# Presentation: 399874

## Detecting Resistance in Gram-Negative Bacteria, Including ESBL Issues!

**Janet Fick Hindler, MCLS MT(ASCP)***
**UCLA Medical Center**
**Los Angeles, CA**
**jhindler@ucla.edu**
*** ***

****also working as a consultant with the Association of Public Health Laboratories with support from CDC***

## At the conclusion of this talk, as related to gram-negative bacteria, you will be able to......

**Discuss ****reliable methods**** for detecting resistance among commonly encountered species.**
**Explain how to implement current ****CLSI ****antimicrobial susceptibility testing and reporting recommendations.**
**List results obtained from testing patient’s isolates that should be ****verified**** prior to reporting as part of ****quality assessment.****  **

## -Lactamases in GNR

- B-lactamases

## Evolution of -Lactamases

**Ampicillin**

**1965**

**TEM-1**
***E.coli***
***S.paratyphi***

**1970s**

**TEM-1**
**Reported in **
**28 Gm(-) sp**

**1983**

**ESBL in **
**Europe**

**1988**

**ESBL **
**in USA**

**2000**

**> 130 ESBLs**
**Worldwide**

**Extended-spectrum**
**Cephalosporins**

**1963**

**Evolution of ********-Lactamases**

**Notes:**
This slide presents the evolution/historical development of the classical plasmid-mediated TEM and SHV -lactamases to extended-spectrum -lactamases.  Over a 35 year time period, the transformation has been remarkable. 

## -Lactamases

**TEM-1 ********-lactamase ****(coded by *****bla*****TEM-1**** gene)**
**amp-R**** in *****E. coli***
**amp-R**** in *****H. influenzae***
**pen-R**** in GC**
**SHV-1 ********-lactamase ****(coded by *****bla*****SHV-1**** gene)**
**amp-R**** in *****K. pneumoniae***** **
***bla*****TEM-1 ****and *****bla*****SHV-1**** mutate  and resultant genes code for ESBLs**

## Definitions

**Narrow-spectrum ********-lactam agents**
**Active against G- or G+ bacteria only; e.g.,  penicillin **
**Broad-spectrum ********-lactam agents**
**Active against G- and G+ bacteria; e.g., ampicillin, 1****st**** generation cephalosporins **

## Definitions (con’t)

**Extended-spectrum ß-lactam agents**
**Enhanced activity against G- and some G+ bacteria; e.g., 3****rd**** and 4****th**** generation cephalosporins, carboxy- and ureidopenicillins**
**Extended-spectrum ß-lactamases (ESBLs)**
**Enzymes produced by GNR that destroy certain extended-spectrum ß-lactam agents, including ****3****rd**** generation cephalosporins**

## Check for routine methods for GNR

**www.phppo.cdc.gov/dls/master/default.asp**

**Visit this site and order “FREE”: CD ROM**

**Check for routine methods for GNR**

## Slide 9

## Enterobacteriaceae

**Extended-spectrum ********-lactamases (ESBLs)**
**AmpC ********-lactamases**
**Salmonella/Shigella**

## Enterobacteriaceae  First Choice Therapy 

***Klebsiella***
***Enterobacter***

**   **
**3****rd**** gen cephalosporin**
**fluoroquinolone**
**ertapenem, imipenem **
**   ****meropenem**
**ertapenem, imipenem **
**   ****meropenem**
**extended-spectrum penicillin + aminoglycoside**

**Sanford, 2004**

## Why is important to do special tests and follow complex reporting rules for ESBLs?

**In vitro tests may be ****misleading**** (e.g., may see “S” in vitro but drug may not work!)**
**Many types of ESBLs with varying susceptibility profiles ****(TEM ******** 130; SHV ******** 50; CTX-M ******** 30)**
**Treatment failures**** (esp. bacteremia) when patient treated with 3rd generation cephalosporins**
**ESBL-producing isolates can cause ****nosocomial outbreaks**

## Outcome of Serious ESBL Infections When Treated with 3rd gen Cephalosporin 

| MIC (μg/ml)
3rd gen cef | Failure | Died within 14 d of bacteremia |
| --- | --- | --- |
| 8 S | 100% (6/6) | 33% (2/6) |
| 4 S | 67% (2/3) | 0 (0/3) |
| 2 S | 33% (1/3) | 0 (0/3) |
| ≤1 S | 27% (3/11) | 18% (2/11) |
| Total | 54% (15/28) |  |

**Paterson et.al. 2001. JCM.39:2206-12**

## ESBL Testing	

**Organisms:*****	******	******	******	******	******	******	******        E. coli, Klebsiella***** spp., *****Proteus mirabilis***
**Screen test:****	****	****	****	****	****	**** Decreased susceptibility to extended-spectrum ß-lactams**
**Phenotypic confirmatory test:****	****	****	****       ß-lactam activity restored by ß-lactamase inhibitor (i.e. clavulanic acid)**

**CLSI M100-S15 Table 2A (M2, M7)**

## Proteus mirabilis and ESBLs

**Not necessary to test routinely**
**Uncommon in USA**
**Significant problems in some locations (e.g., Europe, South America)**

## ESBL Reporting Rule

**The rule ****(CLSI M100-S15)...**** **
**“****Strains of *****Klebsiella***** spp. *****E. coli, *****and***** Proteus mirabilis***** that produce ESBLs may be clinically resistant to therapy with penicillins, cephalosporins, or aztreonam, despite apparent in vitro susceptibility to some of these agents.”**
**The message...**
**Report “confirmed” ESBL-producing strains as R to all ****penicillins, cephalosporins, ****and**** aztreonam**** **

## ß-lactams Edited to ”R”

**Penicillins**
**e.g., ampicillin, carbenicillin, mezlocillin, piperacillin, ticarcillin**
**Cephalosporins**
**e.g., cephalothin, cefamandole, cefuroxime, cefotaxime, ceftriaxone, ceftazidime, cefepime**
**Monobactam**
**aztreonam**

## ß-lactams NOT Edited to ”R” re: CLSI Reporting Rules

**Cephamycins**
**e.g., cefoxitin, cefotetan, cefmetazole**
******-lactam inhibitor combinations**** **
**e.g., piperacillin-tazobactam **

##  ESBL Screening Test

**	****	****	****        ****Disk zone (mm)    MIC (μg/ml)**_** **_
***Cefpodoxime****	****	**** ********17     ****	****	**** >4****
***Ceftazidime****	****	**** ********22  ****	****          >1**
***Cefotaxime****	****	**** ********27  ****	****          >1**
** ****Ceftriaxone****	****	**** ********25  ****	****          >1**
** ****Aztreonam****	****	**** ********27  ****	****          >1**

**CLSI  M100-S15 Table 2A (M2, M7)**

*** only these drugs appropriate for *****P. mirabilis***
****>1 ********g/ml for *****P. mirabilis***** **

## Klebsiella pneumoniae   ?ESBL (cefpodoxime = 16 μg/ml)

**cefoxitin****	****         1 S **
**ciprofloxacin  ****	****      0.5 S**
**imipenem                 ******** 0.25 S**
**pip-tazo    ****	****	****   8 S**
**am, cfaz, gm, T-S            R**
**    *****hold cefepime, cefotaxime if ****“S”**

_**MIC (μg/ml)**_

**“****This *****K. pneumoniae***** is suspicious for extended-spectrum beta-lactamase (ESBL) production; confirmatory tests pending”**

**PRELIM:**

**Ucla example**

## ESBL Phenotypic Confirmatory Test

**Test:****	**
**cefotaxime**
**cefotaxime/clavulanic acid**
**ceftazidime**
**ceftazidime/clavulanic acid  **
**Results:**
**clavulanic acid restores activity of cefotaxime or ceftazidime or both**
**QC**** **
***E. coli***** ATCC 25922; *****K. pneumoniae***** ATCC 700603**

**CLSI  M100-S15 Table 2A (M2, M7)**

## ESBL Confirmatory Test

**ESBL Confirmatory Test**
**Positive**** for ESBL**

**Ceftaz/CA**

**Cefotax/CA**

**Ceftaz**

**Cefotax**

## ESBL Confirmatory Test

**Ceftaz/CA**

**Ceftaz**

**Etest**

**MicroScan – ESBL panel**
**Vitek – confirmatory test **
**Vitek 2 - Advanced Expert**

## Klebsiella pneumoniae   ESBL

**cefepime****	****	****  2 S R**
**cefoxitin****	****           1 S**
**cefotaxime****	****	****  1 S R **
**ciprofloxacin****	****         0.5 S**
**imipenem****	****       0.25 S**
**pip-tazo****	****	****      8 S****	**
**am, cefaz, gent, T-S                R   **
** **

_**MIC (μg/ml)**_

**“****Confirmatory tests for this *****K. pneumoniae***** indicate unusual resistance [extended-spectrum beta-lactamase (ESBL) production]; ID consult suggested”**

**FINAL:**

**Ucla example**

## ESBL Confirmatory Test Negative for ESBL 

**Ceftaz/CA**

**Cefotax/CA**

**Ceftaz**

**Cefotax**

## E. coli - probable AmpC (plasmid-mediated)

**	****	****ampicillin****	****     > 32 R**
**	****	****cefazolin****	****     > 32 R**
**	****	****cefotaxime                  > 32 R**
**	****	****cefoxitin****	****	****    > 32 R**
**	****	****cefepime****	****	****         8 S**
**	****	****ciprofloxacin       ****	****       0.5 S**
**	****	****imipenem                 ******** 0.25 S**
**	****	****pip/tazo****	****      128 R**

_**MIC (μg/ml)**_

**“****Confirmatory tests for *****E. coli***** indicate unusual resistance (but NOT due to ESBLs)”**

**Ucla example**

## If ESBL screen test is positive, must we do the confirmatory test prior to reporting isolate as an ESBL? 

**Yes**** - unless you are confident that the isolate ****is / is not an ESBL**** producer based on:**
**A previous isolate from the patient **
**An endemic strain in your institution**

## What about testing / reporting for ESBLs on urine isolates?

**The suggestion ****(CLSI M100-S15)...**
**“****The decision to perform ESBL screening tests on ****all urine isolates**** should be made on an institutional basis.”**
**Rationale...**
******-lactam concentration in bladder is very high and overcomes hydrolysis by ESBL enzymes**
**The concerns...**
**Identifying urine from acute cystitis vs. other **
**Patient with isolate from urine + other sites**
**Infection control issues**

## Will CLSI confirmatory test detect ALL ESBL-producing GNR?

**No ****- some isolates have ****ESBLs plus**** ****other resistance mechanisms**** that mask ESBL detection in the confirmatory test, e.g.,  **
**> 1 ESBL**
**ESBL + ampC**
**ESBL + porin mutation **
**ESBLs occur in ****species**** other than *****E. coli, Klebsiella***** spp., and *****Proteus mirabilis***** which CLSI does not currently address**

##  Current CLSI Efforts Re: ESBLs

**Determine ****“best way”**** to detect isolates with all different types of ESBLs or other ********-lactam resistance mechanisms**
**Cephalosporin and penicillin ****breakpoints**** **_**MAY**_** be lowered **
**Example: cefotaxime**
**Current – Susceptible at ******** 8 ********g/ml**
**Proposed – Susceptible at ******** 1 or ******** 2 ********g/ml**

## UCLA Inpatient Non-urineIsolates (2000-2004)

| 
Organism | 
N | Ceftazidime-R (often used as a marker for ESBL) | ESBL test positive
 |
| --- | --- | --- | --- |
| E. coli | 804 | 79 (9.8%*)  | 35 (4.3%)
  |
| Klebsiella pneumoniae | 555 | 78 (14.1%)
  | 70 (12.6%) |

***% of total tested**

## ESBL Testing E. coli and Klebsiella spp. Strategy 

**Perform ****screen**** test (especially isolates from normally sterile sites)**
**Perform ****confirmatory**** test or send to reference lab**
***    ******(P. mirabilis***** – perform screen and confirmatory test on isolates from sterile sites)**

## Amp C -Lactamases

**Amp C ********-Lactamases**

**Induction of AmpC **
******-lactamase production**

**Selection of**
**Amp-C producing Resistant mutants**

***amp*****C gene codes for ampC ********-lactamase!**

## What is meant by induction of AmpC -lactamase?

**Exposure of organism to**** ********-lactam (inducer) ****stimulates production of AmpC ********-lactamase**
**Bug does not waste energy to produce AmpC ********-lactamase unless it is in danger of being killed by ********-lactam!**
**AmpC gene usually on chromosome**
**Characteristic of certain genera and species**
**Reversible**

## Should we do any special testing for inducible ß-lactamases?

**No,**** since induction is an ****in vitro phenomenon**** with no clinical impact unless therapy is with the unlikely combination of strong inducer with a 3****rd**** generation cephalosporin.**

## -Lactamase Induction Potential

**cephamycins**
**carbapenems**
**clavulanic acid**
**cephalothin**
**sulbactam**
**tazobactam**
**aztreonam**
**3****rd**** an 4****th**** gen cefs**

**high**

**low**

## ß-Lactamase Induction

**ß-Lactamase Induction**
***E. cloacae***

**Cefoxitin -**
**inducer**

**Cefotaxime -**
**3****rd**** gen cef**

## Organisms that Produce Inducible AmpC ß-Lactamases

***Acinetobacter baumannii***
***Citrobacter freundii***
***Enterobacter***** sp.**
***Morganella morganii***
***Providencia***** sp.**
***Pseudomonas aeruginosa***
***Serratia marcescens***
***Stenotrophomonas maltophilia***
***Others***

## E. coli and Klebsiella sp. are not on the list, so why do we talk about AmpC in these species?

**AmpC ********-lactamase**** is produced in minimal amounts in *****E. coli***** and *****Klebsiella***** spp. and is ****not**** inducible; sometimes there is slight increased production which results in...**
** ****R to ampicillin and 1****st**** generation cephalosporins**
***AmpC***** ****gene**** can be transferred to plasmid and ********-lactamase can be hyperproduced **
**resistant to 3****rd**** gen cefs, cephamycins, aztreonam, usually carboxy- and ureidopenicillins**

## What is meant by selection of resistant mutants (derepression)?

**Chromosomal *****amp*****C gene**** spontaneously mutates**
_**Independent of antibiotic exposure**_
**Can occur ****in vitro and in vivo****; irreversible**
**Resistant mutants:**
**occur at a frequency of 1 in 10****-6**** to 10****-8 ****cells**
**continuously produce large amounts of ampC ß-lactamase**
**resistant to 3****rd**** gen cefs, aztreonam, usually carboxy- and ureidopenicillins**

## What is meant by selection of resistant mutants (derepression)? (con’t)

**Resistant mutants are ****selected out**** if they are exposed to antimicrobial agents to which they are resistant**
**Frequency of selection of resistant mutants varies by species**
***Enterobacter***** spp. – high**
***Serratia***** spp. – low**
**Resistant mutant ****continuously**** produces ampC ********-lactamase**

## Should we do any special testing for ß-lactam-resistant mutants?

**No,**** physicians should be educated that use of 3****rd**** generation cephalosporins (and aztreonam and usually carboxy- and ureidopenicillins) can select out resistant mutants**
**If many resistant mutants are present in the specimen, they ****should test resistant**** **
**Follow CLSI rule for ****“retesting”**** to see if resistance has “emerged” in a previously susceptible isolate**
**Consider adding comment to report **

## CLSI Retesting Rule

**“****Resistance may develop in 3-4 days for..... *****Enterobacter, Citrobacter, Serratia***** with ****3rd generation cephalosporins****, *****P. aeruginosa***** with ****all drugs****”**

**CLSI M2-A8, M7-A6**

## Some believe 3rd gen cephalosporins should not be used for Enterobacter, Citrobacter, Serratia, so what are reporting options when these isolates are “S” to 3rd  gen cephalosporins ?

**Report ****“S” for 3****rd**** gen cefs**** without comment**
**Edit “S” to ****“R” for**** ****3****rd**** gen cefs**
**Add ****comment**** such as “Due to high likelihood of selecting resistant mutants, 3****rd**** gen cefs may not be effective for *****E. cloacae***** despite a susceptible result in vitro”**
**Add ****other type of comment??**

## Enterobacter cloacae

**ampicillin****	****R**
**cefazolin****	****R**
**cefotaxime****	****S**
**gentamicin****	****S**
**Imipenem****	****S**
**piper-tazo****	****S**

**“****Combination therapy (e.g. ********-lactam + aminoglycoside)**** ****should be considered for *****Enterobacter cloacae*****”**

**Ucla example**

## cefotaxime

**cefotaxime**

**Initial culture – day 1**

## cefotaxime

**cefotaxime**

**CTX**
** ****30**

**Followup culture – day 3**

## Salmonella / Shigella

*Salm / Shig*

## Salmonella / Shigella

**“****For fecal isolates of *****Salmonella***** and *****Shigella***** spp****., only ampicillin, a fluoroquinolone, and trimethoprim-sulfamethoxazole should be tested and reported routinely.  In addition, chloramphenicol and a 3****rd****-generation cephalosporin should be tested and reported for extraintestinal isolates of *****Salmonella***** spp****.”**

**CLSI M100-S15 Table 2A (M2, M7)**

## Specimen:	stoolResults:	Shigella spp. 

**ampicillin****	****R**
**ciprofloxacin****	****S***
**trimeth-sulfa****	****R**
**cefixime****	****S****
**ceftriaxone****	****S**
**	****	**

*******Not for children**
****Oral agent; broad-spectrum cephalosporin**

## Salmonella and Fluoroquinolones (FQ)

**“****FQ-susceptible strains of Salmonella that test resistant to ****nalidixic acid**** may be associated with clinical failure or delayed response in FQ-treated patients with extraintestinal salmonellosis. Extraintestinal isolates of Salmonella should also be tested for resistance to ****nalidixic acid.****  For isolates that test susceptible to FQs and resistant to ****nalidixic acid****, the physician should be informed that the isolate may not be eradicated by FQ treatment. A consultation with an infectious disease practitioner is recommended.”**

**CLSI M100-S15 Table 2A (M2, M7)**

## Salmonella spp. (blood)

**	****	****ampicillin****	****>32 R****	****	****ceftriaxone****	********0.5 S****	****	****ciprofloxacin****	**** ********0.25 S ****	****trimeth-sulfa****	****>4/78 R**

***...******.Test nalidixic acid on extraintestinal isolates of Salmonella that are “S” to ciprofloxacin******  ***

_**MIC (**__****__**g/ml)**_

## Salmonella and Ciprofloxacin

**      ******** ****0.06 ****	****      S ****	****       ****	****    none ****	****	**** S**
**      ****0.12- 1  ****	****      S****	****	****     one****	****	**** R***
**	****	****   ****2****	****	****       I****	****	****	****one or two****	**** R**
**        ******** ****4****	****	****      R****	****	****     two****	****	**** R**

**CIP**** ****MIC****	****       CLSI                Likely      Nalidixic **
**(********g/ml)     Interpretation      Mutation       acid**

***Some patients with extraintestinal infection with *****Salmonella *****spp.***** *****may fail FQ therapy; u****se nalidixic acid as a surrogate to detect single step mutants.**

## Salmonella spp. (blood)

**	****	****	****ampicillin****	****	****   >32 R****	****	****	****	****ceftriaxone****	****	****  ********0.5 S****	****	****	****	****ciprofloxacin       ********0.25 S*****	****	****	****	****trimeth-sulfa****	****>4/78 R**

****....if nalidixic acid is resistant, add comment such as...... ***
**”****This isolate has reduced susceptibility to fluoroquinolones and patient may not respond to fluoroquinolone treatment.  ID consult suggested.”**

_**MIC (**__****__**g/ml)**_

**Ucla example**

## Salmonella/Shigella Strategy 

**Fecal isolates**
**Report ampicillin, ciprofloxacin, trimethoprim-sulfamethoxazole only **
**For Salmonella, test ****fecal isolates**** when requested; if Salmonella patient asymptomatic or illness mild, antimicrobial therapy often not indicated**
**Test nalidixic acid on ****blood (extraintestinal) isolates**** of *****Salmonella***** spp. that are ciprofloxacin-S **

## Pseudomonas aeruginosaNon-Enterobacteriaceae

*P. aeruginosa*

## CLSI Table 1M100-S15

**M2, disk diffusion**

**M7, MIC testing**

**CLSI Table 1****M100-S15**

## CLSI Table 1M100-S15

**M2, disk diffusion**

**M7, MIC chart similar but more drugs**

## CLSI Table 1 M100-S15   M7, MIC 

***Pseudomonas aeruginosa***** and**
**Other***** Non-Enterobacteriaceae *****j**_ _

**j** **Include......**
***Pseudomonas spp.***
**Nonfastidious glucose-nonfermenting GNB**
**except......**

***Acinetobacter***** **
**spp.**

***Burkholderia ***
***cepacia***

***Stenotrophomonas maltophilia***

## Pseudomonas aeruginosa and Other Non-Enterobacteriaceae

**The following may be indicated for **_**(routine)**_** testing of ****some *****Pseudomonas***** spp.**** and other nonfastidious, glucose-nonfermenting, gram-negative bacilli ****(not *****P. aeruginosa*****)**
**Ticarcillin-clavulanic acid**
**Trimethoprim-sulfamethoxazole**
**Cefotaxime or ceftriaxone**
**Chloramphenicol**
**Ceftizoxime - urine isolates only**
**Tetracycline - urine isolates only**

**CLSI M100-S15 Table 1 (M7)**

## Pseudomonas aeruginosa

| First Choice Drugs |
| --- |
| ticarcillin, piperacillin, ceftazidime,
cefepime, imipenem, meropenem
tobramycin, ciprofloxacin, aztreonam    |

******-lactam as above + tobramycin or ciprofloxacin for serious infections**
**For UTI, single drug usually effective**

**Sanford, 2004**

## Rx: Comment Non-Enterobacteriaceae

**“*****Rx:***** *****P. aeruginosa***** infections in granulo-cytopenic patients and serious infections in other patients should be treated with maximum doses of the selected antipseudomonal penicillin (carboxypenicillin or ureidopenicilllin) or ceftazidime in combination with an aminoglycoside.” **

**CLSI M100-S15 Table 2B (M2, M7)**

## Pseudomonas aeruginosa

**	****	****ceftazidime ****	****S**
**	****	****ciprofloxacin****	****S**
**	****	****gentamicin ****	****S**
**	****	****piperacillin ****	****S**
**“****Combination therapy with a beta-lactam and an aminoglycoside should be considered”**

**Ucla example**

## Acinetobacter baumannii

**First Choice Drug**
**Imipenem or        ****	****        meropenem**
**Fluoroquinolone + amikacin or ceftazidime****	****	****	**

**    ****Alternative Drugs**
**  ****ampicillin-sulbactam**

**Sanford, 2004**

## Acinetobacter baumannii

**amik, gent, tob****	****	****R**
**ampicillin-sulbactam****	****	****R**
**cefepime****	****	****R****	****	**
**ceftazidime ****	****	****R**
**doxycycline****	****  R**
**ciprofloxacin****	****	****R**
**imipenem****	****	****R**
**piper-tazobactam ****	****  R**
**trimeth-sulfa****	****  R**
** **

**Do more?**

## What should we do when all are “R”?

**Consult with MD**
**Is isolate important to patient management?**
**Suggest ID consult**
**Other drugs**** to test?**
**Use reference lab**
**Colistin / polymyxin B??**
**“****CF Referral Center**** for Susceptibility and Synergy Testing” ****	****	**** ****	****	****	****http://synergy.columbia.edu/**

## Testing Colistin / Polymyxin B

**MIC and disk diffusion ****QC ranges for both**** **
**MIC breakpoints**** for polymyxin B only**
**“****Polymyxin B MIC result can predict colistin MIC”**
**S ********2 ****μ****g/ml      R ********4 ****μ****g/ml**
**Can report polymyxin B MIC with comment re: colistin**
**Further work needed on**** disk diffusion**
**Disk diffusion**** failed to identify some R isolates (primarily *****S. maltophilia***** and *****Acinetobacter***** spp.); Gales et al. 2001. J JCM. 39:183-190**
**Rare resistance in *****P. aeruginosa***

## Acinetobacter baumannii

**amik, gent, tob****	****	****R**
**ampicillin-sulbactam****	****	****R**
**cefepime****	****	****R****	****	**
**ceftazidime ****	****	****R**
**doxycycline****	****  R**
**ciprofloxacin****	****	****R**
**imipenem****	****	****R**
**piper-tazobactam ****	****  R**
**polymyxin B                      ******** 2 ********g/ml S**
**trimeth-sulfa****	****  R**
** **

**Polymyxin B “S” *****A. baumannii***** are colistin “S”**

## Stenotrophomomas maltophilia

**First Choice Drug**
**   ****trimeth-sulfa****	****	**

**Alternative Drugs**
**  ****ticarcillin-clav or aztreonam + ticarcillin-clav**
**   ****minocycline ceftazidime**
**  **

**Sanford, 2004**

## S. maltophilia (blood)

**ceftazidime****	**** 32   R**
**minocycline****	****   1   S**
**imipenem****	****     ****R**
**ticar-clav****	**** 16   S**
**trimeth-sulfa                0.5/9.5 S**

**“****If ****trimethoprim-sulfamethoxazole**** not an option, ID consult suggested”**

_**MIC (**__****__**g/ml)**_

****S. maltophilia***** is typically resistant to imipenem; **
**report to educate MDs that imipenem is not for this species**

**Ucla example**

## The dilemma of colonization vs. infection... 

***Acinetobacter baumannii***** **
**Isolates from variety of sources  for 59 patients  **
**18 with documented infections**
**	****Go, Urban, Burns, Kreiswirth et al. 1994. Lancet 12:1329****.**
***Stenotrophomonas maltophilia***
**Respiratory isolates:**
**	****29 - 47% = infection**
**	****	**** ****Khardori et. al. 1991. RID. 12:997**
**	****	**** ****Laing et al. 1995. JCM. 33:513**
**	****	**** ****Villarino et al. 1992. Infect Cont Hosp Epidem. 13:201**

## Sputum Culture Report Option

**GS:**
**	****Many oral flora****	**
**Culture:**
**	****Few *****Acinetobacter baumannii***
**	****Normal oral flora**

## Sputum Culture Report Option

**GS:**
**	****Many oral flora**
**	****Few WBCs**
**	****Moderate GNR**
**Culture:**
**	****Many *****Acinetobacter baumannii***
**	****Many Normal oral flora**

**“****Susceptibilities for *****A. baumannii  *****are not routinely done because *****A. baumannii***** is frequently a colonizer when isolated from non-sterile body sites (e.g. respiratory).  If *****A. baumannii***** is causing infection, susceptibility test results should guide therapy.  Please contact laboratory”**

**Ucla example**

## Sputum Culture Report Option

**GS:**
**	****Many oral flora**
**	****Few WBCs**
**	****Moderate GNR**
**Culture:**
**	****Many *****Stenotrophomonas maltophilia***
**	****Many Normal oral flora**

**“****Susceptibilities for *****Stenotrophomonas maltophilia *****are not routinely done because *****S. maltophilia***** is frequently a colonizer when isolated from non-sterile body sites (e.g. respiratory).  If *****S*****. *****maltophilia***** is causing infection, trimethoprim-sulfamethoxazole is the drug of choice”**

**Ucla example**

## Pseudomonas aeruginosa and Other non-EnterobacteriaceaeStrategy

**Test ****appropriate drugs**** on routine panel**
**For highly resistant strains, determine if ****supplemental testing**** is necessary**

## Verification of Patient Results

**Verification of Patient Results**
**...****to follow in Session #4 (April 12)**

## Thank you!