MEDCH 401 clinical use of beta-lactams
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CLINICAL USE OF BETA-LACTAMS Douglas Black, Pharm.D. Associate Professor School of Pharmacy University of Washington [email protected] WHY IS INFECTIOUS DISEASE PHARMACOTHERAPY SO CONFUSING? • Microbial taxonomy constantly changes • New antimicrobials are continually being developed, although maybe not at the rate we would like • Treatment is straightforward when the pathogen is known, but empiric therapy is difficult • Antibiotic resistance must always be taken into account • There are often many possible treatment choices but usually only one best choice NEW ANTIBACTERIAL AGENTS APPROVED IN THE U.S. (1983-2002)
Transcript of MEDCH 401 clinical use of beta-lactams
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CLINICAL USE OF BETA-LACTAMS
Douglas Black, Pharm.D.Associate ProfessorSchool of Pharmacy
University of [email protected]
WHY IS INFECTIOUS DISEASE PHARMACOTHERAPY SO CONFUSING?
• Microbial taxonomy constantly changes
• New antimicrobials are continually being developed, although maybe not at the rate we would like
• Treatment is straightforward when the pathogen is known, but empiric therapy is difficult
• Antibiotic resistance must always be taken into account
• There are often many possible treatment choices but usually only one best choice
NEW ANTIBACTERIAL AGENTS APPROVED IN THE U.S. (1983-2002)
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MASTERING TREATMENT OF AN INFECTIOUS DISEASE
• Know the most common pathogens in rank order of likelihood or importance
• Know the resistance patterns of the pathogens in question
• Know the drug(s) of choice in a patient with a classic case
• Know the best alternative for a patient unable to receive the drug of choice
• Know the drug of choice in pregnancy
CASE 1. A 5-year-old boy presents with fever, purulent tonsillar exudate, and cervical lymphadenopathy. No rash is evident.
Diagnosis: Tonsillopharyngitis
CASE 1: TONSILLOPHARYNGITIS
• Most likely pathogens:– Virus– Streptococcus pyogenes (also known as
Group A ß-hemolytic Streptococcus or GABS)
– Arcanobacterium haemolyticum (rare)
• Drug of choice– Penicillin VK (won’t cover A. haemolyticum)
• PEARL: Penicillin-resistant S. pyogenes has never been reported
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CASE 2. A 20-month-old girl comes to the clinic with a cough and runny nose. She is very fussy and continually tugs at her left ear. Her temperature is 102 F, her left ear drum is red and immobile, and bony landmarks are not visible.
Diagnosis: Acute otitis media
Most likely pathogens: Streptococcus pneumoniae, Hemophilus influenzae, Moraxella catarrhalis
Global Susceptibility ofGlobal Susceptibility ofS. pneumoniaeS. pneumoniae:: 20012001--20022002
No. ofNo. of Percent SusceptiblePercent SusceptibleCountryCountry IsolatesIsolates PenicillinPenicillin AzithromycinAzithromycin LevofloxacinLevofloxacin
ASIAASIASouth KoreaSouth Korea 283283 2424 1818 9797ThailandThailand 168168 2929 4545 9999Hong KongHong Kong 188188 3131 2323 92 (98 in 2003)92 (98 in 2003)JapanJapanaa 218218 4646 3232 9999ChinaChina 180180 8383 1818 9898EUROPEEUROPEFranceFrance 760760 4747 4545 9999SpainSpain 649649 4949 6060 9999ItalyItaly 813813 8282 6969 9999UKUK 505505 9292 8787 100100GermanyGermany 1,1881,188 9595 8585 100100
a: Japan data (1998) from Sahm, et al. JAC, 2000;45:457-466. Data on file, Ortho-McNeil Pharmaceutical, Inc.
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CASE 2: ACUTE OTITIS MEDIA
• Most likely pathogens:– Streptococcus pneumoniae– Hemophilus influenzae– Moraxella catarrhalis
• Drug of choice– Amoxicillin (90 mg/kg/day, divided
bid)
• PEARL: amoxicillin/clavulanate is not considered a better initial choice
CASE 3. Same 20-month-old girl, 48 hours later, no improvement.
Diagnosis: Refractory acute otitismedia
CASE 3: REFRACTORY AOM
• Most likely pathogens:– Hemophilus influenzae– Moraxella catarrhalis– Could be something unusual
• Drug of choice– Amoxicillin/clavulanate (Augmentin)
• PEARL: cefdinir is the best-tastingliquid cephalosporin
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CASE 4. A 46-year-old male complains of headache and facial pain aggravated by stooping, and continuous nasal discharge. He says he caught a cold ten days ago and has had symptoms ever since. Decongestants provide little relief.
Diagnosis: Acute bacterial sinusitis
THE PARANASAL SINUSES
(The sphenoid sinuses are between the eyes and located posteriorly)
CASE 4: ACUTE BACTERIAL SINUSITIS
• Most likely pathogens:– Streptococcus pneumoniae– Hemophilus influenzae– Moraxella catarrhalis
• Drug of choice– Amoxicillin
• PEARL: Some otolaryngologists prefer amoxicillin/clavulanate for initial therapy
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CASE 5. A 35-year-old construction worker complains of a tender and swollen right arm. The arm is erythematous and warm to the touch.
Diagnosis: Cellulitis
Most likely pathogens: Staphylococcus aureus, Streptococcus pyogenes
Complicating issue: the possibility of CA-MRSA
CELLULITIS
ERYSIPELAS
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IMPORTANT MILESTONES IN THE HISTORY OF RESISTANT
STAPHYLOCOCCUS AUREUS
Treatment approach still not defined1999“Clinical” emergence of
CA-MRSA
Vancomycin approved in 19581996Emergence of VISA
(GISA)
Reported 3 times so far2002Emergence of VRSA
Methicillin approved in 19611961Emergence of MRSA
Penicillin introduced into clinical practice in
19421942
Penicillinase-producing S. aureus appears in an Oxfordshire constable
COMMENTYEAREVENT
20.3
43.3
05
101520253035404550
MSSA MRSA
Mor
talit
y, %
Overall risk = 2.97 (95% CI: 1.12 - 7.88)*
IMPACT OF MRSA ON BACTEREMIA
P = .03
Methicillin resistance is an independent predictor for shock and risk factor for death in S aureus bacteremia†
MRSA is also associated with increased length of stay and higher hospital costs, although data are conflicting (Engemann et al, CID 2003; 36: 592)
*Talon D, et al. Eur J Intern Med. 2002; †Soriano A, et al. Clin Infect Dis. 2000.
S aureus bacteremia: mortality
CASE 5: CELLULITIS
• Most likely pathogens:– Staphylococcus aureus– Streptococcus pyogenes
• Drug of choice (if using oral therapy)– Dicloxacillin or cephalexin
• Drug of choice (if using IV therapy)– Nafcillin or cefazolin
• PEARL: the choice depends in part on the patient
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CASE 6. A 67-year-old man is seen by his physician for fever, chills, malaise, and night sweats. A new heart murmur is audible. The man mentions a visit to the dentist a month ago. He has poor dentition.
Diagnosis: Acute bacterial endocarditis
A GOOD EXAMPLE OF POOR DENTITION
CASE 6: ENDOCARDITIS
• Most likely pathogens:– Viridans group Streptococcus– Fastidious Gram-negative bacillus
(part of oral flora)
• Drug of choice– Penicillin G (± gentamicin)– Ceftriaxone
• PEARL: oral beta-lactams should never be used for endocarditis
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CASE 7. A 24-year-old woman develops fever, chills, flank pain, abdominal pain, nausea, and vomiting. She is barely able to get out of bed. She is flushed and diaphoretic.
Diagnosis: acute pyelonephritis
Most likely pathogens: E. coli, maybe another enteric Gram-negative bacillus
AUGUST 2003 NNIS REPORT for the period 1/98-6/03
6.1
1.3
5.5
20.3
8.5
12.4
27.2
11.5
42.0
Non-ICU (%)
2.76.2Fluoroquinolone-resistant E. coli
0.41.23rd-gen ceph resistant E. coli
1.85.83rd-gen ceph resistant Klebsiella
9.626.63rd-gen ceph resistant Enterobacter
4.713.8Ceftazidime-resistant P. aeruginosa
7.519.4Imipenem-resistant P. aeruginosa
23.135.8Ciprofloxacin-resistant P. aeruginosa
4.612.7Vancomycin-resistant Enterococcus
25.951.6Methicillin-resistant S. aureus
Outptareas (%)
ICU (%)ORGANISM
NNIS. Am J Infect Control 2003; 31: 481-98
CASE 7: PYELONEPHRITIS
• Most likely pathogens:– E. coli– Maybe another enteric Gram-negative
bacillus, e.g. P. mirabilis
• Drug of choice– Ceftriaxone– Levofloxacin is cheaper
• PEARL: pyelonephritis (upper UTI) is much different than cystitis (lower UTI), despite the pathogens being the same
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CASE 8. A 56-year-old intubatedpatient in the ICU recovering from heart surgery spikes to 39.9 C. His WBC is 25,900 with a neutrophil predominance and he has impressive infiltrates on chest x-ray. Sputum Gram stain reveals 4+ WBC, 4+ GNR, 2+ GPC.
Diagnosis: Hospital-acquired pneumonia
A NORMAL CHEST X-RAY
PULMONARY INFILTRATES
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CASE 8: HOSPITAL-ACQUIRED PNEUMONIA
• Most likely pathogens:– Enteric Gram-negative bacilli, especially
resistant strains– Pseudomonas aeruginosa– Staphylococcus aureus, possibly MRSA
• Drug of choice– Imipenem/cilastatin or meropenem– Vancomycin might be added
• PEARL: The offending organism will be conclusively identified <50% of the time
CASE 9. A 55-year-old diabetic male complains of fevers to 38.3, worsening erythema, and purulent drainage from a chronic foot ulcer. His WBC is 14,800 with 83% neutrophils. ESR (erythrocyte sedimentation rate) is 76 mm/hr.
Diagnosis: Diabetic foot ulcer, possible osteomyelitis
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CASE 9: DIABETIC FOOT
• Most likely pathogens:– Just about anything: Gram-negative
bacilli including Pseudomonas, Gram-positive cocci, anaerobes
• Drug of choice– Piperacillin/tazobactam– Ticarcillin/clavulanate
• PEARL: not all infections are approached with curative intent
