Control of Antibiotic Resistance

1
(No Transcript)
2
(No Transcript)
3
(No Transcript)
4
(No Transcript)
5
(No Transcript)
6

• Extended Spectrum Cephalosporins (3rd Gen)

Inactivated by
Extended Spectrum Beta-Lactamase (ESBL)
7

• Carbapenems
• Imipenem, Meropenem

Inactivated by
Carbapenemase (KPC Klebsiella pneumoniae
Carbapenemase)
8
(No Transcript)
9
Blood Cult Sensi FinalKlebsiella pneumoniae
IN AEROBIC BOTTLE
10
CR-Klebsiella (ESBL)
Year
11

• Therapy of Multiresistant KPC Producing
  Klebsiella Infections

12

• What is the answer?
• In that case,
• what is the question?

Gertrude Stein
13
Treatment

• What drugs are avaiable for MDR Klebsiella
  isolates?
• Carbapenems
• Tigecycline (doxycycline)
• Gentamicin
• Polymyxins (B and E)

14
Treatment

• Carbapenem questions
• Relative potency/ toxicity of doripenem
• Daily dose, interval, infusion rate, emergent
  ACT-1/ D2 porin resistance

15
Treatment

• Tigecycline questions
• Daily dose/ toxicity
• Serum/ tissue levels
• Emergent resistance

16
Treatment

• Gentamicin questions
• Maximum single daily dose/ toxicity
• Possible amikacin activity

17
Treatment

• Polymyxin questions
• Polymyxin B vs colistin (Polymyxin E)
• Daily dose/ toxicity
• Serum/ tissue levels
• Emergent resistance

18
Treatment

• Aerosolized therapy?

19
Treatment

• Combination Therapy?
• Mechanisms
• Two or three drugs
• Activity of Each drug
• Synergistic or additive or neither
• Rifampin plus

20

• All patients had deep seated infections with
  septicemia (septic thrombophlebitis, prostatitis,
  pneumonia, etc)

Ostenson AAC 197712655-659
21
(No Transcript)
22
Zuravleff, J. Lab Clin Med June 1983
23
Rifampin added to antipseudomonal B-lactam agent
and an aminoglycoside in patients with
Pseudomonas aeruginosa bacteremia

• Multicenter, prospective randomized trial
• Zelen protocol used consent was only obtained
  from patients randomized to experimental therapy
  (rifampin arm). Patients who declined rifampin
  arm were placed on standard therapy (in spite of
  randomization)
• Results
• 121 consecutive hospitalized patients with
  Pseudomonas aeruginosa bacteremia were enrolled
• Entry stratified for prior use of empiric
  antipseudomonal antibiotics, neutropenia,
  severity of illness, and presence of pneumonia
• 58 patients enrolled in rifampin arm
• Bacteriologic cure much higher in rifampin arm
• Breakthrough or relapse of bacteremia occurred in
  2 rifampin arm vs 14 of standard arm
• But no survival differences

Korvick AAC 199236620-625
24
In vitro synergy study with polymyxin B or
rifampin in combination with other agents in GNRs

• In vitro synergy of polymyxin B with imipenem,
  rifampin, ceftazidime, ciprofloxacin in
  Acinetobacter baumanii, Klebsiella pneumoniae,
  Pseudomonas aeruginosa
• Checkerboard agar dilution and time-kill tests in
  122 clinical isolates
• Significant improved in vitro susceptibility and
  time-kill with imipenem-polymyxin B or
  rifampin-polymyxin B in Acinetobacter and
  Klebsiella sp.

Chin NX, Scully B, Della-Latta P 38th ICAAC 1998,
Abs E56
25
Yoon, AAC, 200448p753-757
26
(No Transcript)
27
Klebsiella pneumoniae
E- test M.I.C.
28
(No Transcript)
29
(No Transcript)
30
(No Transcript)
31
(No Transcript)
32
Isolate Klebsiella pneumoniae (KPC) Patient ID
3183 Age/Sex 86 M Unit 5N Source
Blood Collected 01/12/09
33
(No Transcript)
34
(No Transcript)
35
(No Transcript)
36
(No Transcript)
37
(No Transcript)
38
(No Transcript)
39
(No Transcript)
40
Summary

• MDR Klebsiella has created a hospital, city, and
  state-wide hospital associated epidemic.
• Isolates are possibly susceptible to gentamicin,
  tigecycline and polymyxin.
• The number of such infections at NYHQ has tripled
  since 2003. Bacteremias have more than
  quadrupled.

41
Summary contd

• This is due primarily to imipenem/meropenem
  resistance caused by a new enzyme (KPC).
• Infection due to imipenem resistant Pseudomonas
  and Acinetobacter has remained stable or
  decreased during this period.

42
Control Methods

• 1-3. Handwashing, handwashing, and
• handwashing.
• Soap and water for both Klebsiella and C.diff.
• Alcohol based lotion, but NOT for C.diff.
• Isolation
• Gloves PLUS handwashing.
• Gowns on close contact.

43
Control Methods contd

• Segregation
• A new segregated Oncology Unit for neutropenic
  patients.
• Segregation of colonized, infected or high risk
  patients into specific areas throughout the
  hospital (particularly those from nursing homes).
• Creation of clean areas.

44
Control Methods contd

• Potential initial empiric antibiotic therapy for
  febrile neutropenia or nosocomial septic shock
• tigecycline rifampin meropenem polymyxin
  or gentamicin.
• Remove Foley catheters whenever possible.
• Polymyxin-bacitracin ointment or powder
  (Polysporin) to colonized or infected wounds/
  decubiti.

45

• There aint no answer.
• There aint gonna be any answer.
• There never has been an answer. Thats the answer.

Gertrude Stein
46
(No Transcript)
47
(No Transcript)