Department of Epidemiology

Bugs and Drugs Elaine Dowell SM MLS (ASCP), Stacey Hamilton MT SM (ASCP), Samuel Dominguez MD PhD,

Sarah Parker MD, and Ann-Christine Nyquist MD MSPH

New this year in Bugs and Drugs In response to a request from our Pediatric Residents, we have made significant changes to the Bugs and Drugs Handbook for 2017. Residents rotating here at CHCO were surveyed this year and a working group comprised of Residents (Robin Ortenberg and Bradley Anderson), Microbiology, Infectious Disease and Antimicrobial Stewardship was formed to improve utility of the current edition of Bugs and Drugs. The most notable change in the handbook is our colorful antimicrobial tables, which have been coded to indicate which drug/bug combinations are most desirable from a treatment perspective. This change was made to assure that the handbook provides maximum value to clinicians selecting antimicrobials for our patients. Color coding of the tables is used to designate appropriate empiric treatments selections for each bug-drug combination similar to the “Sanford Guide for Antimicrobial Therapy”.

Blue shaded boxes indicate first-line therapy, with susceptibility between 75-100%. This medication has good

penetration, limited side-effects and overall strong susceptibilities.

Green shaded box indicates second-line choice with susceptibility between 75-100%, but not first choice due to overly

broad-spectrum, toxicities, or both. May be appropriate as initial therapy before specific bacteria has been identified.

Yellow shaded box indicates susceptibility between 50-74%. Not initial treatment of choice, but can be used if other

medications are not available, patient has significant allergies, or susceptibility known.

Pink shaded box indicates susceptibility for these medications is less than 50%. Consult ID prior to using these

medications and/or use only if known susceptible.

Colorless box with a dash is a drug-bug combination that is not tested per policy.

Pink box with an R indicates this organism is known to have intrinsic resistance to this antibiotic.

Green box with an S indicates that this organism is known to be susceptible to this antibiotic.

Please also note that comments in the footnotes of the tables have been updated with important interpretive information. Clarifying Carbapenem Resistant Enterobacteriaceae (CRE) Carbapenem resistance among enterobacteriaceae is a focus of concern nationally and in January of 2015, CDC changed their definition of this group of gram negative bacteria to include ALL isolates of enterobacteriaceae (enteric gram negative bacteria) that have either intermediate or resistant MICs to one of the carbapenems (imipenem, meropenem, ertapenem or doripenem). Resistance mechanisms that cause this resistance fall into two categories and although detection of a CRE in the Microbiology lab is dependent upon phenotypic characteristics, molecular techniques are required for definitive classification into one of these two groups.

1. Non-CP CRE – resistance is conferred by production of an extended-spectrum Beta-lactamase (ESBL) and/or

an AmpC Beta-lactamase in conjunction with membrane impermeability or active drug efflux pump.

2. CP-CRE or more simply CPE - resistance is conferred by production of a carbapenemase – also called

carbapenemase producing enterobacteriaceae (CP-CRE or more simply CPE).

VOLUME XXXII NUMBER 6 September 2017

CONTAGIOUS COMMENTS Department of Epidemiology

VOLUME XXXII NUMBER 6 September 2017 Page 2

Non-CP CRE includes mechanisms of resistance that may be intrinsic, acquired or transferred between organisms on a plasmid. These organisms as a group are less frequently associated with outbreaks, potentially less contagious and less concerning from an epidemiological standpoint. Many become resistant due to treatment with carbapenems and they do not generally display resistance in ALL other classes of antimicrobials. The CP-CRE or CPE group of organisms produces a carbapenemase enzyme that confers resistance to the carbapenems with some enzymes also conferring resistance to other Beta-lactams. Metallo-beta-lactamases, such as KPC and NDM are included in this group and are associated with outbreaks of difficult to treat organisms. Travel to endemic areas is a risk factor. The Colorado Department of Public Health and Environment (CDPHE) has begun to collect data and in some cases, isolates, to study the emerging resistance patterns of both groups of organisms. At CHCO, all enteric Gram negative rods that are tested for susceptibilities are screened for carbapenem resistance. Ertapenem, imipenem, and meropenem with MICs in the intermediate or resistant range are submitted to CDPHE for screening and confirmed for the production of carbapenemases by molecular methods as needed. At CHCO, non-CP CRE isolates are detected intermittently; we have not had any CP-CRE yet detected. For a nice review of this topic, please see Goodman et al, “Infection control implications of heterogenous resistance mechanisms in carbapenem resistant Enterobacteriaceae (CRE),” Expert Review of Anti-infective Therapy, 2015. MRSA Update Both inpatient and outpatient MRSA rates have remained relatively stable for the past 5 years. CHCO data is submitted through the CDC’s Emerging Infectious Pathogens Program (EIP) and through CDC’s National Healthcare Safety Network (NHSN). When we isolate MRSA from a patient for the first time, two methods are used to confirm the isolate as MRSA. A full antimicrobial susceptibility panel is performed and reported for all first-time MRSA isolates. Methods available at CHCO for MRSA testing and confirmation include PBP2 antigen testing, cefoxitin screen, Microscan MIC and chromagar.


TABLE 1. Gram Positive Organisms: Staphylococcus (% Susceptible)

Antimicrobial Susceptibilities at Children’s Hospital Colorado – 2016

ORGANISMS

NU

MB

ER

OF

ISO

LA

TE

S T

ES

TE

D

ANTIMICROBIALS

Van

com

yci

n

Cli

ndam

yci

n

Tri

met

ho

pri

m /

Su

lfa

Ox

acil

lin

*

Staph aureus (MSSA) 808 100 82 100 100

Staph aureus (MRSA) 437 100 76 98 R

Staph epidermidis 190 100 45 66 35

Staph hominis 43 100 45 86 40

* Includes agents: Nafcillin/Dicloxacillin/Methicillin. If susceptible, also susceptible to

cefazolin/cephalexin.

Oxacillin resistance (MRSA) predicts resistance to ALL beta-lactams including

penicillin, extended spectrum penicillins and cephalosporins.

Confirmation of MRSA is done by PBP2, Cefoxitin Screen or Microscan Panel

Cefoxitin is tested as a surrogate for oxacillin. Oxacillin susceptible or resistant is

based on the Cefoxitin Screen result.

Clindamycin susceptibility is not determined by Cefoxitin Screen or oxacillin

resistance.

The Inducible Clindamycin Test detects inducible clindamycin resistance, due to the

erm genes. The isolate is presumed resistant to clindamycin when the Inducible

Clindamycin Test is positive.

Testing by Microscan Microtiter Panel.


TABLE 2A. Gram Positive Organisms - Streptococcus and Enterococcus (% Susceptible)


ORGANISMS

NU

MB

ER

OF

ISO

LA

TE

S

ANTIMICROBIALS

Pen

icil

lin

Am

pic

illi

n/A

moxic

illi

n

Van

com

yci

n

Cli

ndam

yci

n

Cef

tria

xone

Viridans Strep Group1 – Invasive* 48 50 - 100 96 81

Strep. anginosus Group1 – Invasive (23) 100 - 100 100 100

Beta Strep Group A1 – Invasive (26) 100 S S 96 S

Beta Strep Group B1 (7) 100 S S 75 S

Beta Strep Group B1

(prenatal screens) 498 100 S 100 58 S

Enterococcus faecalis2 143 - 99 100 - -

Enterococcus faecium2 52 - 65 100 - -

Vanc Resistant Enterococcus spp.

(VRE)** (9) R R R - -

1Testing is by Microscan microtiter panel. ( ) = small number 2Testing is by Microscan microtiter panel.

Streptococci:

The Inducible Clindamycin Test (D-test) detects inducible clindamycin resistance due to the erm

gene. For streptococci, resistance to clindamycin is presumed when the D-Test is positive.

* Most non-susceptible viridans group streptococci are intermediate to penicillin, not resistant, and

may be treatable with high dose ampicillin/amoxicillin. Streptococci susceptible to penicillin are

assumed susceptible to ampicillin.

Enterococci:

**Four new VRE patients were identified in 2016. For therapy choices, ID consult recommended

Some species of enterococci are inherently resistant to vancomycin but usually not resistant to

ampicillin, these are E. gallinarum and E. casseliflavis; they are not considered VRE.

Combination therapy should be used in serious Enterococcus spp. Infection (endocarditis and

bacteremia).

Gentamicin Synergy Screen – E. faecalis = 88% susceptible

Gentamicin Synergy Screen – E. faecium = 94% susceptible

Gentamicin Synergy Screens on VRE isolates show 89% are susceptible at CHCO.


TABLE 2B. Gram Positive Organisms: Streptococcus pneumoniae (% Susceptible)

Antimicrobial Susceptibilities at Children’s Hospital Colorado - 2016

Source

Number

IV P

enic

illi

n

IV C

eftr

iax

on

e

Ery

thro

my

cin

Cli

ndam

yci

n

Tri

met

hopri

m/S

ulf

a

Van

com

yci

n

CSF (1)

Insufficient numbers of isolates to report antibiogram.

Patients with pneumococcal meningitis should be started on

vancomycin and ceftriaxone until susceptibilities are

available.

Blood or Sterile

Aspirate 32 81* 93 65 88 71 100

Respiratory 69 59* 94 66 91 74 100

( ) = small numbers

* Refer to organism specific susceptibility. Isolates in the intermediate category

to penicillin may be treated with high dose ampicillin/amoxicillin unless in the CNS.

S. pneumoniae isolates that are susceptible to penicillin are also susceptible to ampicillin

(and amoxicillin if oral choice is appropriate).

Ceftriaxone susceptibility does not imply susceptibility to oral cephalosporins.

Erythromycin susceptibility implies susceptibility to azithromycin.


TABLE 3. Gram Negative Organisms, Non-Urine (% Susceptible)


ORGANISMS

NU

MB

ER

OF

IS

OL

AT

ES

ANTIMICROBIALS

Am

pic

illi

n /

Am

ox

icil

lin

Cef

azoli

n

Cef

tria

xone

Gen

tam

icin

Tri

met

hopri

m /

Su

lfa

Cip

rofl

oxac

in

Mer

open

em

Cef

epim

e

Haemophilus influenzae* Beta-lactamase testing – all

isolates 75

No further testing is routinely performed for beta-

lactamase negative isolates. These isolates are

considered ampicillin susceptible.

Haemophilus influenzae* Beta-lactamase pos and sterile sites

45 19 - 100 - 49 - - -

Escherichia coli 137 51 85 91 92 71 81 99 94

Enterobacter cloacae complex 61 R R IB** 95 90 98 100 95

Klebsiella pneumoniae 63 R 94 98 98 87 98 98 98

Klebsiella oxytoca 50 R 76 96 94 92 100 100 98

Serratia marcescens 33 R R IB** 97 97 100 97 100

Salmonella species 30 83 97 97 - 100 100 100 97

Shigella species (2014-16) (23) 61 - 100 - - 100 100 100

( ) = small numbers

Haemophilus was tested by E-test, all others by Microscan microtiter panel.

*75 Haemophilus influenzae isolates were tested for beta-lactamase production; 47 (62%)

were negative and therefore considered to be ampicillin susceptible. Haemophilus influenzae

isolates that tested positive for beta-lactamase production are still considered susceptible to

ampicillin-sulbactam or amoxicillin-clavulanic acid.

**When IB is indicated above, the organism may have an inducible beta-lactamase. Although

the MIC may indicate susceptibility, beta-lactams should only be used in combination with

a drug from another class to which the organism is susceptible. Cefepime and meropenem

are exceptions and may be used alone.


TABLE 4. Gram Negative Organisms Isolated from Urine (% Susceptible)


ORGANISMS

NU

MB

ER

OF

IS

OL

AT

ES

ANTIMICROBIALS

Am

pic

illi

n /

Am

ox

icil

lin

Am

pic

illi

n/S

ulb

acta

m

Cep

hal

oth

in*

Cef

uro

xim

e

Cef

ota

xim

e/ C

eftr

iaxone

Gen

tam

icin

Nit

rofu

ran

toin

Tri

met

hopri

m /

Su

lfa

Cip

rofl

oxac

in

Cef

tazi

dim

e

Lev

ofl

oxac

in

Cef

epim

e

C. freundii complex (24) R R R R IB** 92 83 67 92 83 100 100

E. coli 1556 53 60 75 95 96 94 98 72 92 97 92 97

Enterobacter cloacae

complex 36 R R R R IB** 97 50 89 97 78 97 100

Klebsiella pneumoniae 126 R 79 88 92 96 96 71 90 97 98 98 98

Klebsiella oxytoca 41 R 78 78 95 100 100 98 88 100 100 100 100

Proteus mirabilis 56 82 86 93 100 100 88 R 84 93 100 93 100

Pseudomonas aeruginosa 57 R R R R R 95 R R 95 95 95 95

( ) Small number of isolates

Testing by Microscan microtiter panel

* Cephalothin results are a surrogate to predict susceptibility to the oral cephalosporin agents:

cephalexin, cefuroxime, cefpodoxime, and cefdinir. Notably for lower tract infection, low level

resistance can often be overcome by high-end dosages due to high concentrations of these agents

in the urine.

**When IB is indicated above, the organism may have an inducible beta-lactamase. Although the

MIC may indicate susceptibility, beta-lactams should only be used in combination with a drug

from another class to which the organism is susceptible. Cefepime and meropenem are exceptions

and may be used alone.


TABLE 5. Non-Enterobacteriaceae (% Susceptible)

Antimicrobial Susceptibilities at Children’s Hospital Colorado– 2016

ORGANISMS

NU

MB

ER

OF

ISO

LA

TE

S

ANTIMICROBIALS

Cef

tazi

dim

e

Azt

reo

nam

Lev

ofl

ox

acin

To

bra

my

cin

Mer

open

em

Min

ocy

clin

e

Tri

met

hopri

m /

Su

lfa

Cip

rofl

oxac

in

Gen

tam

icin

Cef

epim

e

Pseudomonas

aeruginosa

Non CF1 163 93 81 84 95 94 - - 85 82 92

CF-mucoid2 (22) 64 73 - 54 73 - - 54 - -

CF-

nonmucoid2 (27) 78 63 - 55 63 - - 52 - -

Stenotrophomonas

maltophilia2 59 22 - 66 - R 97 95 - - -

1 Non-CF testing performed by Microscan microtiter plate.

2 Cystic fibrosis (CF) Pseudomonas spp. isolates and S. maltophilia isolates tested by E-test.

( ) small number of isolates.


TABLE 6. Candida species (# of Isolates Susceptible)


Antifungal C. albicans

7 tested

C. parapsilosis

13 tested

C. glabrata

2 tested

Interpretation S SDD R S SDD S SDD R

5-Flucytosine 6 - 1 13 - 2 - -

Anidulafungin 7 - - 13 - 2 - -

Fluconazole 7 - - 12 1 - 2 -

Micafungin 7 - - 13 - 1 - 1

Voriconazole 7 - - 13 - - - -

Itraconazole 7 - - 13 - - - -

Testing performed by UCH

Amphotericin and posaconazole - there are no interpretable standards for susceptibility. ID

consultation required to request.

SDD - Susceptible Dose Dependent

The susceptible dose dependent category implies that susceptibility of an isolate is dependent

upon the dosing regimen that is used in the patient. It is necessary to use a dosing regimen

(higher doses, more frequent doses or both) that results in high drug exposure. ID consult

recommended.

*C. krusei is intrinsically resistant to fluconazole (isolates not tested).

Sources from where yeast was isolated:

Blood - 8

Respiratory - 7

Stool – 2

Shunt – 2

Wound - 1

Urine – 1

Aspirate - 1


Table 7. Cumulative Antimicrobial Susceptibility Report for Anaerobic Organisms

Isolates Collected from Selected US hospitals Jan 2010 through December 2012

ANAEROBIC

ORGANISMS

ANTIMICROBIALS

Nu

mb

er o

f Is

ola

tes

Am

pic

illi

n-s

ulb

acta

m (

Un

asyn

)

Nu

mb

er o

f Is

ola

tes

Pip

erac

illi

n/t

azo

bac

tam

(Z

osy

n)

Nu

mb

er o

f Is

ola

tes

Cef

ox

itin

N

um

ber

of

Iso

late

s

Mer

op

enem

Nu

mb

er o

f Is

ola

tes

Pen

icil

lin

/am

pic

illi

n*

Nu

mb

er o

f Is

ola

tes

Cli

nd

amy

cin

Nu

mb

er o

f Is

ola

tes

Met

ron

idaz

ole

Percent Susceptible (%S) and Percent Resistant (%R)

% S

% R

% S

% R

% S

% R

% S

% R

% S

% R

% S

% R

% S

% R

Fusobacterium nucleatum-

necrophorum 27 100 0 27 100 0 27 100 0 27 100 0 44 100 0 27 100 0 27 100 0

Anaerobic gram- positive

cocci 150 88 9 614 99 0 148 94 3 614 98 1 168 100 0 614 79 16 611 96 3

P. acnes 58 100 0 58 100 0 58 100 0 58 100 0 34 100 0 91 9

B. fragilis group 2580 82 6 3959 87 7 3841 65 7 3939 98 1 3839 48 42 3981 98 1

Data adapted from CLSI M100-S26 January 2016.

Isolates collected from selected US hospitals.


CONTAGIOUS COMMENTS Department of Epidemiology©

EDITOR: Carolyn Brock, Senior Administrative Professional

Children’s Hospital Colorado, Dept. of Epidemiology, B-276 13123 E. 16th Avenue, Aurora, CO 80045

Phone: (720) 777-6072; FAX: (720) 777-7295 [email protected]

www.ChildrensColorado.org ** We Recycle! **

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Name: __________________________________________________ E-mail Address: ___________________________________________ Both the Contagious Comments and Bug Watch publications are always posted on Children’s Hospital Colorado website at: https://www.childrenscolorado.org/health-professionals/publications/

Please return your E-mail address to: Carolyn Brock, Children’s Hospital Colorado, Epidemiology – Box B276, 13123 E. 16th Avenue, Aurora, CO 80045 or E-mail address: [email protected].

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Department of Epidemiology

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