Transcript Antibiotic_intern_lecture

Empiric Antibiotic Therapy
Antibiotics
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The appropriate use of empiric antibiotics is central to medical practice.
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The goals of empiric antibiotic regimens are:
– To provide adequately broad coverage to treat an infection before the culprit
organism is identified.
– To use a sufficiently narrow spectrum of coverage so that antibiotic resistance
and adverse drug reactions are minimized.
– Review previous cultures and sensitivities
– Always remember, the cornerstone of effective infectious treatment is good
source control. -David Butler, MD, Infectious Disease UCSD
Antibiotics
• Today we will discuss:
– Specific regimens by organ system
– Organisms to be worried about
Major infections in internal medicine
• Pneumonia
• Meningitis and encephalitis
• Urinary tract infections
• Cellulitis and other soft tissue infections
• Fever in the neutropenic patient
“The captain of the men of death”
• Pneumonia is the sixth-leading
cause of death in the US
• 4,000,000 cases/year in
ambulatory patients
• More than 600,000
admissions/year
– ~14% mortality among inpatients
– Likely higher in elderly inpatients
Common organisms
• Streptococcus pneumoniae – most commonly identified cause of
pneumonia across the board.
• Haemophilus influenzae and parainfluenzae – second most common
organisms in some studies; more common in smokers.
• Mycoplasma pneumoniae and Chlamydophila pneumoniae– frequent
pathogens among otherwise healthy people, often present atypically.
• Legionella pneumophila – also considered an “atypical” organism, may be
transmitted via fomites.
• Moraxella, Streptococcus pyogenes (GAS).
Other organisms
• Pseudomonas aeruginosa
• Coccidioides immitis
• Staphylococcus aureus
• Klebsiella pneumoniae, E. coli, other GNRs
• Mycobacterium tuberculosis
• Pneumocystis jiroveci
• Anaerobes: Bacteroides, Peptostreptococcus
• Viruses
Pneumonia: Guidelines
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ATS and IDSA guidelines for
pneumonia recommend initial
empiric therapy based on patient
status and risk factors.
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Patient categories based on clinical
status, comorbidities, and risks for
infection with:
– penicillin- and multidrug-resistant
pneumococci (MDRSP)
– enteric Gram-negative organisms
– Pseudomonas aeruginosa
Pneumonia: some random thoughts
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Antibiotics within 4-8 hours
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If someone is sick enough to be admitted, start with two drugs.
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Use intravenous therapy up front.
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Always get blood cultures beforehand.
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Consider sputum cultures if feasible.
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Remember the “red flags”:
– Multilobar disease, effusions, upper lobe disease, mediastinal
lymphadenopathy, cavitary lesions.
– Again don’t write pneumonia and effusion in the same note without a tap
procedure note soon to follow
Community-acquired pneumonia:
regimens
• Ceftriaxone and azithromycin
– Ceftriaxone: 3rd generation cephalosporin (β-lactam)
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Good coverage of S. pneumoniae, H. influenza, Moraxella.
Use higher doses in patients <50 years old: 2 g IV q24h.
Allergic reactions in PCN-allergic patients rare (3-5 %).
“Fun-fact” reaction: biliary sludging.
– Azithromycin: macrolide
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Covers the “atypicals”: Mycoplasma, Chlamydophila, Legionella
Reasonable pneumococcus coverage but resistance increasing.
Less GI upset than erythromycin.
Probably not suitable as outpatient monotherapy in San Diego.
Respiratory Fluoroquinolones
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Moxifloxacin, Levofloxacin, and gatifloxacin
(off the market).
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Inhibitors of DNA gyrase.
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Broad coverage of pneumococcus, Gramnegatives, atypicals.
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Limited activity against Pseudomonas,
Staphylococcus.
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Ciprofloxacin has limited Gram-positive
coverage but is better for Pseudomonas.
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No anaerobic coverage.
Fluoroquinolones
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Moxifloxacin and Levofloxacin are good monotherapy choices for CAP patients who
can be treated as outpatients.
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Moxifloxacin (Avelox) is the quinolone of choice at NMCSD
– Do not have to dose based on renal function
– DOES NOT cover UTI
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Consider using with ceftriaxone for initial inpatient therapy.
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Overuse is breeding resistance.
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Adverse reactions of note:
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QT prolongation (may be more of a concern with moxifloxacin).
Achilles tendon rupture (cipro)
Hypo/hyperglycemia, especially with gatifloxacin (which is why it’s off the market).
Relatively contraindicated in children.
Pneumonia: additional considerations
• Consider aspiration risk in patients with alcohol/drug abuse, dementia,
stroke.
– Cover anaerobes with piperacillin/tazobactam.
• Piperacillin/tazobactam (Zosyn™)
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Anti-pseudomonal penicillin with β-lactamase inhibitor.
Broad coverage (Gram-positive, Gram-negative, anaerobes).
Moderate but less-than-fantastic staphylococcal coverage.
Indicated in hospital-acquired pneumonias:
• Usual dose 3.375 g IV q6h, but 4.5 g IV q6h if concerned for
Pseudomonas.
• High sodium load (over 2 grams/day at usual doses).
• Combine with moxifloxacin or levofloxacin for atypical coverage,
ciprofloxacin or aminoglycosides for Pseudomonas.
Pneumonia: additional considerations
• Why don’t patients get better?
– Nosocomial infections with MSSA, MRSA (50% of all S. aureus)
– Complicated pleural space
– Fungal infections (esp. coccidioidomycosis)
– Tuberculosis
– Other infections
– Consider PCP in the immunosuppressed or with HIV risk factors
Pneumonia summary
• Community-acquired
– Ceftriaxone 1-2 g IV q24h
PLUS
– Azithromycin 500 mg IV/PO
q24h
– Moxifloxacin 400 mg IV/PO
q24h
– Levofloxacin 750 mg IV/PO
q24h
• Hospital-acquired
– Pip/Tazo 3.375-4.5 g IV q6h
– +/- Vancomycin or Linezolid
for MRSA coverage
• Anaerobes
– Pip/Tazo 3.375g IV q6h
Meningitis and encephalitis
• CNS infections are common
admitting diagnoses.
• Common organisms:
– Enteroviruses, HSV, maybe
arboviruses?
– Streptococcus pneumoniae,
Neisseria meningitidis,
Haemophilus influenzae (rarer)
– Mycobacteria, Coccidioides,
Cryptococcus in special situations.
CSF evaluation
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If possible, perform LP on side and
get opening pressure especially if
considering fungal or MTB
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Cell count with differential – tube 1
and 4
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Protein, glucose
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Gram stain and culture
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Enterovirus and HSV PCR – ensure
the ER sent it (makes you feel warm
and fuzzy if you don’t think it’s
bacterial)
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Consider AFB and fungal cultures,
cocci serology, crypto antigen if
indicated.
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Save extra CSF and hand-deliver
samples to the lab.
• For God’s sake, save extra CSF
and hand-deliver samples to the
lab.
Empiric treatment of meningitis
• Generally healthy adults:
– Ceftriaxone 2 g IV q12h
– Vancomycin 15 mg/kg IV q12h, could talk to pharmacy about q8 hour dosing if
young healthy patient (Troughs 15-20)
• For coverage of MDRSP until cultures available or negative.
• Probably does not cause renal impairment alone.
– Consider dexamethasone 0.15mg/kg IV q6h with first dose for confirmed or
highly-suspected bacterial meningitis continue for 48-96 hours.
• If patients are elderly, immunosuppressed, pregnant, or alcoholic, add
ampicillin 2 g IV q4h for coverage of Listeria monocytogenes.
• If encephalitis is a concern, add HSV coverage with acyclovir 10 mg/kg IV
q8h.
– Remember to maintain adequate urine output (15cc/kg/day).
Extra thoughts on meningitis
• In patients with more insidious presentations and markedly elevated CSF
protein, consider:
– Coccidioidal meningitis
• Lymphocytic pleocytosis in the CSF with elevated protein.
• Initial treatment with at least fluconazole 800 mg PO q24h – lifelong therapy
indicated if diagnosis confirmed.
– Cryptococcal meningitis
• Always high on the differential in HIV.
• India ink stain good for quick diagnosis although CSF antigen is probably a better
test.
• Treated with ampho B and flucytosine initially.
– Tuberculous meningitis
• Especially in subacute patients with appropriate travel/exposure history.
• Probably should be talking with ID if you’ve reached this point.
Neurological infections summary
• Start with ceftriaxone 2 g IV q12h and vancomycin 15 mg/kg IV q12h.
• Add ampicillin 2 g IV q4h if immunosuppressed, >50 years, or alcoholic.
• Acyclovir 10 mg/kg IV q8h if encephalitic.
• Fluconazole 800 mg PO q24h (at least) if cocci is a major concern.
– Remember LFT monitoring when using azoles.
Pyelonephritis
• Clinically presents with CVA
tenderness, fever, and pyuria in
most patients.
– May be more subtle in the
elderly and immunosuppressed.
• Urinalysis and culture are
mandatory and should be
obtained prior to antibiotics in
the hospitalized patient.
• Common organisms:
– Escherichia coli
– Other GNRs: Proteus,
Enterobacter, Klebsiella,
Providencia
– Enterococcus faecalis and
faecium
Urine Gram stain
• For some mysterious reason, urine is the one body fluid not routinely
stained by the lab.
– Call 2-9234 and ask for a Gram stain.
• Gram-negative rods
– E. coli, other Enterobacteriaciae.
– Start with a quinolone (cipro, levo) – moxi not effective.
– Alternatives: ceftriaxone 1-2 g IV q24h, gentamicin 5 mg/kg IV q24h.
• Gram-positive cocci
– Group B strep, Enterococcus, Staphylococcus saprophyticus.
– Treat with ampicillin 2 g IV q4h once confirmed -> might start with vancomycin
empirically.
– Consider vancomycin in patients with Foleys or recent hospitaliztion.
– Note that E. faecium=VRE (approx 10%) -> rare at NMCSD.
– S. aureus in the urine = bacteremia/endocarditis until proven otherwise.
Complicated UTIs
• Persistent fever on appropriate antibiotics for 72 hours: obtain renal
ultrasound to rule out perinephric abscess.
• Renal obstruction, renal transplant, indwelling catheters:
– Consider additional coverage for Pseudomonas, Enterobacter, Acinetobacter.
– Pip/tazo may be appropriate for broader coverage
• Candiduria may be treated with short courses of oral fluconazole.
– I don’t generally advocate treating candiduria in an asymptomatic patient, but
treatment may be warranted if the patient is febrile or otherwise symptomatic
with pyuria on UA.
• E. faecium may represent VRE – this would be treated with linezolid 600 mg
PO/IV q12h, but don’t treat all enterococci empirically as though they’re VRE.
– Nausea, diarrhea, and thrombocytopenia are all common side effects of linezolid.
Pyelonephritis summary
• E. coli and other GNRs are most common and respond well to quinolones
in general.
• Suspect Enterococcus if GPCs are found on Gram stain.
– Vancomycin 15 mg/kg IV q12h or ampicillin 2 g IV q4h (if sensitive).
– Consider vancomycin in the recently hospitalized
– E. faecium may be VRE – would treat with linezolid or daptomycin in most
cases.
• Consider Pip/tazo in complicated UTIs.
– Pip/tazo will cover E. faecalis (if sensitive).
• 14 days of total therapy is generally recommended, especially in β-lactambased regimens.
Cellulitis and soft-tissue infections
• Staphylococcus aureus and Streptococcus pyogenes (group A β hemolytic
streptococci - GABHS).
– GABHS tends to evolve more rapidly and may have regional lymphadenopathy
and lymphatic streaking on exam.
• Admissions usually for failure of outpatient treatment.
– Think MRSA, especially in patients from MCRD and NSWC.
• Initial regimens:
– Vancomycin 15 mg/kg g IV q12h
– If MSSA or streptococci are confirmed:
• Nafcillin or oxacillin 2 g IV q4h
• Cefazolin 1 g IV q8h
• Clindamycin 900 mg IV q8h
Special considerations
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Necrotizing fasciitis
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Consider when pain is intense or rapidly progressive.
Early surgical consultation and debridement.
Antibiotics are only an adjunct to surgery:
• Clindamycin 900 mg IV q8h
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• Unasyn 3 g IV q6h OR Pip/Tazo 3.375 g IV q6h
AND
• Vancomycin 15 mg/kg IV q12h (dose for troughs 15-20).
Diabetic foot infections
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Generally polymicrobial (GPCs, GNRs, anaerobes).
Empiric coverage:
• Pip/Tazo 3.375 g IV q6h
• Clindamycin 900 mg IV q8h and ciprofloxacin 400 mg IV q12h
• Concider Augmentin as outpt therapy with close follow-up
Duration of therapy depends on tissue viability and the presence/absence of osteomyelitis.
Fever in neutropenia
• Temperature ≥38.3C x 1 or ≥38.0C for > 1 hour
• Absolute neutrophil count <500 (or <1000 and expected to be less than
500 in the next 24 hours)
– Total WBCs x (% PMNs + % bands)
• Numerous causes, specific etiology may not be isolated.
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Pneumonia: pneumococcus, Klebsiella, E. coli, Pseudomonas.
Urinary tract: E. coli, Proteus, Klebsiella, Enterococcus
Mucositis: S. viridans
Indwelling catheters: S. aureus, coagulase-negative staphylococci, Candida.
Viruses, invasive fungal pathogens, non-infectious sources of fever.
Initial empiric management
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Thorough history and physical exam, including oral cavity, indwelling lines, perirectal region.
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Blood and urine cultures, chest radiograph, sputum if available.
– Separate cultures from catheter sites.
– Fungal isolators.
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Initial antibiotics:
– Pip/Tazo 4.5 g IV q6h and tobramycin 5mg/kg IV q24
– Cefepime 2 g IV q8h
– Aztreonam 2 g IV q6-8h and vancomycin 1-1.5 g IV q12h if PCN-allergic.
– Add vancomycin to patients if suspicious of Gram-positive UTIs, catheter infections,
mucositis, or prior MRSA infections.
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Other regimens (e.g., Pip/Tazo alone, meropenem alone) appear effective; institutions will
vary in their “routine” regimen.
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Don’t forget aggressive fluid resuscitation in the septic patient.
Additional notes
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Consider adding metronidazole 500 mg IV q6h if highly suspicious of an anaerobic
infection OR if C. difficile is a concern (oral metronidazole preferable for C.
difficile).
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Empiric antivirals generally not indicated, but acyclovir 10 mg/kg IV q8h
appropriate if vesicular or ulcerated lesions are noted on exam.
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If no improvement after 3-5 days of broad-spectrum antibiotics, add antifungals.
– Traditional drug of choice: amphotericin B
– Today, typically we use caspofungin or voriconazole.
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Removal of indwelling catheters mandatory if patient is septic or if S. aureus is
isolated from the blood.
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Consider echocardiography if bacteremic with a new murmur.
Final comments
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Get cultures before antibiotics whenever possible.
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Review CHCS frequently for results or check out the lab personally.
Remember to adjust dosing for renal insufficiency.
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MDRD algorithm – www.nephron.com
Check Sanford for dosage adjustments.
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Be familiar with common adverse reactions.
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If you’re thinking about using the exotic drugs, you might want to think about consulting ID.
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Be aware of the FORBIDDEN LIST OF ANTIBIOTICS THAT REQUIRE I.D.
APPROVAL.
– Meropenem, Imipenem, Ertapenem, Linezolid, Daptomycin, Synercid, Colistin,
Tigecycline
Questions