEGATIVES ANAEROBES
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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GRAM POSITIVES GRAM NEGATIVES ANAEROBES
+
+ - requires addition of a peniclllin
+Tobramycin
Amikacin
Gentamicin
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GRAM POSITIVES GRAM NEGATIVES ANAEROBES
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.
• Possible causative organisms?
• Antibiotic regimens?
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
St.
epi
St.
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GRAM POSITIVES GRAM NEGATIVES ANAEROBES
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.
• Possible causative organisms?
• Antibiotic regimens?
• 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.
• Possible causative organisms?
• Antibiotic regimens?
• 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?
• Possible causative organisms?
• Antibiotic regimens?
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 ---