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Empiric Antibiotic Therapy. Antibiotics. The appropriate use of empiric antibiotics is central to medical practice. The goals of empiric antibiotic regimens are: To provide adequately broad coverage to treat an infection before the culprit organism is identified.

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Antibiotics
Antibiotics

  • The appropriate use of empiric antibiotics is central to medical practice.

  • 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


Antibiotics1
Antibiotics

  • Today we will discuss:

    • Specific regimens by organ system

    • Organisms to be worried about


Major infections in internal medicine
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
“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
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
Other organisms

  • Pseudomonas aeruginosa

  • Coccidioides immitis

  • Staphylococcus aureus

  • Klebsiella pneumoniae, E. coli, other GNRs

  • Mycobacterium tuberculosis

  • Pneumocystis jiroveci

  • Anaerobes: Bacteroides, Peptostreptococcus

  • Viruses


Pneumonia guidelines
Pneumonia: Guidelines

  • ATS and IDSA guidelines for pneumonia recommend initial empiric therapy based on patient status and risk factors.

  • 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
Pneumonia: some random thoughts

  • Antibiotics within 4-8 hours

  • If someone is sick enough to be admitted, start with two drugs.

  • Use intravenous therapy up front.

  • Always get blood cultures beforehand.

  • Consider sputum cultures if feasible.

  • 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
Community-acquired pneumonia: regimens

  • Ceftriaxone and azithromycin

    • Ceftriaxone: 3rd generation cephalosporin (β-lactam)

      • 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

      • 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
Respiratory Fluoroquinolones

  • Moxifloxacin, Levofloxacin, and gatifloxacin (off the market).

  • Inhibitors of DNA gyrase.

  • Broad coverage of pneumococcus, Gram-negatives, atypicals.

  • Limited activity against Pseudomonas, Staphylococcus.

  • Ciprofloxacin has limited Gram-positive coverage but is better for Pseudomonas.

  • No anaerobic coverage.


Fluoroquinolones
Fluoroquinolones

  • Moxifloxacin and Levofloxacin are good monotherapy choices for CAP patients who can be treated as outpatients.

  • Moxifloxacin (Avelox) is the quinolone of choice at NMCSD

    • Do not have to dose based on renal function

    • DOES NOT cover UTI

  • Consider using with ceftriaxone for initial inpatient therapy.

  • Overuse is breeding resistance.

  • Adverse reactions of note:

    • 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
Pneumonia: additional considerations

  • Consider aspiration risk in patients with alcohol/drug abuse, dementia, stroke.

    • Cover anaerobes with piperacillin/tazobactam.

  • Piperacillin/tazobactam (Zosyn™)

    • 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 considerations1
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
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
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
CSF evaluation

  • If possible, perform LP on side and get opening pressure especially if considering fungal or MTB

  • Cell count with differential – tube 1 and 4

  • Protein, glucose

  • Gram stain and culture

  • Enterovirus and HSV PCR – ensure the ER sent it (makes you feel warm and fuzzy if you don’t think it’s bacterial)

  • Consider AFB and fungal cultures, cocci serology, crypto antigen if indicated.

  • 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
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
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
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
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
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
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
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-lactam-based regimens.


Cellulitis and soft tissue infections
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
Special considerations

  • Necrotizing fasciitis

    • 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

        AND

      • 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

    • 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
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.

    • 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
Initial empiric management

  • Thorough history and physical exam, including oral cavity, indwelling lines, perirectal region.

  • Blood and urine cultures, chest radiograph, sputum if available.

    • Separate cultures from catheter sites.

    • Fungal isolators.

  • 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.

  • Other regimens (e.g., Pip/Tazo alone, meropenem alone) appear effective; institutions will vary in their “routine” regimen.

  • Don’t forget aggressive fluid resuscitation in the septic patient.


Additional notes
Additional notes

  • 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).

  • Empiric antivirals generally not indicated, but acyclovir 10 mg/kg IV q8h appropriate if vesicular or ulcerated lesions are noted on exam.

  • 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.

  • Removal of indwelling catheters mandatory if patient is septic or if S. aureus is isolated from the blood.

  • Consider echocardiography if bacteremic with a new murmur.


Final comments
Final comments

  • Get cultures before antibiotics whenever possible.

    • Review CHCS frequently for results or check out the lab personally.

  • Remember to adjust dosing for renal insufficiency.

    • MDRD algorithm – www.nephron.com

    • Check Sanford for dosage adjustments.

  • Be familiar with common adverse reactions.

  • If you’re thinking about using the exotic drugs, you might want to think about consulting ID.

  • Be aware of the FORBIDDEN LIST OF ANTIBIOTICS THAT REQUIRE I.D. APPROVAL.

    • Meropenem, Imipenem, Ertapenem, Linezolid, Daptomycin, Synercid, Colistin, Tigecycline