Infectious Disease Intern Lecture

2014-15

Empiric Antibiotic TherapyTreating proven or suspected infection at a time when the

pathogen is unknownAppropriate in the following situations

Acute illness very likely to be caused by infection, use of the agent will have significant clinical effect, and delaying therapy might be harmful to the patient (e.g. meningitis, pneumonia, cellulitis, pyelonephritis)

Illness could be due to infection, but the patient is critically ill and therefore withholding antibiotics is risky (e.g. shock, fever/rash)

Fever and neutropeniaChronic or subacute illness that is almost certainly due

to infection, but microbiological confirmation will not be available for days or weeks and delaying therapy might be harmful to the patient or others (e.g. TB, AIDS histo)

Empiric Antibiotic TherapyGeneral RulesHave a lower threshold to begin empiric therapy in

the patient whose systemic or local defenses are impaired

Not every patient with fever needs antibioticsConsult your hospital’s antibiogramWhenever possible and as long as the delay will not

be harmful, obtain appropriate specimens for microbiology before beginning therapy (this includes 2 sets of blood cultures for most patients admitted to the hospital with presumed infection- pneumonia, cellulitis, pyelonephritis, etc.)

Change to specific therapy as soon as you have enough information to safely do so

http://connect.uams.edu/clinical/stewardship/

How to Select the Correct Antibiotic(s) What pathogen(s) is (are) likely?

What is the clinical syndrome? What is the patient’s immune status / underlying condition?

Antibody Asplenia Cell-mediated (AIDS, transplantation) PMNs Local factors

Where was the infection acquired? Are there epidemiologic considerations? Do simple tests provide any clues? Are there past studies that might be helpful?

What drug is likely to be effective at the site of infection against the most likely pathogen(s)? Give antibiotics that will penetrate and achieve adequate concentrations at the site of

infection For meningitis the issue is relative penetration into CSF in the presence of meningeal

inflammation For UTI, does the antibiotic get into the urinary tract?

Other considerations Allergy Toxicity profiles Drug interactions Cost Need for intravenous vs. oral

Fever, Shock, and Rash63 yo man with fever, lethargy, and

hypotension admitted to the MICUConjunctival and cutaneous petechiaeDark macules on soles of feetIVDU- needle tracks right armLives in the country and it’s summer

Mylonakis, E. et al. N Engl J Med 2001;345:1318-1330

Should antibiotics be given and if so, which one(s)?Bugs Drugs

Should antibiotics be given and if so, which one(s)?Bugs

S. aureus

DrugsVancomycin


S. aureusS. pneumoniaeOther strepN. meningitidesGNB (maybe)

DrugsVancomycin

Ceftriaxone


S. aureusS. pneumoniaeOther strepN. meningitidisGNB (maybe)R. rickettsii

DrugsVancomycin

Ceftriaxone

Doxycycline

Management of S. aureus BacteremiaNEVER attribute a positive blood culture for S. aureus to

“contamination”*Remove or drain primary focus if one is present, including

iv catheters* Intravenous antibiotics (start with vancomycin)

Nafcillin (or cefazolin) for meth-susceptible (MSSA) Usually vancomycin for methicillin resistant (MRSA) or MSSA

if severely allergic to β- lactams Others

Daptomycin- a lipopeptide that has activity against a broad range of gram positive cocci

Linezolid- an oxazolidinoneDuration

Minimum duration of intravenous therapy for uncomplicated S. aureus bacteremia is 2 weeks from the first day of negative cultures*

4 – 6 weeks for complicated (must decide whether infective endocarditis or not)

Follow-up blood cultures during and after therapy*

* Also True for Candida

Methicillin ResistanceDue to the presence of mec A gene:

encodes penicillin-binding protein 2a (PBP2a)carried on the staphylococcal cassette

chromosome (SCC) mec mobile element (types I-IV)

Confers resistance to ALL penicillins (including those combined with B- lactamase inhibitors), ALL carbapenems, and almost all cephalosporins (except ceftaroline)

Intravenous Antimicrobials for MRSAVancomycin

Tried and True, the “gold standard”Linezolid (Zyvox)

Watch out for bone marrow toxicityDaptomycin (Cubicin)

Not for use in airway-acquired pneumoniaQuinupristin/Dalfopristin (Synercid)

Phlebitis and myopathyTigecycline (Tygacil)

Very broad spectrum, very short serum T1/2Ceftaroline (Teflaro)

Data for SSSIs and CAP

Dosing VancomycinFor septic patients, give loading dose of 20 mg/kgUsual dose after loading is 15 mg/kg (about 1000 mg for

a 70 kg patient)Renal function determines the dosing intervalCheck a trough 30 minutes before the 4th dose

Goal 15-20If it is too low, give drug more frequentlyIf it is too high, give drug less frequently

No need to check a peak levelFor patients with worsening renal function or very low

GFRs, we check a “random” level each morning and give dose if level is <20

Diabetic Foot Ulcer33 yo man admitted with 5 day h/o fever to

103 and swollen footIDDM for 13 years, poor controlRed streaks up medial portion of right leg

with 3 X 4 cm ulcer on heelCopious, foul-smelling pusSensory deficits c/w peripheral neuropathy


S. aureusStreptococci/

EnterococciGram-negative

aerobes (Proteus)Anaerobes

Drugs


S. aureusStreptococci/

EnterococciGram-negative

aerobes (Proteus)Anaerobes

Drugs: Vanco plusPip/tazo or,Imipenem/

ertapenem or, A 3rd gen ceph plus a

drug for anaerobes (Metronidazole or clindamycin) or,

A FQ plus a drug for anaerobes (Metronidazole or clindamycin)

Beta-Lactams

PENICILLINS

Natural penicillinsPenicillinase-resistant

ANTISTAPHYLOCOCCALCarboxy- and ureido-

ANTIPSEUDOMONALAminopenicillins

Pen VPen G

AmpicillinAmoxicillin

Amp/sulbactam

Dicloxacillin NafcillinOxacillin

CarbenicillinTicarcillin

PiperacillinPip/tazobactam

Beta-Lactams

CeftarolineA 5th generation cephalosporinHigh affinity for PBP 2a (MRSA) and to all PBPs

seen in S. pneumoniaeActive against MRSA, ceftriaxone/cefotaxime-

resistant S. pneumoniae and all B-hemolytic streptococci

Also has activity against some gram negatives, but definitely not Pseudomonas

Not active against VREApproved for community-acquired pneumonia

and skin/skin structure infections

Meningitis68 year old asplenic woman with 8 hours of

fever and headacheT 102.8, lethargic, stiff neck,

petechiae/purpuraCSF: 1700 WBC- all PMNs, glucose <10,

protein 150


Neisseria meningitidis

Streptococcus pneumoniae

DrugsCeftriaxone andvancomycin

MeningitisIf neonate or elderly or if cell-mediated

immunity is compromised….

MeningitisADD AMPICILLIN to cover Listeria

monocytogenes

Approach to Initial Management

Uncomplicated Pyelonephritis24 year old woman with fever, chills, flank

pain, nausea/vomitingHad dysuria and frequency for a few days

beforeT 102, right CVA tenderness


Enterobactericeae (most likely E. coli)

DrugsCeftriaxoneImipenem (for

ESBL)

Would not use as empiric therapy anymore: Levofloxacin or ciprofloxacin (NEVER moxifloxacin)

Community-Acquired Pneumonia35 yo man with one day of fever, chills, sharp

chest pain. Cough with sputumExam reveals bronchial breath sounds,

egophony, dullness to percussion at left baseCXR:

What tests are indicated?Pulse oximetryBlood cultures and other tests to try to

identify microbial etiology are not indicated unless you plan to admit the patient

For admitted patients, blood cultures are obtained before the first dose of antibiotics (which should be given within 4-6 hours of arrival to the hospital)

More extensive diagnostic evaluation for patients who are admitted to the MICU

Host Factors Outpatient Inpatient

Medical Ward Intensive Care Unit

No antibiotics within the

past 3 months

Azithromycinor,

Levofloxacin

Ceftriaxone plus azithromycinor,

Levofloxacin alone

Ceftriaxone plus azithromycinor,

Ceftriaxone plus levofloxacinor,

(for severe B-lactam allergy,levofloxacin plus

clindamycin)

AND ADD VANCOMYCIN

Antibiotics for any indication within the

past 3 months*

Levofloxacinor,

Azithromycin plus high dose

amoxicillin ‡or,

Azithromycin plus high dose

amoxicillin-clavulanate §

Suspected aspiration

Amoxicillin-clavulanateor,

Clindamycin

Add clindamycin to one of the above regimensor,

Use piperacillin-tazobactam in place of ceftriaxone in one of the above regimens

*If the recent antibiotic therapy included levofloxacin (or another fluoroquinolone), use one of the azithromycin based regimens. If the recent antibiotic therapy included azithromycin (or another macrolide), use levofloxacin. ‡ Dosage 1 g po tid. §Dosage 2 g po tid

Healthcare- Associated PneumoniaHCAP

Hospital- Acquired PneumoniaHAP

Ventilator- Associated PneumoniaVAP

MicrobiologyAerobic gram negative bacilli

Pseudomonas aeruginosaEscherichia coliKlebsiella pneumoniaeAcinetobacter species

Gram positive cocciStaphylococcus aureus, especially MRSA

Anaerobes are uncommon in VAPLegionella Candida colonizes the airways, but does not

cause pneumonia in immunocompetent hosts

Fever During HospitalizationIf the patient had fever prior to or at the time

of admission,Undiagnosed community-acquired infectionComplication of known community-acquired

infection (e.g. pleural empyema, perinephric abscess)

Failure of community-acquired infection to respond to your therapy

Underlying non-infectious cause

Fever During HospitalizationIf the patient did not have fever prior to or

at the time of admission,Complication of hospitalization

Infectious causes IV catheter-associated Skin- wounds, pressure sores Pneumonia- ventilator-associated UTI- Foley Sinusitis- nasogastric tube C. difficile colitis Cholecystitis, in particular acalculous

Non-infectious causes Medications DVT/pulmonary embolism Atelectasis

Fever During HospitalizationCareful examination

Check all venous and arterial catheter sitesRemove dressings if feasibleTurn the patient over

Virtually all patients will needCXR, CBC, blood and urine cultures

Prevention is the keyCheck i.v. sites daily, remove any unnecessary

devices, get your patients out of bed, avoid over-use of antibiotics

Fever and Tick Exposure46 year old white lady presents with 5 days of

fever, headache, and myalgiaWent camping 10 days agoBP 100/68, HR 110, T 102.4Confused, no rash, neck is suppleLabs: WBC 1,300, platelet 65,000, ALT 130


Ehrlichia chaffeensis

Rickettsia rickettsiiFrancisella

tularensis*

DrugsDoxycycline

Gentamicin

*Does not cause the illness described in the scenario. Tularemia can present as: Ulceroglandular, glandular, oculoglandular, pharyngeal, pneumonic, typhoidal, orsome combination of these.

Tick-Borne Diseases in ArkansasTick exposure in AR is a year-round

phenomenonThe decision to initiate empiric therapy is

based upon the clinical picture; you cannot wait for confirmatory test results

WE DO NOT HAVE LYME DISEASE IN ARKANSAS

HIV Patients Admitted to the Hospital for an AIDS-Related ConditionRepresent a small proportion of the patients we follow in

clinicUsually have an opportunistic infection Most are not taking antiretroviral meds:

Presenting for the first time and will be newly diagnosed with HIV or,

Are known to be HIV positive but haven’t been started on antiretroviral meds yet or,

Are known to be HIV positive but are non-adherent to their prescribed antiretroviral meds

Knowledge of CD4 count is critically important in determining the DDX If there is one from the last couple of months, you do NOT

need to check it againQuantitative HIV RNA (viral load) measurement is NOT

useful in the management of the hospitalized AIDS patient Do NOT order this test on patients known to be HIV positive

Antiretroviral Meds for Hospitalized PatientsNEVER start a patient on antiretrovirals

while (s)he is hospitalized unless an ID consultant advises you to do so

For patients already on meds, continue them in correct doses if they can take PO and if the meds are not causing significant toxicity

For patients already on meds who are too sick to take po meds in the hospital, hold them all

Who ya gonna call?Jon Allen, PA688-9277529-1777

Common Presentations-AIDSCentral Nervous System

Cryptococcal meningitis All patients will have fever and headache Serum crypto antigen is a good screening test Always image brain before performing an LP on

patients who are immunocompromised Always obtain opening pressure when doing an LP

Cerebral toxoplasmosis Focal deficits, seizures, altered mental status Multiple masses on CT/MRI Diagnosis is unlikely if:

Serum toxo IgG is negative Patient is taking TMP/SMX for prophylaxis Solitary mass on MRI

Common Presentations-AIDSFever, night sweats, wasting

DDX Disseminated histoplasmosis Disseminated mycobacterial infection (M. avium,

MTB) Lymphoma

Evaluation CXR, routine blood cultures, serum crypto antigen,

urine histo antigen, blood cultures for mycobacteria and fungus (histo)

Later: bone marrow, CT scan, biopsy…

Common Presentations-AIDSPneumonia

Usual bacteriaMTBPneumocystis jirovecii (PCP)

Usually subacute (sick for a couple of weeks) Fever, non-productive cough, dyspnea, hypoxia CXR can look like anything except effusions and

lymphadenopathy Serum LDH is always high β-glucan will be positive most of the time Begin empiric therapy (high dose TMP/SMX +/-

steroids) AND consult Pulmonary early for BAL

Infectious Disease Intern Lecture

Health & Medicine

Transcript of Infectious Disease Intern Lecture