Lanny Hsieh, M.D. Infectious Diseases Hospitalist Program

Definition of Fever

Arbitrary 38.0-38.4 (low grade – may be

significant in immunocompromised patients)

> 38.5 (nurse will call you)

Be aware of signs of infection without fever Patient types:

Immunocompromised Elderly Large burns or wounds On anti-inflammatory, immunosuppression, steroids.

Signs: Hypothermia, rigors. Tachycardia Hypotension Tachypnea Confusion Oliguria Labs: lactic acidosis, leukopenia, leukocytosis,

bandemia.

Blood cultures

Sensitivity determined by many factors: Degree of bacteremia Antibiotics before culture Volume of blood drawn.

Pediatric collection tubes should not be used for adults due to poor yield.

Consider fungal blood culture if: Immunocompromised Prolonged hospitalization Indwelling lines Prolonged antibiotics.

If no lines, draw 2 sets of peripheral cultures. If indwelling lines, draw one set from line, one set

periphery. If in ICU w multiple lines, send one set from each line

and label source. No indication for TB or viral (CMV) blood cultures

in routine fever workup.

Lines and Fever

Intravascular Devices and Fever Relative risk of line infections by catheter:

Quintons, CVL, art lines, PICC: 2-5 /1000 cath-days Implanted ports: 0.2-1 per /1000 cath-days Peripheral IVs: <0.1 per 1000 catheter days

Suspicion for line infection Abrupt onset of sepsis without obvious source. Difficulty drawing or infusing through a catheter. Exudate and/or erythema at exit site.

Catheter tips should only be cultured if there is clinical suspicion for line infection.

Empiric removal of lines is only indicated in septic, unstable patients.

IDSA Guidelines for Intravascular Catheter-Related Infection • CID 2009:49 (1 July)

Definitions of catheter-related infections

Infection Definition

Catheter colonization: Significant growth of an organism. Phlebitis: Induration, erythema, and tenderness along vein. Exit-site infection: Exudate, redness, induration at the

catheter exit site. Tunnel infection: Tenderness, erythema, induration along

subcutaneous tract of a tunneled catheter. Pocket infection: Infection in the subcutaneous pocket of a

implanted intravascular device Bloodstream infection

Phlebitis

Tunnel Infection

Pocket Infection

Diagnosis of Catheter-related Bacteremia

Patient has an intravascular device. At least one positive peripheral blood culture. Clinical manifestations of infection (fever, chills, and/or

hypotension). No apparent source for bacteremia other than the

catheter. One of the following:

Catheter tip (if removed) grew same organism as blood.

OR Differential time to positivity

IDSA Guidelines for Intravascular Catheter-Related Infection • CID 2009:49 (1 July)

Most common pathogens isolated from bloodstream infections.

Pathogen 1986–1989, % 1992–1999, % Coag neg staphylococci 27 37 Staphylococcus aureus 16 13 Enterococcus 8 13 Gram-negative rods 19 14 E. coli 6 2 Enterobacter 5 5 P. aeruginosa 4 4 K. pneumoniae 4 3 Candida spp. 8 8

Prevention Guidelines for Catheter-Related Infections • CID 2002:35 (1 December)

Short term catheter infection

80. Duration of abx can be shorter (min 14d) if no DM, not immunosuppressed, catheter is removed, no intravascular device, no endocarditis on TEE, no thrombophlebitis on U/S, fever and bacteremia resolve in 72 hrs w abx, no evidence of metastatic infection.

Complicated = Remove

Health Care Associated Pneumonia

Cough, O2 sats, increased secretions. Immunocompromised patients may not have fever, cough,

sputum, or leukocytosis. Physical exam, Chest Xray, sputum culture. Negative chest xray does NOT rule out pneumonia,

especially in immunocompromised patients. Consider chest CT in certain patients.

Positive sputum culture does NOT mean pneumonia. Most organisms can be colonizers as well as

pathogens. Pleural effusions: only sample in certain patients. Not

part of routine fever workup.

Empiric Antibiotics for Hospital acquired pneumonia?

Presence of a new or progressive radiographic infiltrate plus at least 2 of: Fever greater than 38C leukocytosis or leukopenia Purulent secretions

represent the most accurate clinical criteria for starting empiric antibiotic therapy.

Am J Respir Crit Care Med Vol 171. pp 388–416, 2005 (ATS Guidelines)

Am J Respir Crit Care Med Vol 171. pp 388–416, 2005

RISK FACTORS FOR MULTIDRUG-RESISTANT PATHOGENS CAUSING HAP, HCAP, AND VAP.

Virtually all of our patients fit in this category!

Antimicrobial therapy within 3 months. Current hospitalization >5 days. High frequency of antibiotic resistance in the hospital. Hospitalization for >2 days in last 3 months. Nursing home resident. Home infusion therapy (including antibiotics). Dialysis within 30 days. Home wound care. Family member with MDR pathogen. Immunosuppressive disease and/or therapy.

INITIAL EMPIRIC THERAPY FOR HAP, VAP, HCAP IN PATIENTS WITH RISK FACTORS MDR PATHOGENS

Potential Pathogens Streptococcus pneumoniae Haemophilus influenzae MSSA Enteric gram-negative bacilli

MDR pathogens Pseudomonas aeruginosa MRSA ESBL Klebsiella pneumoniae and E. coli Acinetobacter species

Am J Respir Crit Care Med Vol 171. pp 388–416, 2005

INITIAL EMPIRIC THERAPY FOR HAP, VAP, HCAP IN PATIENTS WITH LATE-ONSET DISEASE OR RISK FACTORS FOR MDR PATHOGENS.

Antipseudomonal cephalosporin (cefepime, ceftazidime) or

Antipseudomonal carbepenem (imipenem, meropenem) or

B-Lactam/lactamase inhibitor (piperacillin–tazobactam) plus

Antipseudomonal fluoroquinolone (ciprofloxacin, levofloxacin) or

Aminoglycoside (amikacin, gentamicin, tobramycin) plus

Linezolid or vancomycin

Am J Respir Crit Care Med Vol 171. pp 388–416, 2005

Is there advantage to empiric antibiotics?

What if we waited for cultures?

Starting the right antibiotics in a timely manner

ICU setting, teaching hospital, St. Louis. 107 consecutive pts w VAP. All 107 pts eventually appropriate antibiotics. 33 (31%) received abx that was delayed for >24 hr.

25 (76%) delay in writing abx orders. 6 received antibiotics not active against the resistant

organism. 2 abx not given after order written.

Mortality attributed to VAP: 13 (39%) in delay group compared to 8 (11%) in non-delay group. (P .001)

Hospital mortality: 23 (70%) in delay group compared to 21 (28%) in non-delay group. (P<0.01)

Chest. 2002 Jul;122(1):262-8.

Urinary Tract Infections Catheter associated bacteriuria or candiduria:

Usually colonization. Rarely symptomatic. Rarely a cause of fever or secondary sepsis unless: ○ Urinary obstruction ○ Recent urologic manipulation ○ Neutropenic patient ○ Kidney transplant patient

Pyuria and bacteriuria count not reliable for infection. If patient is awake and alert, true infection should be

symptomatic. When diagnosis is questionable, consider changing foley

and recheck urine. If all parameters (pyuria, bacteruria, etc.) are better, then unlikely true infection.

Prevalence of asymptomatic bacteriuria in selected populations. Population Prevalence, %

Healthy, premenopausal women 1.0–5.0

Pregnant women 1.9–9.5

Postmenopausal women aged 50–70 years 2.8–8.6

Diabetic patients

Women 9.0–27

Men 0.7–11

Elderly persons in the community (age 70 yrs)

Women 10.8–16

Men 3.6–19

Elderly persons in a long-term care facility

Women 25–50

Men 15–40

Patients with indwelling catheter use

Short-term 9–23

Long-term 100

IDSA Guidelines for Asymptomatic Bacteriuria • CID 2005:40 (1 March)

Clostridium difficile colitis

C. diff accounts for 20%–30% of abx-associated diarrhea

and most common cause of infectious diarrhea in healthcare settings.

Risk factors: age, length of hospitalization, antibiotics

(duration and many abx), chemo, PPI (controversial). Manifestations: from asymptomatic to mild/moderate

diarrhea, to fulminant pseudomembranous colitis.

Bartlett JG. N Engl J Med 2002;346:334–349.

Fever, cramping, abdominal discomfort, and leukocytosis are common but found in fewer than half of patients.

Suspected in pts w fever or leukocytosis and diarrhea

who received antibiotics or chemo within last 60 days. Some patients may not have diarrhea: ileus or toxic

megacolon. May occur w any antiobiotic, most common are clinda,

FQ, and cephalosporins.

Testing for C. difficile or its toxins should be performed only on diarrheal (unformed) stool.

EIA testing for toxin A and B is rapid but not sensitive. PCR testing appears to be rapid, but may be overly

sensitive. May be picking up colonizers. 2-step method that uses antigen detection of glutamate

dehydrogenase (GDH) and toxin as initial screening and then uses the cell cytotoxicity assay or toxigenic culture is preferred.

Once confirmed, no utility in followup stool assays, follow clinically.

C. difficile Diagnosis

C. difficile Treatment

Discontinue inciting antibiotics if possible. Severity criteria: age, WBC>15, creatinine 1.5x baseline Complications: hypotension, shock, ileus, megacolon. Metronidazole for the initial episode of mild-to-moderate

CDI. Vancomycin for an initial episode of severe CDI. Dosage is

125 mg orally 4 times per day for 10–14 days. Vancomycin orally with IV metronidazole for the treatment

of severe, complicated CDI. Consider vancomycin enemas.

Infection control and hospital epidemiology may 2010, vol. 31, no. 5

C. difficile Recurrence: ~25%

Treatment of the first recurrence is with the same regimen as the initial episode but based on disease severity.

Treatment of the second or later recurrence of CDI with po vancomycin therapy using a tapered and/or pulse regimen is the preferred next strategy.

No recommendations regarding prevention of recurrent CDI in patients who require continued antibiotics for underlying infection.

Fidaxomicin: cure rates similar to oral vanco. May be better at decreasing rate of recurrence. Better for bowel flora.

C. difficile: controversial strategies

Probiotics: limited data to support, risk of bacteremia in immunosuppressed pts.

Rifaximin chaser following oral vanco: caution, data

shows increased MIC. Fecal transplants: success in case series. UCI GI

division has research protocol in place. IVIG: no clear data to support.

Other causes of diarrhea and fever?

Lots of bacteria, viruses, parasites can cause diarrhea and fever, but these are community acquired.

In immunocomprised patients (ie AIDS), can send stool

studies for “immunocompromised panel” and ovum and parasite. These can reactivate due to acute illness.

Sinusitis Prevalence is low in comparison w other nosocomial

infections. Risk factors:

Most common: anatomic obstruction by nasal tubes. Maxillofacial trauma and retained blood clots.

Etiological agents: Organisms that colonize the nasopharynx -- often polymicrobial. GNRs, including Pseudomonas aeruginosa (60%) S. aureus and coag negative staph (30%) Fungi (5-10%)

Preferred diagnosis by CT scan of sinuses. If does not respond to empiric treatment, may need

aspiration.

CNS infection and fever

Nosocomial meningitis is rare in patients without immune compromise or CNS instrumentation.

For patients with intracranial devices, need CSF

sample: Ventriculostomy tubes Ommaya reservoirs May also need LP if suspect obstruction of CSF flow

Occult Sources of Infection

Otitis media Decubitus ulcers Perineal or perianal abscesses Retained foreign bodies (tampons, contact lens) Intra-abdominal or pelvic abscesses. Septic thrombophlebitis Etc.

Drug Fever Any drug can cause fever. Most often attributed to:

Antibiotics (beta-lactams) Anti-epileptic (phenytoin) Anti-arrhythmics (procanamide) Anti-hypertensives (methyldopa)

Fevers may not occur immediately. One series, lag time between fever and drug

administration was mean 21 days (median, 8) Fever often takes 1-3 days to resolve, but can take

>7days after removing the offending agent. Rash occurs in small fraction of cases. Eosinophilia is uncommon.

Drug-related Fevers…

Neuroleptic malignant syndrome Malignant hyperthermia Serotonin syndrome Drug withdrawl syndromes (alcohol, opiates,

benzodiazepines)

Fevers not due to infection… Acalculous cholecystitis Myocardial infarction Pulmonary emboli Stroke, especially intracranial bleed Pancreatitis Thyroid or adrenal disease Transplant rejection Tumor lysis syndrome Venous thrombosis Blood product transfusion Immune reconstitution inflammatory syndrome Etc…

Nurse tells me my patient is febrile, what should I do?

Check the other vital signs: low BP? Tachy? Tachypneic? O2 sats changed? Drop in urine output?

Talk to the patient: any localizing symptoms? (cough, SOB, CP, diarrhea, headache, etc.)

Physical exam: tender belly? Rhonchi? New murmur? Leg edema? Rash? Wounds?

Diagnostics: blood cultures, lactate, UA and culture, CXR, EKG (if indicated), etc.

Therapeutics: antibiotics, fluid resuscitation, etc.

Approach to New Fever…

Before starting empiric antibiotics…

What am I treating? How sick is patient? Immune status Resistance pattern

community vs nosocomial Previous antibiotic exposure

Antibiotic choice (last)

Some Common Scenarios…

Fever 80 yo WM admitted from nursing home with

altered mental status. Pt is somnolent, not much history could be obtained from patient or family. Nursing home staff reports possible aspiration event. PMH: HTN, DM, CAD.

On exam T 39F, BP 90/60, P 120. Negative exam except for obtundation, bibasilar crackles, and chronic indwelling foley.

CXR shows pulmonary edema. Labs: WBC 15. All other labs and cultures

pending. Do you start antibiotics? If so, what?

What am I treating? Aspiration pneumonia, UTI. MRSA, pseudomonas, anaerobes, gram negatives.

How sick is patient? Low BP, tachycardia, AMS severe sepsis = sick.

Immune status Old, but otherwise not immunocompromised.

Resistance pattern community vs nosocomial Previous abx exposure ○ Nursing home = nosocomial, likely lots of abx

exposure. Antibiotic choice

Vancomycin + Meropenem (or equivalent)

Don’t forget Sepsis Resuscitation Bundle for this patient!!!

Fever

70 yo WF admitted 4 days ago for CHF exacerbation. Nurse calls you for fever to 39F.

You see the patient, who is comfortably sitting in bed. She denies HA, cough, SOB, CP, nausea, vomiting, diarrhea, dysuria. No central lines, no foley.

BP 130/70, P 80, O2 sat 97% on room air. Exam is normal except for bibasilar crackles.

Urine and blood are sent for culture. CXR is ordered.

Do you start antibiotics? If so, what?

What am I treating? No idea.

How sick is patient? Not sick.

Immune status Not immunocompromised.

Resistance pattern community vs nosocomial Previous abx exposure ○ Nosocomial.

Antibiotic choice Hold off. Await culture results.

The End