This is full detail about UTI for antibiotics use.

1. Intra-abdominal Infections
Resident’s Lecture
Edward L. Goodman, MD
May 1, 2006

2. Outline
• Pathogenesis of IAI
• Magnitude of problem
• Questions and Controversy
• Antimicrobial Regimens

3. Complicated Intra-Abdominal
Infections
Definition
Extends beyond the hollow
viscus of origin into the
peritoneal space
Associated either with
abscess formation or
peritonitis
Requires either operative or
percutaneous intervention to
resolve Solomkin J et al. Clin Infect Dis. 2003 Oct 15;37(8):997-1005.
Mazuski J et al. Surgical Infections. 2002. 3(3):161-173.
Medical Illustration Copyright © 2005
Nucleus Medical Art,
All rights reserved. www.nucleusinc.com

4. Complicated Intra-Abdominal
Infection Types
• Wide variety of
conditions
–Perforated
gastroduodenal ulcers
–Biliary tract infections
–Small bowel
perforations
–Complicated
appendicitis (with
abscess or perforation)
Goldstein E. Clin Infect Dis 2002 Sep 1;35(Suppl 1):S106-11.
Medical Illustration Copyright © 2005
Nucleus Medical Art,
All rights reserved. www.nucleusinc.com

5. Complicated Intra-Abdominal
Infections:Common Pathogens
Facultative and Aerobic Gram-
Negatives
Escherichia coli
Klebsiella spp
Pseudomonas
aeruginosa
Proteus spp
Enterobacter spp
other gram-negatives
71.3%
14.3%
14.1%
5.2%
5.1%
12.3%
Gram-Positive Organisms
Streptococcal spp
Enterococcus faecalis
Enterococcus faecium
Enterococcus spp
Staphylococcus aureus
38.0%
11.6%
3.4%
7.8%
3.5%
Solomkin J et al: Intra-abdominal infections. In: Schwartz SI, Shires GT, Spencer FC, et al: Principles of Surgery, 7th ed. New
York: McGraw-Hill Book Co., 1999:1541-42.
Anaerobic organisms
Bacteroides fragilis
other Bacteroides
Clostridia spp
Prevotella spp
Peptostreptococcus
spp Fusobacterium
spp Eubacterium spp
Others
34.5%
71.0%
29.2%
12.0%
16.7%
8.6%
16.5%
19.4%
Incidence of various bacteria
in 702 patients with intra-
abdominal infections

6. Pathogenesis
Weinstein, Onderdonk et al. JID 1975;132:282-286
• Animal models mimic clinical condition
– Gelatin capsules with rat feces implanted in peritoneal
cavity of rat
– Early peritonitis: 37% mortality
– Late abscesses in survivors: 100% incidence
• Antimicrobial Probes
– Gentamicin: acute mortality 4%; abscess in 98% of
survivors
– Clindamycin: acute mortality 35%; abscess in 5% of
survivors
– Combination: 7% mortality;6% abscess

7. Magnitude of Problem
Barie et al. Surg Infect 2004;5(4):365-73
• 465 patients 1991-2002 Major NYC Hosp
– Viscus perforation
– Peritonitis (78%) or abscess (22%)
– Community acquired 72%, Hospital Acquired
28%
• 74% organ dysfunction
• 23% mortality

8. Which Patients Require Therapeutic
Administration of ABX?
• Considered prophylactic and given <=24
hours
– Bowel injuries that are repaired within 12
hours
– Acute perforation of stomach, duodenum and
proximal jejunum in absence of antacid
therapy or malignancy (is there anyone not on Protonix®?)
– Acute appendicitis without gangrene,
perforation, abscess or peritonitis

9. Require ABX?
• Acute cholecystitis often not infected
– If infection strongly suspected
• Empiric therapy directed against enteric GNR
– Not necessary to cover enterococcus
– Not necessary to cover anaerobes unless biliary-bowel
anastamosis
• Infected pancreatic necrosis = colonic flora
– Prophylactic antibiotics for non infected
pancreatic necrosis are “controversial” (i.e., GI vs
ID)

10. Identification of High Risk Patients
(who need broader spectrum Rx)
• High risk of death/complications
– High APACHE II score
– Poor nutritional state
– Significant cardiovascular disease
– Inability to obtain source control
– Immunosuppressive therapy or condition
• Certain acute and chronic diseases
– e.,g, acute leukemia, dialysis
– Prolonged preop hospital stay
– Prolonged preop (>2 days) antimicrobials

11. Duration of Therapy
• Until resolution of clinical signs
– Normal temp and WBC (?CRP)
– Return of GI tract function
• If persisting clinical evidence of infection at
5-7 days
– Sono/CT
• If diagnostic, obtain source control by draining and
continue ABX and modify based on abscess
culture
• If negative for abscess, consider D/C ABX

12. When are Cultures Indicated?
• Uncomplicated, perforated or gangrenous appendix
without abscess: no impact on outcome when cultures
obtained
• Abscesses, peri-colonic infections: failure rates higher if
empiric ABX don’t cover aerobic flora
• Community epidemiology differs
• Anaerobic susceptibility:
– Unnecessary if predictably potent coverage with metronidazole,
carbapenems, beta lactam inhibitors used
• Resistance a concern with clindamycin, cefamycins, piperacillin
alone, most quinolones
– Indicated if persisting anaerobic isolates, bacteremias or
prolonged therapy indicated

13. Health Care Associated (HCA)
Infections (Nosocomial)
• Infections occurring after initial surgery are
HCA and may harbor resistant flora
• If empiric therapy does not include
coverage against subsequently recovered
resistant flora, morbidity higher
• Often require empiric combination therapy
– To cover MRSA, (VRE), MDR GNR

14. Complicated IA Infections
Infecting Flora by Onset Location
• Community-acquired infections
• Enteric GNB, facultative bacilli, and β-lactam-susceptible GPC,
obligate anaerobic bacilli (distal small-bowel and colon-derived
infections and for more proximal perforations when obstruction is
present)
– E coli, B fragilis
• Healthcare-associated infections (post-
op/nosocomial)
• Prolonged pre-op LOS or > 2 days pre-op antibiotics
• Usually more resistant flora
– Pseudomonas, Enterobacter and Proteus spp, MRSA, Enterococci,
and Candida spp
• Knowledge of local susceptibility patterns critical
Solomkin J et al. IDSA Guidelines Clin Infect Dis. 2003 Oct 15;37(8):997-1005.
GNB=gram-negative bacilli
GPC=gram-positive cocci
LOS=length of stay

15. What Should be Cultured?
• Blood cultures often no benefit in
community acquired IAI (CA-IAI)
• Intra-abdominal specimens
– Should be representative of the process
– Rarely need more than one or two
– Should always be sent for anaerobic as well
as routine
• Anaerobic transport system
• SWABS ARE NEVER APPROPRIATE

16. When Should Gram Stain be
Done?
• CA-IAI: not indicated
• HCA-IAI: indicated to help guide empiric
coverage
– If GPC clusters seen, cover for MRSA

17. Indication for Anti-fungal Rx
• Candida species isolated in 20% of acute
perforations of GI tract
• Anti-fungal therapy not indicated in most except:
– Recent immunosuppressive therapy
– Postop or recurrent IAI
• Choice of therapy
– C albicans – fluconzole
– Non albicans – caspofungin, voriconazole, AMB

18. Indications for Enterococcal
Coverage
• Not indicated for enterococci as part of
mixed flora in CA-IAI
– Numerous comparative trials have shown no
benefit from covering enterococcus
• Indicated in
– HCA-IAI
– Pure culture of enterococci
– Bacteremia with enterococci

19. Antimicrobial Regimens
• IDSA Practice Guidelines 2003
• Newer regimens
– Tigecycline CID 2006
– Moxifloxacin (FDA) 2005

20. Recommended Regimens:
2003 IDSA cIAI Guidelines
Adapted from Solomkin J et al. IDSA Guidelines. Clin Infect Dis. 2003 Oct 15;37(8):997-1005.
Mild-to-moderate
Infections
High-severity Infections
Single agent regimen
• Ampicillin/sulbactama
• Ticarcillin/clavulanic acid
• Ertapenem
• Piperacillin/tazobactam
• Imipenem/cilastatin
• Meropenem
Combination regimen
• Cefazolin or cefuroxime +
metronidazole
• Fluoroquinolone (FQ)-
based therapy +
metronidazole
• Cefotaxime, ceftriaxone,
ceftizoxime, ceftazidime,
cefepime + metronidazole
• Aztreonam + metronidazole
• FQ + metronidazole
a

21. Study
Moxifloxacin IV/PO vs. Piperacillin/Tazobactam
(PIP/TZO) IV  Amoxicillin/Clavulanate
(AMOX/CLA) PO
Design
Prospective, randomized, multi-center, multinational,
double-blind, active control, Phase III trials in patients
with complicated intra-abdominal infection (cIAI)
Comparator
Moxifloxacin 400 mg sequential IV/PO versus PIP/TAZ
3.375 gm IV q6h  AMOX/CL 800/114 mg PO q12h
Location
[years]
71 centers: in the US (62), Canada (7) and Israel (2);
[2000-2003]
Definition
cIAI
Requiring operative procedure or percutaneous
drainage. Purulence/ exudate, inflamed or necrotic
tissue confirmed at time of surgery.
Treatment 5-14 days
10
Outcome
Clinical response at test-of-cure (TOC) (-10%) 25-50
after entry into the study
Moxifloxacin Study Design
Data on File, Schering Corporation. Study #100272.
Malangoni M et al. ICAAC 2004. Washington DC. Abstract #L-990.

22. Moxifloxacin Study in cIAI
Patient Populations (N=681)
Population
Moxifloxacin
IV/PO
n (%)
PIP/TAZ IV
AMOX/CL PO
n (%)
Randomized 339 342
Safety 329 (97%) 327 (96%)
Efficacy Valid 183 (54%) 196 (57%)
Microbiologically
Evaluable Patients
(MBE)
150 (44%) 163 (48%)
Data on File, Schering Corporation. Study #100272.
Malangoni M et al. ICAAC 2004. Washington DC. Abstract #L-990.

23. 79.8
78.2
50
55
60
65
70
75
80
85
Moxifloxacin Study in cIAI
Clinical Response (TOC)†
Clinical
Response
(TOC)
(%
Patients)
n=153/196
n=146/183
Moxifloxacin IV/PO PIP/TZO IV
AMOX/CLA PO
p=NS; 95% Confidence Interval (-7.6, 9.2)
Efficacy-valid population
†Primary endpoint
Malangoni M et al. ICAAC 2004. Washington DC. Abstract #L-990.

24. 78.0 77.3
0
10
20
30
40
50
60
70
80
90
100
Microbiologic response includes eradication and presumed eradication at TOC in the
MBE population (N=313)
Bacteriological
Response
at
TOC
(%
Patients)
p=NS; 95% Confidence Interval (-9.9%, 8.7%).
Moxifloxacin IV/PO
117/150 126/163
n =
PIP/TZO IV
AMOX/CLA PO
Data on File, Schering Corporation. Study #100272.
Malangoni M et al. ICAAC 2004. Washington DC. Abstract #L-990.
Moxifloxacin
IV/PO
PIP/TZO IV
AMOX/CLA PO
Moxifloxacin Study in cIAI
Bacteriological Response

25. 77.0
85.4
76.7
72
0
10
20
30
40
50
60
70
80
90
Moxifloxacin Study in cIAI
Microbiologic Success
Micro
Success
(TOC)
(%
Patients)
69/90
67/87 36/50
35/41
E coli B fragilis
Microbiologic success includes eradication and presumed eradication at TOC in the
MBE population (N=313)
n =
Data on File, Schering Corporation. Study #100272.
Malangoni M et al. ICAAC 2004. Washington DC. Abstract #L-990.
Moxifloxacin
IV/PO
PIP/TZO IV
AMOX/CLA PO
p=NS

26. Adverse Event
Moxifloxacin
(N=329)
n (%)
PIP/TZO IV
AMOX/CLA PO
(N=327)
n (%)
Any treatment-emergent adverse event
(AE)
276 (83.9) 271 (82.9)
Died 6 (1.8) 7 (2.1)
Serious AE 63 (19.1) 66 (20.2)
Premature discontinuation due to AE 34 (10.3) 28 (8.6)
Any drug-related adverse AE (≥2%) 82 (24.9) 90 (27.5)
Diarrhea 16 (5) 26 (8)
Nausea 16 (5) 13 (4)
Gamma glutamyl transferase
increase
8 (2) 5 (2)
Data on File, Schering Corporation. Study #100272.
Malangoni M et al. ICAAC 2004. Washington DC. Abstract #L-990.
Safety Population
Moxifloxacin Study in cIAI
Overall Safety Profile

27. Tigecycline for Complicated IAI
• Pooled date from 2 phase 3 studies
comparing Tigecycline to Imipenem-
cilastatin in 1642 adults

31. Caveats on Newer Regimens
• Moxifloxacin
– Anaerobic resistance to FQ may emerge
– Limited experience
– Nothing published yet
• Tigecycline
– Nausea/vomiting limiting factor in our
experience
– Literature: 44%

32. 2003 IDSA cIAI Guidelines
Overall Antimicrobial Management
• Fluid resuscitation required prior to initiating antibiotic to
restore adequate visceral perfusion and ensure drug
distribution
• Empirical coverage initiated upon suspicion of cIAI
• Duration of therapy should be continued until resolution of
clinical signs of infection:
– Afebrile
– Normalization of WBC count
– Return of gastrointestinal function
• If infection persists beyond 5-7 days:
– Diagnostic investigation required (CT or ultrasound) and/or
additional intervention for source control
– Ensure treatment regimen provides appropriate coverage
Solomkin J et al. IDSA Guidelines Clin Infect Dis. 2003 Oct 15;37(8):997-1005.

33. Bibliography
• Babinchak T, Ellis-Grosse E et al. The Efficacy
and Safety of Tigecycline for the Treatment of
Complicated Intra-Abdominal Infections:
Analysis of Pooled Clinical Trial Data. Clin Inf
Dis 2005;41 (Suppl 5):S354-67
• Barie PS, Hydo LJ, Eachempati. Longitudinal
Outcomes of Intra-Abdominal Infection
Complicated by Critical Illness. Surg Infect
2004;5(4):365-73
• Goldstein EJC. Intra-Abdominal Anaerobic
Infections. Clin Inf Dis 2002;35(Suppl ):S106-11

34. Bibliography
• Schering-Plough Company Data on File
(personal communication)
• Solomkin JS, Mazuski JE, Baron EJ et al.
Guidelines for the Selection of Anti-Infective
Agents for Complicated Intra-abdominal
Infections. Clin Infect Dis 2003;37:997-1005
Access on ID Society.org. Practice Guidelines
• Weinstein WM, Onderdonk AB, Bartlett JG,
Louie TJ, Gorbach SL. Antimicrobial therapy of
experimental intraabdominal sepsis. J Infect Dis
1975;132:282-6