Infectious Disease

Key Concepts of Anti-Microbial Therapy
Pharmacokinetics: relates to the absorption, distribution, and elimination of a drug.
Absorption: important for determining IV vs PO as well as drug-drug interactions (i.e. PPI + iron)
Distribution: important to note drugs which are lipophilic, protein bound and site of infections (i.e. in poorly vascularized sites).
Elimination: important to adjust for renal or hepatic insufficiency.
Pharmacodynamics: describes the relationship between the drug and its intended antimicrobial effect.
Synergy: when two antibiotics used together have bactericidal activity greater than the sum of the two used alone.
Antagonism is the opposite, use of a second agent decreases the efficacy of the either used individually.
Post-antibiotic effect: the continued bactericidal activity of an antibiotic after the serum levels have fallen below the MIC.
Time-dependent killing: an antibiotic is effective for as long as its serum concentration is above the MIC, concentration-independent.
Examples: b-lactams, glycopeptides (Vancomycin), macrolides, clindamycin.
This is the rationale for continuous infusion therapy. Aim >40% time greater than the MIC.
Concentration-dependent killing: An antibiotic's effectiveness is proportional to the degree which its serum concentration exceeds its MIC.
Examples: aminoglycosides, fluoroquinolones, metronidazole.
This is the rationale for once-daily dosing of aminoglycosides and increased doses of fluoroquinolones.

Therapeutic drug monitoring
Vancomycin
Dosed based on weight, aim 10-15mg/kg (not everyone gets 1 gram)
Monitor serum trough for long-term treatment and in patients with varying renal function or on HD
Aim for trough 2-4x MIC (5-10), but for some infections (i.e. deep tissue infections, endocarditis) may want higher (15-20)
If trough is out of desired range, change INTERVAL of dosing
No need to monitor peak levels
Aminoglycosides
Required for prolonged AG therapy as adverse effects (renal and ototoxicity) are related to drug levels

DOSE is determined based on weight

INTERVAL is determined by drug levels
When using traditional dosing (every 8 hours):
Peak: to check for efficacy, if out of range change DOSE
Trough: to check for safety, if out of range change INTERVAL
When using once-daily dosing:
Obtain an extended interval level (6-14 hours after dose) and then use normogram to determine proper INTERVAL of dosing. Can call pharmacy for help.

Fever
Definition
Average normal oral body temperature is 36.8^oC (normal range 36.4-37.2)
Rectal temps are 0.5^oC degrees higher, axillary temps are lower
Elderly patients have a lower mean body temperature and they may not mount a fever when septic and can even be hypothermic
Work-up when T >= 38.3^oC or one hour of T >= 38.0^oC
If immunosuppressed, concern when >= 38.0^oC (see neutropenic fever)
Evaluation (when called evaluate patient immediately)
Review patient's medical problems
Obtain vital signs and mental status (tachycardic? tachypneic? hypotensive?)
Focus on specific complaints: cough, SOB, N/V/D, urinary symptoms, erythematous IV or CVC line site?
Has patient had fever work-up in the last 48 hours?
Thorough but efficient exam:
Eyeball test
Vital Signs
CVC or other indwelling devices (Foley, drains, etc.)
Often overlooked sites: periodontal, oropharynx (mucositis, parapharyngeal abscess), sinuses, abdomen (abscess), perineum, skin, nails
Differential Diagnosis
Quick:

Wind: Pneumonia, atelectasis, pharyngitis

Water: UTI

Wound: Incisions, cellulitis, skin abscesses

Wires: IV/CVC sites

Wonder drugs: Drug fever

Walk: DVT
Causes of nosocomial infection in the ICU:
Sinusitis (think NGT-related), catheter sepsis, drug fever, wound infection (remember decubital ulcers), pneumonia, pulmonary embolism, acute MI, endocarditis, pericarditis, acalculous cholecystitis, perforated ulcer, pancreatitis, enterocolitis, bowel infarction, urosepsis, DVT, systemic inflammatory response syndrome (SIRS)
Complete differential:
Infections: bacterial, viral, rickettsial, fungal, parasitic
Autoimmune diseases: lupus, polyarteritis nodosa, rheumatic fever, polymyalgia rheumatica, giant cell arteritis, Still's disease, Wegener's granulomatosis, vasculitis, relapsing polychondritis; less prominent in dermatomyositis, adult RA
CNS disease: Cerebral hemorrhage, head injuries, brain and spinal cord tumors, degenerative central nervous system disease (i.e. multiple sclerosis), spinal cord injuries (due to interference with thermal regulatory process rather than "true" fever)
Malignancy (tumor fever)
Hematologic disease: lymphomas, leukemia, hemolytic anemia
Cardiopulmonary/Vascular disease: myocardial infarction, thrombophlebitis, pulmonary embolism, DVT.
Gastrointestinal disease: inflammatory bowel disease, liver abscess, alcoholic hepatitis, granulomatous hepatitis
Endocrine disease: hyperthyroidism, pheochromocytoma may raise temperature due to altered thermal regulation.
Diseases due to chemical agents: drug reactions (including serum sickness), neuroleptic malignant syndrome, malignant hyperthermia or anesthesia, serotonergic syndrome.
Miscellaneous: sarcoidosis, familial Mediterranean fever, tissue injury, postoperative fever, hematoma, febrile transfusion reaction (due to anti-leukocyte antibodies), factitious fever
For persistent or recurrent fevers think secondary infection, resistant bacteria, or abscess
Management
Basic Workup: Blood cultures (bacterial and fungal) from at least 2 sites (peripheral and each lumen on central line), CXR, RUA and Urine culture, sputum/trach culture
For transplant/immunosuppressed patients consider:
Blood: bacterial culture, fungal culture, CMV DNA quant, cocci Ab EIA, aspergillus Ag EIA, crypto Ag, EBV, AFB
Sputum: bacterial culture, fungal culture, Influenza direct Ag A and B, AFB, mycoplasma ab, HSV IgM, RSV Ag, PCP direct stain
Urine: Legionella Ab
Also consider other catheter sites with induration or drainage
LP if CNS infection suspected
If diarrhea present, check C. difficile stool toxin (routine stool cultures are not indicated if diarrhea develops after >48 hours of hospitalization). C. difficile can be associated with markedly elevated WBC.
Consider additional imaging if indicated (i.e. RUQ U/S, sinus CT, LE duplex, abdomen/pelvis CT)
In the absence of an identifiable infection, empiric antibiotic therapy should be used only in those with hypotension/impending septic shock or who are immunocompromised. If clearly infected, hang antibiotics yourself… avoid delay!
Other things to consider:
Fluid replacement if volume depleted.
Removal of heat (i.e. cooling blanket) and antipyretic agents if patient is uncomfortable

Note: do not write antipyretics as a standing PRN so that you can see if an infection is being treated or developing.

Pneumonia
Community acquired Pneumonia in Immunocompetent Hospitalized Patient
Organisms:
S. pneumoniae, H. influenzae, Polymicrobial, Aerobic GNRs, Legionella species, S. aureus, C. pneumoniae, Respiratory viruses
Other agents: M. pneumoniae, M catarrhalis, M. tuberculosis, endemic fungi
Diagnostic Evaluation:
CXR, CBC, Chem7, LFTs, 2 sets of blood cultures; gram stain and sputum culture and pulse oximetry. ABG (if hypoxic)
Consider HIV test (if age<55yo, homeless or other risk factors) (everyone?), urine Legionella Ag (in elderly smoker), AFB stain and culture (if cough>1mo, homeless, other risk factors)
Empiric Therapy:
First antimicrobial dose within 3 hours of initial assessment!
Expanded spectrum fluoroquinolone (levofloxacin) OR 3^rd gen Cephalosporin AND macrolide (azithromycin)

NOTE: This regimen misses MRSA and highly resistant Strep pneumoniae
In severe (ICU) community acquired pneumonia:
Antipseudomonal 4^th generation cephalosporin (cefepime) AND macrolide (azithromycin) OR fluoroquinolone OR other antipseudomonal agent AND aminoglycoside (gentamicin or tobramycin) for first few days
If suspect aspiration:
Ceftriaxone or Levofloxacin
If h/o long term residence facility, need anti-pseudomonal coverage: Levofloxacin or Zosyn or Ceftazidime
If h/o severe periodontal disease, necrotizing PNA on CXR, or EtOH: Add anaerobic coverage: Levofloxacin PLUS (clindamycin OR metronidazole) OR b-lactam with b-lactamase inhibitor
Risk Factors associated with increased morbidity and mortality:
Age > 65
Coexisting illnesses: DM, renal failure, CHF, chronic lung disease, EtOH, aspiration, recent hospitalization, altered mental status
PE: RR>30, BP<90/60, T>=38.3°C, confusion or lethargy
Labs: WBC <4,000 or >30,000, PaO₂<60, PCO₂>50, Cr>1.2, BUN>20, Hct<30, coagulopathy; multilobar disease or effusions on CXR
References:
"Community Acquired Pneumonia in Adults: Guidelines for Management." Clin Infect Dis. 2000;31:347-82.
Mandell LA, Bartlett JG, Dowell SF, et. al. Update of practice guidelines for the management of community-acquired pneumonia in immunocompetent adults. Clin Infect Dis. 2003;37:1405.
Halm EA, Teirstein AS. Clinical practice. Management of community-acquired pneumonia. N Engl J Med. 2002;347:2039.
Marik PE. Aspiration pneumonitis and aspiration pneumonia. N Engl J Med. 2001;344:665.
Hospital acquired Pneumonia
Organisms:
Staph aureus, Strep pneumoniae MRSA, Enteric gram negative rods (Enterobacter species, E. coli, Klebsiella, Proteus species, Serratia marcescens), Haemophilus influenzae, Anaerobes, Pseudomonas aeruginosa, Acinetobacter, Fungi (candida, aspergillus) in neutropenic patients
Diagnostic evaluation:
Suspect in hospitalized patients who have new or progressive lung infiltrates and at least 2 of the following: fever, purulent sputum, leukocytosis
See diagnostic evaluation for CAP
Consider bronchoscopy for bronchoalveolar lavage
Empiric therapy:
Fluoroquinolone + anti-pseudomonal b-lactam (ceftazidime) + vancomycin +/- aminoglycoside
Example: Levofloxacin + piperacillin/tazobactam + vancomycin +/- gentamicin
Consider imipenem after initial double coverage with anti-pseudomonal b-lactam and gentamicin
Add macrolide (IV erythromycin or azithromycin) if Legionella suspected
Add clindamycin if aspiration suspected (controversial)
Add vancomycin if MRSA suspected
Add Amphotericin B in neutropenic patients if high suspicion for fungi (Amphotericin B traditional 1^st line agent.
Consider alternatives such as Itraconazole, Voriconazole, Caspofungin as less side effects (similar efficacy per RCT).
Emerging role for posaconazole (only newer agent with Mucor activity)
References
"Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia." Am J Respir Crit Care Med. 2005;171:388.
Pneumonia in HIV positive patient (see HIV section for more information)
Organisms:
S. pneumoniae, H. influenzae, PCP, M. tuberculosis, Aerobic GNRs (E. coli, Klebsiella), MAI, Fungi (Cryptococcus, Histoplasmosis), CMV, Toxoplasmosis,
Diagnostic evaluation:
See diagnostic evaluation for CAP
Induced sputum for PCP and TB (if negative perform bronchoscopy)
Remember to isolate patient as indicated
Empiric therapy:
Use therapy for CAP AND high-dose trimethoprim/sulfamethoxazole to cover PCP (add prednisone for PaO₂<70) AND high-dose ganciclovir to cover CMV

Tuberculosis
Criteria for a Positive Tuberculin Skin Test

Induration of >= 5 mm
HIV positive
Recent contacts of patients with TB
Fibrotic changes on CXR consistent with prior TB
Organ transplant recipients
Other immunosuppressed patients (those taking the equivalent of >15mg/d of prednisone for 1 month or those taking TNF-a antagonists)

Induration of >= 10 mm
Recent (<5yrs) immigrants from high prevalence countries
Injection drug users
Clinical conditions increasing risk:
DM, CRF, leukemia or lymphoma, head, neck or lung cancers, silicosis, weight loss >= 10% of ideal body weight, gastrectomy or jejunoileal bypass
Residents of and employees of high risk congregate settings:
Prisons, nursing homes, hospitals, homeless shelters
Children <= 4yo or children exposed to adults at high risk
Mycobacteriology laboratory personnel

Induration of >= 15 mm
No risk factors
Active Tuberculosis

Diagnosis
Signs/Symptoms:
Prolonged cough, chest pain, weight loss, fever, chills, night sweats, anorexia, fatigue, sputum production, and hemoptysis
History:
History of TB exposure/infection/disease, past TB treatment, demographic risk factors, medical conditions that increase risk for disease
CXR:
Cannot confirm diagnosis
Abnormalities in apical or posterior segments of upper lobe or superior segment of lower lobe
Appearance may be unusual in HIV patients
Specimen collection:
AFB stain and culture (with susceptibility testing) on induced sputum x 3
Skin testing:
10-25% of people with TB will have a negative skin test
False positives: non-tuberculous mycobacterium, BCG vaccine
False negatives: anergy, recent TB infection, <6 months of age, live virus vaccine, overwhelming disease
QuantiFeron-TB test:
Whole blood test used to detect M. tuberculosis infection

Treatment
Treat based on clinical suspicion! Do not wait for skin test results (can be negative) and culture and susceptibility (may not be available for 3-6 weeks)
Isolation:
Hospitalize very sick patients and those living in congregate or high risk setting; respiratory isolation is recommended for 2 months of treatment until disease is probably not communicable
Empiric Regimens:
4 drugs (isoniazid, rifampin, pyrazinamide, ethambutol OR streptomycin)
Isoniazid 5mg/kg/d (max dose 300mg)
Rifampin 10mg/kg/d (max dose 600mg)
Pyrazinamide 15-20mg/kg/d (max dose 2g)
Ethambutol 25mg/kg/d x 2mos then 15mg/kg/d
Streptomycin 15mg/kg/d IM

Department of Health approval for discharge
72 hours before discharge: call ext 4-0187 (hospital epidemiology) for assistance with DHS discharge care plan
Weekends/holidays: M.D. must call DHS TB physician on call (213)974-1234 to obtain discharge approval
References
David Pegues' Noon conference lecture
Blumberg HM, Burman WJ, et. al. "American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of America: treatment of tuberculosis." Am J Respir Crit Care Med. 2003;167:603.
Targeted Tuberculin Testing and Treatment of Latent Tuberculosis Infection. Am J of Respiratory Critical Care Medicine. 2000;161:S221.

Meningitis
Obtain informed consent from the patient or family member prior to doing lumbar puncture (LP)
Bacterial meningitis is an infectious emergency with a 25% case mortality rate
When acute meningitis is suspected, prompt therapy with antibiotics is the standard of care.
Perform funduscopic exam and consider head CT if you suspect increased intracranial pressure (in patients with coma, papilledema, or focal neurologic findings)
Do NOT perform LP in this setting as herniation may result
If imaging is indicated, obtain blood cultures, institute empiric antibiotic therapy (see below), and THEN obtain CT
Perform LP immediately after the imaging if there is no intracranial mass lesion
Instituting antibiotics 1-2 hours before LP will not decrease diagnostic sensitivity if CSF culture is done in conjunction with blood culture and CSF bacterial antigen testing
Always check the opening pressure (normal < 20cm) unless LP has to be done with patient sitting up.

Cerebral Spinal Fluid Studies
Tube	Amount	Studies
1	1 cc	Cell count and differential
2	1 cc	Glucose and protein
3$	3-5 cc	Gram stain, bacterial culture, fungal culture and stain, AFB culture and smear, India Ink, VDRL, cryptococcal Ag
4	1 cc	Cell count and differential
$If indicated, send for cocci Ab (CF & ID), toxo IgG, HSV PCR, CMV PCR, VZV PCR, TB PCR, lyme, histo Ag, viral culture, bacterial Ag panel, MEM (viral panel) If cancer: cytology If MS: IgG synthesis, oligoclonal bands, myelin basic protein If CNS lupus: antineuronal Ab (75-90% +) and antiribosomal P protein (45-80% +)

CSF Findings in Various Types of Meningitis
Finding	Normal	Bacterial	Viral	TB	Cocci	Cryptococcal
Opening pressure	6-20 cm H2O	inc	nl to mod inc	inc	inc	inc
WBCs & diff	0-5, 85% lymphs	100-1000, PMNs predominate	10-500, lymphs predominate except first few days where PMN's often predominate	25-100, lymphs predominate except early stages where PMN's often predominate	50-1000, initially PMN's predominate then monos, eos occ. present	0-800, lymphs predominate (can be very low or zero in patients with AIDS)
Protein	18-45 mg/dL	100-500, occ > 1000mg/dl	Nl or slightly inc, <100mg/dl	100-200mg/dl	min. inc	20-500mg/dl, avg 100mg/dl
Glucose	45-80 mg/dL or (0.6 x serum glucose)	5-40mg/dl, occ nl	nl	dec	20-40mg/dl, may be nl in early disease	10-40mg/dl
Other	For traumatic LPs, add 1WBC/1000 RBCs	gram stain + in 60%, culture + in 2/3 of cases		AFB smear + in < 25%, culture + in 2/3 of cases after >4 wks	gm stain & culture usually negative	CSF or serum crypto Ag + in 95% of cases, India Ink + in 75%

Empiric Treatment (Adapted from The Sanford Guide to Antimicrobial Therapy, 2006)
Bacterial/CSF Gram stain negative/Immunocompetent patient (note that if Gram stain positive, see specific therapy in Sanford)

Age<50yr
Likely etiology: S. pneumoniae, meningococci, H. influenzae
Treatment: ceftriaxone 2gm IV q12h + dexamethasone 10mg IV q6h x 4d with or just before 1st antibiotic dose + vancomycin 15mg/kg IV q6h
NOTE: IV vancomycin has very poor CNS absorption; if confirmed high level resistant S. pneumoniae, may need to give intrathecal vancomycin which carries risk of seizure.

Age>50yr or other debilitating disease (i.e. alcoholism)
Likely etiology: S. pneumoniae, listeria, Gram-negative bacilli
Treatment: ampicillin 2gm IV q4h + ceftriaxone 2gm Ivq12h + dexamethasone 10 mg/kg q6h IV x 4d with or just before 1st dose of antibiotic (NEJM 347;1549, 1613, 2002;4:139, 2004)

Any age with impaired cellular immunity
Likely etiology: Listeria, Gram-negative bacilli
Treatment: ampicillin 2gm IV q4h + ceftazidime 2gm IV q8h

Post-neurosurgery or head trauma
Likely etiology: S. pneumoniae if CSF leak; S. aureus, coliforms, P. aeruginosa
Treatment: vancomycin (until proven non-MRSA) 500-750gm IV q6h + cefepime or ceftazidime 2gm IV q8h

Ventriculitis/meningitis due to infected V-P shunt
Likely etiology: S. epidermidis, S. aureus, coliforms, diphtheroids, P. acnes
Treatment: vancomycin 500-750gm IV q6 + cefepime or ceftazidime 2gm IV q8h
Chronic Meningitis (symptoms and CSF pleocytosis>4wks)
Likely etiology: M. tuberculosis, cryptococci, neoplastic, unknown
Treatment: depends on etiology; usually no need for urgent treatment
Bacterial meningitis in HIV+ patient
Likely etiology: same as adults>50yr, also cryptococci, M. tuberculosis, syphilis, HIV aseptic meningitis, Listeria monocytogenes
Treatment: as for adult>50yr
Viral Meningitis/Encephalitis
Likely etiologies: HSV, VZV, enterovirus
Treatment: acyclovir 10mg/kg IV q8h x 14-21d (pending viral PCR's and cultures)

Bacterial Endocarditis
Clinical Manifestations
Signs/Symptoms: fever, chills, sweats, anorexia, weight loss, malaise, myalgias, arthralgias, heart murmur, arterial emboli, splenomegaly, petechiae, peripheral manifestations (Osler's nodes, subungual hemorrhages, Janeway lesions, Roth's spots) and signs of CHF.
Laboratory manifestations: anemia, leukocytosis, microscopic hematuria, elevated ESR, CRP, RF, circulating immune complexes, decreased serum complement
Microbiology
S. aureus (30-40%), viridans group strep, enterococci (1%), coagulase-staph, culture negative (2-20%)
Risk Factors
Structural heart disease, IVDU, indwelling vasc devices, bacteremia with other infection, prior history of infective endocarditis
Work-Up
Blood Cultures:
If not critically ill: 3 blood cultures over 12-24 hours (can delay treatment)
If critically ill: 3 blood cultures over 1 hour (treat)
Echo (TTE or TEE)
EKG: evaluate for conduction abnormalities, ischemia, infarction
CXR: evaluate for septic emboli, valvular calcification, CHF
Diagnosis
Modified Duke Criteria (2 major OR 1 major and 3 minor OR 5 minor criteria)

Major Criteria
Positive blood cultures
Typical microorganisms from two separate blood cultures: viridans strep, Strep bovis, HACEK, or community acquired Staph aureus or enterococci in absence of primary focus
Persistently positive blood culture: recovery of organism from blood cultures drawn > 12hrs apart OR all of 3 or majority of 4 or more separate blood cultures with first and last > 1hr apart
Evidence of endocardial involvement
Positive echo: oscillating intracardiac mass or abscess or new partial dehiscence of prosthetic valve
New valvular regurgitation

Minor Criteria
Predisposing heart condition or injection drug use
Fever >= 38.0°C
Vascular phenomena: major arterial emboli, septic pulmonary infarcts, mycotic aneurysm, intracranial hemorrhage, conjunctival hemorrhages, Janeway lesions
Immunologic phenomena: glomerulonephritis, Osler's nodes, Roth's spots, RF
Microbiologic evidence: positive blood culture but not meeting above major criteria or serologic evidence of active infection with organism consistent with infective endocarditis
Empiric Treatment (for culture-positive endocarditis, use Sanford Guide to determine regimen)
Unless the pt has a toxic appearance or clinical or echo evidence of progressive valvular regurgitation or CHF, empiric antibiotics should be delayed until blood cultures are drawn. Administration of antibiotics before blood cultures are obtained reduces recovery rate of bacteria by 30-45%.

Native valve without IVDU:
[Penicillin G 20 million units q24h continuous or divided q4h OR ampicillin 12gm IV q24h continuous or divided q4h] AND oxacillin 2 gm IV q4h AND gentamicin 1mg/kg IV q8h
Alternative regimen is vancomycin + gentamicin

Native valve with IVDU (S. aureus)
Vancomycin 1gm IV q12h OR daptomycin 6mg/kg q24h

Prosthetic valve
Vancomycin 15mg/kg IV q12h + rifampin 600mg PO q24h + gentamicin 1mg/kg IV q8h
Indications for use of aminoglycosides for synergy
Shorter course regimen in right-sided endocarditis
Enterococcal endocarditis
Prosthetic valve
Prophylaxis (indirect evidence, no randomized trials)

Cardiac lesions for which endocarditis prophylaxis is advised:
High risk: prosthetic valves, prior bacterial endocarditis, complex cyanotic heart disease (except isolated secundum ASD and completely corrected PDA, VSD or pulmonary stenosis), PDA, coarctation of the aorta, surgically constructed systemic-pulmonary shunts
Moderate risk: congenital cardiac malformations, VSD, bicuspid AV, acquired AV and MV, hypertrophic CMY, MVP with valvular regurgitation and/or thickened leaflets

Procedures for which endocarditis prophylaxis is advised (moderate and high risk patients):
Dental procedures: extractions, periodontal procedures, implant placement, root canal, surgery beyond apex, subgingival placement of antibiotic fibers/strips, placement of orthodontic bands but not brackets, intraligamentary injections
Respiratory procedures: operations involving mucosa, rigid bronchoscopy
GI procedures: Esophageal variceal sclerotherapy, stricture dilatation, ERCP, biliary tract surgery, bowel surgery involving the mucosa
GU procedures: urethral dilation, prostate or urethral surgery, cystoscopy

Antibiotic regimens for prophylaxis of endocarditis in adults at moderate or high risk:
Oral cavity, respiratory tract, or esophageal procedures
Amoxicillin 2gm orally 1 hour before procedure
Unable to take oral medications: ampicillin 2gm IV or IM within 30mins of procedures
PCN allergy options:
Clarithromycin 500mg PO 1h before procedure
Cephalexin 2gm PO 1h before procedure
Clindamycin 600mg PO 1h before procedure or IV 30mins before procedure
Cefazolin 1gm IV/IM 30mins before procedure
GU/GI procedures
High risk: ampicillin 2gm IM/IV and (gentamicin 1.5mg/kg within 30min of procedure); repeat ampicillin 1gm IM/IV or amoxicillin 1g PO 6h later
High risk with PCN allergy: vancomycin 1gm IV over 1-2h AND gentamicin 1.5mg/kg IV/IM completed within 30 minutes of procedure
Moderate risk: amoxicillin 2g PO 1h before procedure or ampicillin 2g IV/IM within 30min before procedure
Moderate risk with PCN allergy: vancomycin 1g IV over 1-2h completed within 30 min of procedure
References
Matthew Leibowitz Noon conference lecture "Infective Endocarditis"
Baddour LM, Wilson WR, et. al. "Infective endocarditis: diagnosis, antimicrobial therapy, and management of complications: a statement for healthcare professionals from the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease in the Young, and the Councils on Clinical Cardiology, Stroke, and Cardiovascular Surgery and Anesthesia, American Heart Association: endorsed by the Infectious Diseases Society of America." Circulation. 2005;111:e394.
The Sanford Guide to Antimicrobial Therapy, 2006.

Clostridium Difficile
History
Recent exposure to antibiotics. Any antibiotic, but newer data show that fluoroquinolones and 3^rd generation cephalosporins (not clindamycin) seem to be most highly associated with this complication. However, exposure to other patients with C. difficile colitis in a hospital or other group facility can result in infection.
Signs/Symptoms:
Diarrhea, abdominal pain, fever, leukocytosis (can cause leukemoid reaction with WBC >30,000)
Diagnosis
Send 2 stool samples for C. difficile toxin (do not order C. difficile toxin x3!)
Sensitivity of one C. difficile toxin assay (our lab runs BOTH A and B, even though sometimes the computer reports toxin A) is about 80%, sensitivity of 2 is over 90%. Therefore, the lab will only run 2 samples in a 7 day period.
Management
Discontinue broad-spectrum antibiotic agent or change to another agent with a more narrow spectrum specifically targeting known or suspected etiology
Supportive measures: correct fluid losses and electrolyte imbalance
Avoid antiperistaltic agents
Contact isolation precautions for hospitalized patients
Avoid using vancomycin for treatment while patient is hospitalized to avoid selecting for VRE
Specific Treatment
Antimicrobial Agents

Metronidazole: 500 mg PO TID x 10 days: always the first drug of choice. PO is preferred to IV, but both work fairly equally. It may take several days for signs and symptoms to improve, rare Flagyl failure. Do not panic and add PO vancomycin (very expensive!) if pt. not better in 2 days. Treat for total 10 days. No need to repeat C. difficile toxin at end of Rx as test of cure, may still be positive.

Vancomycin: 125 mg PO QID x 7-14 days
Parenteral agent (to be used only until oral agents are tolerated): metronidazole 500 mg IV q6hrs
Older agents that may be added in severe disease- Rifampin or Bacitracin: 25,000 U PO QID x 7-14 days (see below)
Newer agents that may be effective: Rifaximin and nitazoxanide.
Recurrences and Relapses
Flagyl is still first drug of choice for repeat/recurrent C. difficile. Flagyl-resistant C. difficile rare, even after recent Rx with Flagyl, so choose Flagyl again
Vancomycin or Metronidazole PO x 10-14 days.
Vancomycin + rifampin (600 mg PO BID) x 7-14 days
Many protocols for long-term Rx for patients with several recurrences, lactobacillus unlikely to be helpful while pt. is still on antibiotics, and cholestyramine is of questionable efficacy, consult ID if assistance is required.
Emerging pathogen: more virulent epidemic C. difficile. Seen even in outpatients with no predisposing risk factors (N Engl J Med. 2005;353:2442).

Line Infections
Infected IV catheters are usually due to gram positive cocci, most often coagulase-negative staphylococcus or S. aureus
Empirically treat with vancomycin
If severe sepsis without other obvious source, remove CVC
Remove CVC if any evidence of infection at catheter site
References
Infectious Diseases Society of America, Society of Critical Care Medicine, Society for Healthcare Epidemiology of America. Guidelines for the Management of Intravascular Catheter-Related Infections. Clinical Infectious Diseases. 2001;32:1249.

Urinary Tract Infections
General Considerations
Although a urine Gram stain may be useful in guiding therapy, all antibiotics recommended as empiric therapy are effective against Gram-negative bacilli (pyelonephritis is not treated empirically with ampicillin or sulfonamides alone due to E. coli resistance to these antibiotics).
In patients with nosocomial pyelonephritis, a history of recurrent UTI, or prior infection with a resistant organism, initial antimicrobial therapy should cover Pseudomonas aeruginosa (I.e. cefepime, tobramycin, imipenem, ciprofloxacin, or piperacillin/tazobactam).
In all cases, antibiotic therapy should be revised once susceptibility data are available.
If bacteriuria persists > 24-48 hours, switch the antibiotic based on susceptibility data.
If fever or toxicity persists despite adequate antibiotics, consider perinephric or renal cortical abscess and evaluate with imaging of kidneys.
Signs of pyelonephritis (i.e. fever, leukocytosis) may not be present in the elderly.
Categories and Empiric Treatment

Acute, uncomplicated cystitis in women
Dysuria, urgency, frequency, suprapubic pain
No prior urinary symptoms in last 4 weeks
No fever or flank pain
Treatment:
3 days of oral TMP/SMX (DS) OR FQ
DM, >7 days of symptoms, recent UTI, age > 65, or diaphragm use: treat for 7 days with above
Pregnant: 7 days of oral amoxicillin, nitrofurantoin, cefpodoxime, OR TMP/SMX (do not use near term)

Acute, uncomplicated pyelonephritis in women
Fever, chills, dysuria, urgency, frequency, suprapubic pain, CVA tenderness and/or flank pain
No history of urologic abnormalities
Treatment:
Mild/moderate symptoms without nausea/vomiting: oral FQ x7 days OR amoxicillin/clavulanate or cephalexin or TMP/SMX (DS) x14 days
Severe/urosepsis requiring hospitalization: IV FQ OR (ampicillin + gentamicin) OR 3^rd generation cephalosporin OR piperacillin/tazobactam until afebrile then oral TMP/SMX (DS) or FQ x14 days
Pregnancy: IV ceftizoxime OR gentamicin +/- ampicillin OR aztreonam OR TMP/SMX until afebrile then oral amoxicillin OR cephalosporin OR TMP/SMX (DS) x14 days

Complicated UTI
Any combination of findings in above categories
Men or patients with post-void residual > 100 mL, outlet obstruction, calculus, urinary catheter, vesicoureteral reflux, prior renal disease with azotemia
Treatment:
Mild/moderate symptoms without nausea/vomiting: oral FQ x10-14 days
Severe/urosepsis requiring hospitalization: IV ciprofloxacin OR (ampicillin + gentamicin) OR ceftizoxime OR aztreonam OR piperacillin/tazobactam OR imipenem until afebrile then oral TMP/SMX (DS) or FQ x14-21 days

Asymptomatic
Treat only those who are pregnant, diabetic, and/or immuno-compromised.
Asymptomatic Bacteriuria

Definition: >10⁵ bacteria/mL of urine obtained by sterile technique on consecutive samples.
If symptomatic, treat the patient.
If asymptomatic, treat only those patients who are pregnant, have obstructive uropathy, or prior to genitourinary instrumentation.
Prevalence is increased in elderly or patients with a condom catheter or indwelling Foley catheter. Women with diabetes have 3-fold higher rates of asymptomatic bacteriuria and may benefit from an initial attempt at eradication with a 2-week course of antibiotics.
Often, bacteriuria is difficult to eradicate and routine antimicrobial therapy is not recommended.
Pyuria

Diagnosis: leukocyte esterase positive on dipstick (50% PPV; 92% NPV).

Definition: more than 10 WBCs per mm³ of urine
Most symptomatic women with pyuria but without bacteriuria do have UTIs, either with bacteria at levels less than 10⁵/mL or with Chlamydia trachomatis.
Patients with catheter-associated bacteriuria and pyuria are more likely to have true infection.
Differential diagnosis of "sterile" pyuria includes: perinephric and renal cortical abscesses, urethral syndrome, chronic prostatitis, renal tuberculosis or fungal infection, renal papillary necrosis (esp. diabetes, sickle cell disease, chronic alcoholism), genital herpes, chlamydia, uric acid and hypercalcemic nephropathy, lithium and heavy metal toxicity, GU malignancy, sarcoidosis, transplant rejection, interstitial cystitis, polycystic kidney disease, and s/p TURP (several months).
Candiduria

Diagnosis:
Species include: C. albicans, C. tropicalis, C. parapsilosis, and C. glabrata.
May represent contamination, colonization, cystitis, pyelonephritis, or disseminated infection. Candida may contaminate urine cultures as a result of coincident perineal colonization, vulvovaginitis or balanitis (esp. diabetes). If candiduria is noted, first confirm with clean-cath specimen.
In the absence of an indwelling bladder catheter, a colony count > 10,000/mL typically indicates infection.
Risk factors favoring colonization of the bladder: diabetes, indwelling catheter, broad-spectrum antibiotics, immunosuppressive therapy, and pregnancy.
In elderly and diabetic patients, this diagnosis may be elusive and is suggested by vague constitutional symptoms, a decline in renal function, and persistence of candiduria despite topical antifungal therapy, e.g., amphotericin bladder irrigation.
Disseminated candidiasis is suspected in patients with risk factors for blood-borne disease: malignancy (esp. leukemia/lymphoma), postoperative status, intravascular catheters, immunosuppression, broad-spectrum antimicrobial therapy, and malnutrition.
Check RUA for pyuria®funguria without pyuria is unlikely an infection.

Treatment:
Asymptomatic candiduria is treated by eliminating the predisposing factor.
Cystitis: as above and Fluconazole 200 mg p.o., then 100 mg p.o. qd x 4-7 days.
Pyelonephritis and disseminated disease: Fluconazole (800mg iv x 1 dose, then 400 mg IV qd x 7d, then 400 mg p.o. qd x 14d) or Amphotericin B (0.5 mg/kg IV qd to a total cumulative dose of 5-7 mg/kg).
For non-candida fungal UTI (e.g. C. glabrata):
First try hi dose (2x normal dose) fluconazole
Then try low dose IV Amphotericin B
Then consider Amphotericin B bladder irrigation but use with caution in Renal transplant or pt. with abnormal GU anatomy. IV Caspofungin has virtually no penetration into urine/bladder and has little role in Rx of candiduria.

Lactose Fermenting Status of Gram Negative Organisms
Lactose Positive (CEEK)	Lactose Negative (SPAM)
Citrobacter freundii Escherichia Coli Enterobacter Klebsiella pneumoniae, oxytoca	Serratia Salmonella Shigella Stenotrophomonas maltophilia Proteus Providencia Pseudomonas Plesiomonas Acinetobacter Aeromonas Morganella

Quick Guide to empiric antibiotic management
Adapted from Martha Lewis Noon conference lecture "Guide to Empiric Antibiotic Management"
General Considerations: What are you treating and how?

Site of Infection: drug penetration, common organism

Host: immune status, past pathogens, drug-drug interactions, allergies

Susceptibility data

Infection	Bugs	Drugs
Meningitis*	S. pneumoniae N. Meningitidis, H. influenzae Listeria	Ceftriaxone + vancomycin +/- ampicillin
If post-op	Staphylococcus sp. Gram negative rods (GNR)	Ceftazidime + vancomycin
Ventriculitis due to an infected VP shunt	S. epidermidis S. aureus Coliforms$ Diphtheroids P. acnes	Vancomycin + rifampin
Encephalitis (viral)	Herpes simplex virus Varicella zoster virus West Nile virus	Acyclovir
Sinusitis	S. pneumoniae	Amoxicillin or Augmentin (if prior antibiotic exposure)
Mastoiditis	M. catarrhalis Staphylococcus sp.	Ceftriaxone +/- vancomycin
Pharyngitis	Group A, C, G streptococcus	Penicillin
	N. gonorrhoea	Ceftriaxone (IM) + treat for Chlamydia with azithromycin OR doxycycline
Retropharyngeal/neck abscess	Streptococcus sp. Oral anaerobes	Clindamycin
Pneumonia
Community-acquired	S. pneumoniae H. influenzae Chlamydia Mycoplasma Legionella	Levaquin OR Ceftriaxone + azithromycin
Hospital-acquired (48 hours)	S. pneumoniae S. aureus Enteric GNR (i.e. klebsiella)	Levaquin + Zosyn OR Ceftriaxone/ceftazidime + vancomycin +/- gentamicin
Ventilator-associated (48-72 hours)	P. aeruginosa MRSA Acinetobacter Multidrug resistant GNR Stenotrophomonas	Imipenem + levofloxacin +/- (vancomycin OR linezolid if suspect MRSA)
Pneumonitis	PCP Cytomegalovirus	High-dose Bactrim OR High-dose Ganciclovir
Endocarditis	S. aureus (MRSA) Viridans streptococcus Enterococcus Coagulase-negative staph Enteric GNR	Blood cultures first! Vancomycin + gentamicin + rifampin (if valve)
	Candida	Caspofungin
Line Infections	Coagulase-negative staph S. aureus	Vancomycin
Neutropenic Fever	Enteric GNR P. aeruginosa Staphylococcus sp. Viridans streptococcus	(Ceftazidime +/- gentamicin) OR Imipenem/Zosyn/Cefepime +/- vancomycin (if possible line infection)
Sepsis	Enteric GNR P. aeruginosa Staphylococcus sp. Viridans streptococcus	Ceftriaxone + gentamicin + metronidazole
Diarrhea	Campylobacter E. coli Salmonella Shigella Giardia C. difficile	Mild to moderate diarrhea®no antibiotics! Severe diarrhea use ciprofloxacin and/or metronidazole (if C. difficile suspected)
Diverticulitis	Enteric GNR Anaerobes Enterococcus sp.	Ciprofloxacin + metronidazole (outpatient) Zosyn OR imipenem (inpatient)
Biliary Sepsis	Enteric GNR Anaerobes Enterococcus sp.	(Ceftriaxone + metronidazole) OR Zosyn
Spontaneous Bacterial Peritonitis (SBP)	Enteric GNR Streptococcus sp. Enterococcus sp.	Ceftriaxone (Prevention of SBP with Bactrim 5 days per week or weekly ciprofloxacin)
Cystitis	Enteric GNR Enterococcus sp. S. saprophyticus	Ciprofloxacin Cephalexin Cefpodoxime
Pyelonephritis	Enteric GNR Enterococcus sp. S. saprophyticus	(Ceftriaxone + gentamicin) OR (ampicillin + gentamicin)
STD	N. gonorrhoea C. trachomatis	Ceftriaxone (IM) Azithromycin OR doxycycline
Cellulitis	S. aureus Streptococcus sp.	Cefazolin (IV), cephalexin (PO)
Boils, Furuncles, Spider bites	MRSA	Vancomycin Bactrim Doxycycline Rifampin Linezolid
Diabetic Foot	Mixed flora: MSSA/MRSA Enteric GNR Anaerobes	Augmentin Ceftriaxone + metronidazole +/- vancomycin
Necrotizing Fasciitis	Streptococcus sp. S. aureus Clostridium Anaerobes	Imipenem OR Penicillin + clindamycin + (fluoroquinolone OR 3rd generation cephalosporin OR aminoglycoside) Consider IVIG & Xigris
Osteomyelitis	MSSA/MRSA	Oxacillin OR vancomycin
with diabetic foot	Enteric GNR Anaerobes P. aeruginosa	(Oxacillin OR vancomycin) + metronidazole and ceftriaxone
with hardware	Enteric GNR Anaerobes P. aeruginosa Coagulase-negative staph	Vancomycin + cefotaxime
*Dexamethasone (N Engl J Med 2002;347:1549) $Coliforms include Escherichia, Enterobacter, Klebsiella, Citrobacter

Antibiotic Dosing In Renal Replacement Therapy
Trotman RL et al. "Antibiotic Dosing in Critically Ill Adult Patients Receiving Continuous Renal Replacement Therapy." Clinical Infectious Disease 2005: 41: 1159-66.