Transcript No Slide Title

Update on Antibiotic Treatment of
Emergency Department Infections
David A. Talan, MD, FACEP, FIDSA
Professor and Chair
UCLA School of Medicine
Olive View-UCLA Dept. of Emergency Medicine
and Division of Infectious Diseases
Time to Antibiotics for CAP:
Mortality and Length of Stay
Adjusted Mortality Odds Ratio
Initial abx < 8 hrs
(75.5%)
0.85
(0.75-0.96)
P
<0.001
Meehan TP. JAMA 1997;278:2080.
ED Abx (n=473)
LOS <9 days
71%
(ED 3.5 + 1.4 vs. after 9.5 + 3.0 hrs)
Battleman DS. Arch Intern Med 2002:162:682.
LOS >9 days
(n=136)
51%
(OR 0.31*)
What's New in 2003?

Emerging bacterial resistance

New antibiotics

Short-course regimens

Outpatient management

Practice guidelines

Restricting diagnoses/antibiotic use
Newer Antibiotics
Quinolones
with
enhanced
pneumococcal
activity

Levofloxacin (Levaquin)
Moxifloxacin (Avelox)

Gatifloxacin (Tequin)

Ertapenam (Invanz)

Augmentin XR (1000 mg amoxicillin,


Cipro
dose: 2 tabs Q 12 hours)
XR (500-1000 mg QD)
Once-Per-Day Antibiotics
Oral
Parenteral
Azithromycin (Zithromax)
Cefadroxil (Duricef)
Aminoglycosides
Cefixime (Suprax)
Ceftriaxone (Rocephin)
Ceftibuten (Cedax)
Ertapenam (Invanz)
Cefdinir (Omnicef)
Levofloxacin (Levaquin)
Moxifloxacin (Avelox)
Gatifloxacin (Tequin)
Clarithromycin ER (Biaxin XL)
Emerging Bacterial Resistance

DRSP (including QR-DRSP)

Macrolide-res. S. pneumoniae/pyogenes

TMP/SMX/FG ceph./Quinolone-res. E. coli

Quinolone-res. N. gonorrheae (QRNG)

Community-acquired (CA-MRSA)
Acute Otitis Media: New Concepts

Dx: inflamed and immobile TM

New higher dose, shorter duration

No treatment OK - 2 day follow-up
Wait and See Approach for
Acute Otitis Media in British Children
 Non-blind, randomized
 6 months to 10 years
 Pain & erythema,
bulging or perforation
Immediate Rx
(98% used, n=135)
Pick up Rx in 3 day
(24% used, n=150)
Days of earache
2.6
3.6
Nights disturbed
1.6
2.5
Days school missed
2.0
2.1
Diarrhea (%)
19
9
Very satisfied (%)
91
77
Would need MD in future (%)
83
63
Little P. BMJ 2001:322:336.
Acute Otitis Media: 1999 US
CDC Working Group

1st line - HD amoxicillin - 80-90 mg/kg/day (BID,
to 2 grams, up to 1 grams TID) A/C >AZ bac and clin. cure
Ped Infect Dis J 2000:19:95.


2nd line - HD amoxicillin/clavulanate, cefuroxime,
days > 1 day (DRSP)
IM ceftriaxone (50 mg/kg) Ped3Infect
Dis J 2000:19:1040.
Risk groups - day care, prior abx, < 2 years
Refractory cases - IM ceftriaxone QD X3,
clindamycin, tympanocentesis
Dowell SF. Pediatr Infect Dis J 1999;18:1.
Avoid: cefaclor, cefprozil,
cefixime, ceftibuten b/o DRSP activity
Community-Acquired Pneumonia
US Study to Predict Low-Risk
Pneumonia Patients


Less than 50 years of age
No history of cancer, CHF, cerebrovascular,
HIV, renal or liver disease

Normal mental status

P < 125, RR < 30, BP > 90, T 35-40oC
Fine MJ. NEJM 1997;336:243.
CAP Mortality Prediction Rule
Demographic:
Age (-10 women)
Nursing home
10
Co-morbidity:
Cancer
30
CHF
20
CVA, renal, liver 10
Fine MJ. NEJM 1997;336:243.
Exam:
MS, RR >30, BP< 90
20
HR >125
15
T < 35o or > 40oC
10
Lab:
pH < 7.35
30
BUN > 30, Na < 130
20
Glu>250, Hct <30,
10
pO2 <60, pleural effusion
CAP Risk Classes, Mortality, and
Management
Risk Class - score
I
II <70
III 71-90
IV 91-130
V >130
Fine MJ. NEJM 1997;336:243.
30 Day Mortality (%)
<0.5
0.5-1
1-4
4-10
>10
Rec. Care
Outpatient
Outpatient
Inpatient (brief)
Inpatient
Inpatient
Canadian CAP Clinical Pathway Trial
Marrie TJ. JAMA 2000;283:749.
ED Dx Pneumonia
22 hospitals, 1,743 patients
Pneumonia score (+Pox)
given to MD by nurse
<90 recommended d/c home
Standard care
Inpatient care - 31%
Inpatient care - 49%
2 &6 week QOL scores
37 & 43
2 &6 week QOL scores
38 & 41
US CAP Antimicrobial Strategies
Atypical Etiology
(Young age)
Pneumococcal Etiology
(Degree of Illness)
DRSP
(Prevalence, prior Abx/ hosp.)
Macrolide
Doxycycline
New fluoroquinolones
2nd-3rd GC/Macrolide
CAP: Outpatient Treatment in US
Oral regimens
10-14 days
treatment failures
high-risk
documented DRSP
Azithromycin 500/250 mg QD (5 d)
Clarithromycin 500 mg BID
Doxycycline 100 mg BID
-lactam (HD amox, amox/clav,
ceftriaxone -cefpodoxime
/cefuroxime) with above
Levofloxacin 500 mg QD
Moxifloxacin 400 mg QD
Gatifloxacin 400 mg QD
American Thoracic Society. Am J Respir Crit Care Med 2001;163:1730.
Bartlett JG. Clin Infect Dis 2000;31:347. CDC. Arch Intern Med 2000;160:1399.
Worldwide Outpatient
CAP Guidelines
Country/Org/Year
Recommendation
ACEP 2001
US IDSA 2000
Canadian ID/TS 2000
See US IDSA
Macrolide or doxycycline or FQ
Macrolide or doxycycline
mod. factor – FQ
“ or BLI+ macrolide
Amoxicillin
BLI + macrolide
Penicillin or erythromycin
Amoxicillin HD or macrolide
US ATS 2001
France 1991
Italy 1995
Spain 1992
UK BTS 2001
CAP: Inpatient Treatment in US
Floor

2nd/3rd gen. cephalosporin
plus azithro or doxy
Levofloxacin 500 mg Q24o

Gatifloxacin 400 mg Q24o

Moxifloxacin 400 mg Q24o

ICU
Ceftriaxone plus either
New Quinolone
or
Macrolide and aminoglycoside

ATS. Am J Respir Crit Care Med 2001;163:1730.
Bartlett JG. Clin Infect Dis 2000;31:347.
CDC. Arch Intern Med 2000;160:1399.
Finch R. Antimicrob Agents Chemother 2002;1746.
Consider vancomycin if
quinolone exposure
US Study of Relative 30-Day Mortality
by Initial Antibiotic Regimen for CAP
9,751 patients > 65 yrs, regimen
within 48 hrs of admission
Adjusted hazard ratio (95% CI)
3rd gen. ceph plus macrolide
0.66 (0.51-0.86)
Fluoroquinolone only
0.64 (0.36-1.14)
 -lactamase inh. plus macrolide
1.61 (1.08-2.39)
3rd gen. cephalosporin only
Gleason PP. Arch Intern Med 1999;159:2562.
reference
Cystitis Pathogen Antimicrobial
Resistance - Seattle 1992-6
40
AMP
30
CEPH
%
20
NITRO
10
T/S
CIPRO
92
93
Gupta K. JAMA 1999;281:736.
94
95
96
Shift to quinolones/nitrofurantoin/3rd gen. cephs.
Cystitis: Effect of T/S Resistance on Clinical
Success in T/S-Treated Patients In Israel
Raz R. Clin Infect Dis 2002;34:1165. (follow-up 4-6 weeks)
%
100
90
80
70
60
50
40
30
20
10
0
88%
(293/333)
Resistance matters
Low morbidity disease
54%
(81/151)
Susceptible
Resistant
Three-Day Cystitis Regimens
% Cure 2 weeks
TMP/SMX BS BID (n=39)
At least
7 days
82*
Nitrofurantoin 100 mg QID (n=36)
61
Cefadroxil 500 mg BID (n=32)
66
Amoxicillin 500 mg QID (n=42)
67
Hooton TM. JAMA 1995;273:41.
Therapy for Uncomplicated Cystitis
Routine culture not recommended
 3 days -more effective than 1 dose
less side effects than 7 days
TMP/SMX DS BID (if < 20% resistance)
Levofloxacin 250 mg QD
Ciprofloxacin XR 500 mg QD
Cost-effectiveness model
Ofloxacin 200 mg BID
supports at 22% T/S resistance rate
Clin Infect Dis 2002:33:615.
Gatifloxacin 400 mg QD
 7 days – Nitrofuratoin (low-cost/resistance)
Cephalexin (resistance), 3rd GC
 Culture if no symptom resolution in 2 days

Acute Uncomplicated Pyelonephritis in
US: Cipro 7 Days vs. TMP/SMX 14 Days
Talan DA. JAMA 2000;283:1583.
Bacteriologic cure
%
100
90
80
70
60
50
40
30
20
10
0
99%
(113)
p =.004
89%
(101)
85%
(111)
p =.08
74%
(108)
Clinical cure
96%
(113)
p =.002
83%
(111)
91%
(106)
p =.015
77%
(106)
PO +/- IV
Cipro
PO T/S +/IV Ceftriaxone
4-11 days
22-48 days
4-11 days
22-48 days
Effect of TMP/SMX Resistance in
TMP/SMX-Treated AUP Patients
p < 0.0001 (both)
Talan DA. JAMA 2000;283:1583.
%
100
90
80
70
60
50
40
30
20
10
0
96%
(73/76)
92%
(76/83)
Cost/patient
Resistance matters
High morbidity disease
Cipro $510 TMP/SMX $725
50%
(7/14)
Susceptible
35%
(6/17)
Resistant
Bacteriologic
cure
Clinical
cure
Outpatient ED Treatment of Acute
Uncomplicated Pyelonephritis
Initial PO/IV Dose
Oral regimens
(7days)
Ciprofloxacin 400 mg
Levofloxacin 250 mg
Gentamicin 5-7 mg/kg
Ceftriaxone 1 gram
Cipro XR 1000 mg QD
Levofloxacin 250 mg QD
QREC Spain 17% ’96
Garau J. AAC 1999;43:2736.
Treatment of Urethritis and Cervicitis
Gonorrhea
Female sex workers
BangladeshGCcervicitis
micro. success
Cipro susc. (62%) 97.5%
Cipro resist. (38%) 8.3 %
Rahman M. Clin Infect Dis
2001;32:884)
Chlamydia
Cefixime 400 mg
Ceftriax. 125/cefotax. 500 mg IM
Ciprofloxacin 500 mg*
Ofloxacin 400 mg*
Levofloxacin 250 mg*
Azithro 1 gram
Doxy 100 mg BID X 7 d
Widespread QRNG – SE Asia, India, Israel,others
Acute Cellulitis / Lymphangitis
 Staphylococcus aureus
Streptococcus pyogenes
 First-generation cephalosporins
Long acting - ceftriaxone
probenecid/cefazolin
azithromycin/linezolid
Kontiainen S. Eur J Clin Microbiol 1987;6 :420.
Canadian Study of Effect of Probenecid
on Cefazolin Concentrations
Cefazolin (ug/ml)
1000
Cefazolin +
Probenecid
(1 gr each)
100
Cefazolin
1gr alone
10
1
0
4
8
12
Hours
16
20
24
Brown G. J Antimicrob Chemother 1993;31:1009. Grayson ML. Clin Infect Dis 2002;34:1440.
Community-Associated MRSA

Methicillin-resistant Staphylococcus aureus

Also resistant to all penicillins/cephalosporins

Increasing proportion of staph isolates

30% of skin infections at Olive View-UCLA

Susceptible to clindamycin, quinolones,
TMP/SMX,rifampin, tetracylcne, vancomycin
Naimi TS. Clin Infect Dis 2001;33:990.
Take Home Points






Otitis- high-dose amoxicillin/Augmentin,
consider wait and see approach
CAP - scoring helps, guidelines work, quinolones very
effective, even as ICU monotherapy
UTI - short-course and TMP/SMX resistance
STDs - quinolone resistance in West, no cefixime,
consider flagyl for PID regimens
Infectious diarrhea - antibiotics work
CA-MRSA - biggest new problem