Temujin T. Chavez, M.D.

LCDR MC USN

Infectious Diseases Fellow

First 24 Hours HPI: Pt is a 48 yo female with reported anorexia nervosa who

presented to Dewitt c/o 1 wk nonprod cough, weakness and recent orthostasis. Int Med Clinic Dewitt eval s/f SaO2 84% RA to 87% 4 L NC. SBP 125 and Pulse 125

ROS: exposure to cousin with uri symptoms 10 days prior while traveling to Indiana. Denies hospitalized contacts or contacts evaluated in ED. (-) Influenzae vaccination

Dewitt ER: 7.39/43.8/49/26.4. Nasally intubated and transferred to WRAMC.

WRAMC: Piperacillin-Tazobactam 3.375 gm iv <4hrs, Vancomycin 1 gram <8hrs, Ceftriaxone 1 gram @ 9 hrs

First 24 Hours PMHx:

Anorexia Nervosa

Ovarian Ca s/p TAH

HTN

HLD

SurgHx: TAHBSO 1986

Breast Bx Feb 2008

SocHx: (-) Tobacco/etoh

FHx: Sister (+) breast ca

First 24 hours T=97.7, BP=81/52, P=111, I/O (3 hrs)

1224 LR/300 UO

SIMV PS. Rate 12. PS 10cmH20. PEEP 5cmH2o. FIO2 100%

Gen: sedated. GCS 10T(E3, M6,VT)

APACHE IV score=76

APS Score=71

ABG 7.332/35.7/92/18.9/97%

SvO2=48.9

WBC=1.9, HCT=31

Na=125, BUN=24, Cr=1.4, Glc=115

Alb=2.2, Bili 0.6

Blood culture 4 of 4 bottles Streptococcus

pneumoniae Penicillin (0.5mcg/ml), Vanc

(0.5mcg/ml), Ceftriaxone (0.016 mcg/ml), Levofloxacin (1.0 mcg/ml)

Resp culture 2+ PMN, 1+ EPI, Mixed flora

Streptococcus pneumoniae

First 24 Hours

Hospital Day 3 Consult Question

Optimal antibiotic therapy in pt with PCN sensitive bacteremic pneumococcal pneumonia on Piperacillin-Tazobactam/Ceftriaxone/Vancomycin?

CAPEmpiric Antibiotic Therapy

CID 2007;44:S27-72

Combination Antibiotic Therapy•Prospective observational study

•Dec 1998 – Dec 2000

•844 w/ bacteremia 2nd to Streptococcus pneumoniae

•Pts monitored for 14 days post bacteremia or longer if hospitalized

•Monotherapy

•Same single abx w/in 1st 2 days of + BCx

•Combination therapy

•Same 2 abx w/in 1st 2 days of +BCx

•Figure A

•Survival plot for pts not critically ill

•Figure B

•Survial plot for pts critically ill

AM J Resp Crit Care 2004;170:440-44

Combination Antibiotic Therapyin Critically Ill Monotherapy

B-lactam (43)

Azithromycin (2)

Ciprofloxacin (1)

Clindamycin (1)

Combination Therapy

B-lactam/macrolide (14)

B-lactam/Vancomycin (12)

B-lactam/ Aminoglycoside (7)

Vancomycin/other (4)

Vancomycin/fq (4)

Dbl B-lactam(2)

Combination Antibiotic Therapy

Am J Resp Crit Care 2004;170:440-44

Empiric TherapyChoosing The Right Combination•Retrospective observational study

•Jan 1999 – Dec 2002

•172 subjects having rad and ICD-9 diagnosis of CAP

•Abx administered 1st 48hrs of admission

•33% w/in 4 hrs of presentation

•Multivariate logistic regression model to assess 30 day mortality between B-lactam and FQ VS. other guideline therapy

•B-lactam + FQ (30%)

•B-lactam + Macrolide (17.2%)

•Other regimens (11.4%)

Crit Care 2006;10:1186-94

Empiric TherapyChoosing The Right Combination

Crit Care 2006;10:1186-94

Addition of macrolide to B-Lactam-Based Empiric Treatment•Retrospective observational study

•1991-2000

•409 pts w/ S. pneumoniae bacteremic pneumonia

•B-lactam +/- other antibiotic

•Pts observed from time of dx of bacteremia until death or d/c

•238 (58%) received B-lactam + macrolide

•171 (42%) received B-lactam +/-other abx

CID 2003;36:389-95

Addition of macrolide to B-Lactam-Based Empiric Treatment•Pts who did not receive a macrolide

•HIV

•Hematologic malignancies

•Neutropenia

•Nosocomial infection

•Pts who received a macrolide

•Shock at time of presentation

•Admitted to ICU

•Univariate analysis in hospital mortality

•Shock (p<.0001)

•Abx other than macrolide (p<.001)

•Infxns R to PCN&Erythro (p=.02)

•ICU admission (p<0.0001)

CID 2003;36:389-95

Addition of macrolide to B-Lactam-Based Empiric Treatment•Association btwn initial macrolide therapy and a lower in-hospital mortality rate remained sig after exclusion of pts who died </= 48 hrs p admission

•Macrolide and PCN resistance

•More virulent strains

•Resistance to macrolide negates the beneficial effect of macrolides

•Pts infected w/ resistant strains had a more serious disease

CID 2003;36:389-95

References Mandell LA, et al. Infectious Disease Society of America/American

Thoracic Society Consensus Guidelines on the Management of Community-Acquired Pneumonia in Adults. CID 2007;44:s27-72.

Mortensen EM, et al. The Impact of Empiric Antimicrobial Therapy With a B-Lactam and Fluoroquinolone on Mortality for Patients Hospitalized with Severe Pneumonia. Crit Care 2006;10:1186-94.

Martinez JA, et al. Addition of a Macrolide to a B-Lactam-Based Empirical Antibiotic Regimen Is Associated with Lower In-Hospital Mortality for Patients with Bacteremic Pneumococcal Pneumonia. CID 2003;36:389-395.

Baddour LM, et al. Combination Antibiotic Therapy Lowers Mortality among Severely Ill Patients with Pneumococcal Pneumonia. AM J Resp Crit Care Med 2004;170:440-44.