Bugs and Drugs Review: Our

Antibiogram and Beyond

Maggie Kline, PharmD
PGY1 Pharmacy Resident
IUH Bloomington Hospital
mkline4@iuhealth.org
Conflicts of Interest
 There are no actual or potential conflicts of interest to disclose.

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Learning Objectives
 Identify appropriate empiric treatment options for community-acquired
pneumonia (CAP), urinary tract infections (UTIs), and skin and soft tissue
infections (SSTIs).
 Identify trends in IU Health Bloomington Hospital’s antibiogram that influence
local treatment recommendations.

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 What is antimicrobial stewardship?
 Efforts to measure and improve use of antimicrobials

 Goals:

Prevent harms
Effectively treat caused by Combat antibiotic
infections unnecessary resistance
antibiotic use

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What is an antibiogram?

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 Blank boxes indicate:
• antibiotic has no intrinsic activity
against the organism
What is an antibiogram? • OR local susceptibility is low

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New antibiogram coming soon!
 Find the most up-to-date antibiogram on the IU Health Team Portal!

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Community-Acquired Pneumonia (CAP)

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Pathogens in CAP Requiring Hospitalization in Adults

N Engl J Med 2015;353:415-27.

• Centers for Disease Control Etiology of Pneumonia in the
Community Study (CDC EPIC)
• 2488 Adults at 5 hospitals in Chicago and Nashville Jan 2010-
June 2012
• Sputum, blood, broncholveolar lavage, endothracheal aspirate,
pleural fluid samples were tested for bacterial and viral
pathogens via culture and PCR collected

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 Pathogens in CAP Requiring Hospitalization in Adults

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N Engl J Med 2015;353:415-27.
 CAP Bugs to Drugs
 The bugs:
 Recommended Inpatient Treatment (IDSA 2019):
 Viruses
 Beta-lactam + macrolide OR respiratory
 Streptococcus pneumoniae fluoroquinolone for 5-7days
 Staphylococcus aureus  Severe patients and patients with risk factors for
 Haemophilus influenzae MRSA or P. aeruginosa, should also have coverage
for those bugs. Recommended to collect blood
 Moraxella catarrhalis and sputum cultures if broad spectrum coverage
 Legionella species is initiated.
 Chlamydophila pneumoniae

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Am J Respir Crit Care Med. 2019;200(7):e45-e67.
Macrolide Monotherapy not Recommended
 Macrolide antibiotics offer coverage against
Streptococcus spp., some gram negative
organisms, and atypical pathogens

 S. pneumoniae is increasingly resistant to

macrolides—not recommended as
monotherapy and should be combined with a
beta-lactam.

 Doxycycline offers similar atypical coverage

and can be used as an alternative to
macrolides in combination with a beta-lactam.

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Our Antibiogram: Choosing your beta-lactam
 Ceftriaxone is commonly used as empiric CAP
treatment, covering S. pneumoniae, and many
gram negative organisms.
 Ceftriaxone drives ESBL resistance rates and
increases C. difficile risk
 Penicillin offers similar S. pneumoniae
coverage. Ampicillin/sulbactam will have
similar coverage and also cover potential gram
negative CAP organisms, representing a more
narrow-spectrum option than ceftriaxone.

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 CAP due to S. aureus
 Clin Infect Dis. 2016;63(3):300-309. Anti-MRSA
Etiology
 Substudy of CDC EPIC looking at S. aureus CAP Patients , n Antibiotics, n
Group
and risk factors (row%)
All CAP 2259 674 (29.8)
⎻ Of 2259 diagnosed with CAP only 37 (1.6%) had
S. aureus isolated (0.7% MRSA, 1% MSSA)
S. aureus 37 34 (91.9)

MRSA 15 14 (93.3)
⎻ Approx. 30% of all patients overall were treated
with anti-MRSA antibiotics
MSSA 22 20 (90.9)

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 Risk Factors for MRSA Pneumonia

Other Potential Risk

Risk Factors
Factors
Recent influenza infection
Prior isolation of MRSA

Chronic hemodialysis
Hospitalization and recent
parenteral antibiotics Active IV drug use

Am J Respir Crit Care Med. 2019;200(7):e45-e67.

Eur J Clin Microbiol Infect Dis. 2018;37(1):51-56.
Ann Am Thorac Soc. 2015; 12 (2): 153-160.
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Am J Respir Crit Care Med. 2013; 188 (8): 985-995.
Respirology. 2016;21(1):157-163.
 Stewardship Tools – MRSA Nasal PCR Swabs

 Nasal PCR swabs detect respiratory colonization by S. aureus.

 Multiple studies show high negative predictive value (NPV) for

isolation of MRSA in respiratory cultures with a negative MRSA nasal
PCR.

 Dangerfield et al. showed a NPV of 99.2% and a positive predictive
value of 35.5%.
Image from:
https://www.infectiousdiseaseadvisor.com/hom
e/topics/prevention/screening-from-nasal-
samples-with-mrsa-has-shown-high-negative-
predicative-values/

 A 2018 meta-analysis of 22 trials with 5163 patients showed a

pooled NPV of 96.5% for all pneumonia types & 98.1% NPV in CAP.

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Clin Infect Dis. 2018;67(1):1-7.
Ann Pharmacother. 2019;53(6):627-638.
 Anaerobic Coverage in Pneumonia
 IDSA: “We suggest not routinely adding anaerobic overage for suspected aspiration pneumonia unless lung
abscess or empyema is suspected.”
 Patients with aspiration pneumonitis will generally experience symptom resolution in 24-48 hours without
antibiotics.
 Oral anaerobes commonly isolated include Fusobacterium, Prevotella, and Peptostreptococcus; many
isolates are susceptible to beta-lactams including amoxicillin.

Infect Dis Clin North Am. 2013;27(1):149-155.

Chest. 1999;115(1):178-183.
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Intern Emerg Med. 2014;9(2):143-150.
Am J Respir Crit Care Med. 2003;167(12):1650-1654.
 Anaerobic Coverage in Pneumonia
Suspected aspiration
pneumonia

Yes Imaging shows evidence of

lung abscess, empyema, or
No
necrosis

Macroaspiration with severe

periodontal disease
Treat for CAP or HAP plus Yes OR
anaerobic coverage >7 days of illness
OR
putrid sputum

No
Infect Dis Clin North Am. 2013;27(1):149-155.
Treat for CAP or HAP without
anaerobic coverage 18
Image from: J Hosp Med. 2020;15(12):754-756.
Am J Respir Crit Care Med. 2019;200(7):e45-e67.
 CAP is often viral – Procalcitonin as a Stewardship Tool
 Procalcitonin (PCT) is a biomarker
released by human epithelial cells in
response to bacterial infection and
downregulated in viral infection.

 Assist with de-escalating antibiotics and

differentiating between bacterial
infection and other causes of respiratory
distress (viral, CHF, edema, atrial
fibrillation, etc.)

 A meta-analysis of 26 trials with 6708

patients in primary care, ED, and ICUs
found a reduction an average 2.4 day
reduction in antibiotic exposure overall.
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Image from Lancet Infect Dis. 2018;18(1):95-107.

 Procalcitonin algorithms are not associated with worse outcomes

Image from Cochrane Database Syst Rev. 2017;10(10):CD007498.

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Lancet Infect Dis. 2018;18(1):95-107.
 Bloomington Hospital’s
Procalcitonin Protocol
 Available in our antibiogram on the team
portal!

 Notes:
 Use in combination with clinical picture.
 PCT can be elevated falsely by prolonged
cardiogenic shock or renal dysfunction
(renally excreted).
 Fungal and malarial infections can
increase PCT.
 Severe stress such as surgery, trauma,
and some cancers can also affect PCT.

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Abi-Mansour T. 2020 Bloomington Hospital Antibiogram.
 COVID-19: What is the likelihood of secondary bacterial infection?

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Clin Microbiol Infect. 2020;26(12):1622-1629.
Study Study Characteristics Subjects, n Estimated prevalence Empiric Notes
bacterial pneumonia co- antibiotic
infection, n (%) use, n (%)
Karaba et al. Open Retrospective; 5 1016 1 proven by culture 677 (69) Probable=clinical
Forum Infect Dis. hospitals within Johns 11 (1.1) probable criteria+improvement with
2020;8(1):ofaa578. Hopkins Health 483 (37) possible antibiotics; Possible=only 1
System clinical criterion

Vaughn et al. Clin Retrospective; 1705 59 (3.5) confirmed by 832 (56.6) -54% had empiric
Infect Dis. community onset co- culture or diagnostic test; (varied 27- antibiotics discontinued
2020;ciaa1239. infections, adults in 38 84% across within 1 day of positive
hospitals in Michigan sites) COVID-19 test
-Excluded azithromycin
monotherapy as empiric
therapy
Garcia-Vidal et al. Retrospective; 989 21 (2) community-acquired - -Having other infections
Clin Microbiol Infect. admitted at least 48 -- 2 MRSA / 4 MSSA (respiratory or not) was
2021;27(1):83-88. hours at Hospital 4 hospital-acquired associated with worse
Clinic of Barcelona 11 ventilator-associated outcomes.
Pickens et al. Retrospective study at 176 28/133 (21.1) who had - -Most common bacteria for
Preprint. medRxiv. Northwestern early BAL, documented early BAL: Strep. spp.,
2021;2021.01.12.2 Memorial Hospital in bacterial superinfection MSSA; only 3 isolates were
0248588. Chicago for intubated resistant to standard CAP
patients. therapy (2 MRSA)
-72 patients (44.4) had - 23
BAL-diagnosed VAP
 Is COVID-19 associated with S. aureus infection?
Infect Control Hosp Epidemiol. 2020;1-2.
 Retrospective cohort study for adults admitted with COVID-19 at all campus for Montefiore Medical Center in the
Bronx, New York
 Prevalence of MRSA was 0.6%, 2.4%, 4.4%, and 5.7% for cultures obtained on hospital days 3, 7,
14, and 28, respectively.

369 MRSA Nasal 12 positive

904 (21.4%) 110 negative
PCRs collected; Of PCRs  2
4221 adult received empiric PCRs  110
these patients, positive
patients with vancomycin negative
122 had cultures (out
COVID-19 within 48 hours cultures
respiratory of 122
of admission (100% NPV)
cultures. patients)

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 COVID-19 and Stewardship

Increased use of antimicrobials with COVID-19 is expected to increase resistance.

Empiric bacterial coverage is recommended for patients with CAP without confirmed COVID-19.
Not all patients with confirmed COVID-19 require empiric antibiotics.

Co-infecting pathogens are likely similar with COVID-19 compared to CAP without COVID-19.

Use stewardship tools to guide de-escalation of antibiotics.

Blood and respiratory cultures

Procalcitonin MRSA Nasal PCRs
if MRSA or MDR suspected
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Ann Intern Med. 2020;173(4):304-305.

Patient Case #1:
 BD is a 64 YOM presents from an assisted living facility with worsening productive
cough, fever (101.2 deg F), and chills. His chest X-ray shows bilateral airspace disease
and he is admitted to the medical-surgery floor for treatment of CAP on 2 L O2 nasal
cannula. COVID-19 swab pending. Based on our local antibiogram, what empiric
treatment is recommended at IUH Bloomington?
 A. azithromycin 500 mg PO once followed by 250 mg PO Q24H for 4 days.
 B. ampicillin/sulbactam 3 gm IV Q8H over 4 hours + azithromycin 500 mg PO Q24H
 C. ceftriaxone 1 gm IV Q24H + doxycycline 100 mg IV Q12H
 D. vancomycin IV pharmacy to dose (MRSA nasal swab)+ ceftriaxone 1 gm IV Q24H
+ doxycycline 100 mg PO Q12H

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Patient Case #1:
 BD is a 64 YOM presents from an assisted living facility with worsening productive
cough, fever (101.2 deg F), and chills. His chest X-ray shows bilateral airspace disease
and he is admitted to the medical-surgery floor for treatment of CAP on 2 L O2 nasal
cannula. COVID-19 swab pending. Based on our local antibiogram, what empiric
treatment is recommended at IUH Bloomington?
 A. azithromycin 500 mg PO once followed by 250 mg PO Q24H for 4 days.
 B. ampicillin/sulbactam 3 gm IV Q8H over 4 hours + azithromycin 500 mg PO Q24H
 C. ceftriaxone 1 gm IV Q24H + doxycycline 100 mg IV Q12H
 D. vancomycin IV pharmacy to dose (MRSA nasal swab)+ ceftriaxone 1 gm IV Q24H
+ doxycycline 100 mg PO Q12H

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CAP Summary
 A large proportion of CAP cases are viral. Staphylococcus aureus pneumonia including MRSA
pneumonia is rare (<2%).

 A recommended regimen for non-severe CAP treatment at IUH Bloomington Hospital is

ampicillin/sulbactam 3-4.5 gm IV Q8H over 4 hours for 5 days in combination with
azithromycin 500 mg IV/PO daily for 3 days.

 Stewardship tools such as procalcitonin algorithms and MRSA nasal swabs can allow more
rapid de-escalation of antimicrobials.

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Urinary Tract Infections (UTIs)

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Types of UTIs Asymptomatic bacteriuria

Uncomplicated Cystitis

Complicated Urinary Tract Infection

•Recurrent cystitis
•Pyelonephritis
•Renal transplant patients
•Cather-associated

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 UTI Treatment Principles
 Differentiate infection from asymptomatic bacteriruria and only treat the latter in select patients.
 Whenever possible, remove or replace urinary catheters.
 Ideal treatments for UTIs concentrate well in the urine.
 Complicated infections (prostatitis, pyelonephritis, urosepsis, bacteremias) cannot be treated with
fosfomycin and nitrofurantoin.

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Clin Infect Dis. 2019 May 2;68(10):1611-1615.
 UTIs – The Bugs
 Per IDSA 2010 Guidelines the most common organisms causing uncomplicated cystitis and pyelonephritis
are gram negative enteric organisms:
 E. coli (75-95%)
 P. mirabilis
 K. pneumoniae

E. coli
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Clin Infect Dis. 2011;52(5):e103-e120.
 Empiric Treatment Guidelines (Females)– IDSA 2010
 Uncomplicated cystitis (oral)  Pyelonephritis
 Nitrofurantoin 100 mg BID 5 days  “Women with pyelonephritis requiring
 Trimethoprim/sulfamethoxazole 160mg/800mg hospitalization should be initially treated with an
BID 3 days intravenous antimicrobial regimen…based on local
resistance data, and the regimen should be
 Fosfomycin 3 gm ONCE* tailored on the basis of susceptibility results (B-
 Alternatively: fluoroquinolones, beta-lactams such III)”
as cephalexin for 3-7 days

 *Locally recommended to reserve fosfomycin for multi-

drug resistant (MDR) organisms due to cost and low
barrier for resistance.

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Clin Infect Dis. 2011;52(5):e103-e120.
 Our local UTI pathogens
Organism Incidence (%)  IUH Bloomington Hospital community-acquired urine
isolates from 2020 (Left)
E. coli 718 (61%)
 209 Staphylococci isolates excluded
Klebsiella spp. other than 164 (14%)
aerogenes
 UTIs due to GPCs may be becoming more prevalent
Enterococcus spp. 117 [92/20] (10%) worldwide, with published studies showing 0.5-
[faecalis/faecium] 26.7% of total isolates as GPCs, primarily E. faecalis.
P. mirabilis 77 (7%)

P. aeruginosa 45 (4%)  If empiric treatment for UTIs only covers gram

negative pathogens, >10% of isolates will not be
Enterobacter cloacae 26 (2%) treated empirically!

Klebsiella (Enterobacter) 24 (2%)

aerogenes
Total 1171
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Sci Rep. 2020;10(1):17658.
Bloomington Gram Negative Susceptibilities
 Recommended empiric oral agents for uncomplicated cystitis (IDSA 2010)

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Bloomington Gram Negative Susceptibilities
 Recommended IV empiric therapy?

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 Bloomington Enterococcus Susceptibilities
 The majority of Enterococcus isolates at
Bloomington are susceptible to ampicillin, the
drug of choice.

 Approx. 8% of isolates are vancomycin-

intermediate or resistant (VRE), the majority of
these are E. faecium

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Recommended Empiric IV Therapy
 Based on empiric susceptibilities for common gram negative Enterobacteriaciae and Enterococcus, our
antibiogram recommends an empiric regimen of:

Gentamicin Approx. 92%

3-5 mg/kg IV Ampicillin 3 of isolated
extended gm Q8H over pathogens
interval 4 hours empirically
dosing* covered

*Extended interval dosing In contrast, ceftriaxone

reduces nephrotoxicity compared monotherapy empirically
to traditional dosing covers only 78% of isolates!
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 Asymptomatic Bacteriuria is common.
Population Prevalence (%)
Healthy women, premenopausal 1-5
Healthy women, postmenopausal 2.8-8.6
Heathy pregnant women 1.9-9.5
Women/men with diabetes 10.8-16/0.7-11
Elderly women/men in LTCF 25-50/15-50
Indwelling catheter use
Short term 3%-5%/day
Long term 100
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Clin Infect Dis. 2019 May 2;68(10):1611-1615.
 Asymptomatic Bacteriuria – To treat or not to treat?
 Do not screen and treat  Screen and Treat
 Pediatric Patients  Pregnant women
 Healthy non-pregnant women  Prior to endoscopic urologic procedures expected
 Older persons in the community or ECFs to damage mucosa

 Renal transplant surgery > 1 month prior

 Non-renal solid organ transplant  No recommendation:
 Patients with spinal cord injury  High risk of neutropenia
 Indwelling urethral catheter
 Elective non-urologic procedures
 Undergoing or living with implantation of urologic
devices

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Clin Infect Dis. 2019 May 2;68(10):1611-1615.
Patient Case #2

 JP is a 58 YOM who presents with flank pain, fever, WBC 10, and urinary urgency. SCr 1.3 (baseline 0.7). VS
are WNL. JP is admitted for treatment of pyelonephritis. He has no history of urinary tract infection. What
empiric antibiotic regimen would you recommend based in IUH Bloomington’s antibiogram?
 A. ceftriaxone 1 gm IV daily
 B. fosfomycin 3 gm PO once
 C. ampicillin 3 gm IV Q8H over 4 hours + gentamicin 3 mg/kg IV extended-interval dosing
 D. cefazolin 1 gm IV Q6H

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Patient Case #2

 JP is a 58 YOM who presents with flank pain, fever, WBC 10, and urinary urgency. SCr 1.3 (baseline 0.7). VS
are WNL. JP is admitted for treatment of pyelonephritis. He has no history of urinary tract infection. What
empiric antibiotic regimen would you recommend based in IUH Bloomington’s antibiogram?
 A. ceftriaxone 1 gm IV daily
 B. fosfomycin 3 gm PO once
 C. ampicillin 3 gm IV Q8H over 4 hours + gentamicin 3 mg/kg IV extended-interval dosing
 D. cefazolin 1 gm IV Q6H

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UTI Summary

Differentiate bacteriuria from true infection and only treat bacteriuria in

pregnant patients and those with upcoming urologic procedures.

Empiric UTI treatment should provide coverage for Enterobacteriaciae

and Enterococcus spp.

IUH Bloomington’s antibiogram suggests combination ampicillin/sulbactam

IV and gentamicin IV provides best empiric UTI coverage.

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Skin and Soft Tissue Infections (SSTIs)

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 SSTIs—The Bugs
 For community-acquired SSTIs, the predominant organisms are S. aureus, and beta-hemolytic
Streptococcus spp. (Group A Strep.)

Staph. aureus Strep. pyogenes

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Images from: https://www.ncbi.nlm.nih.gov/books/NBK470553/
https://www.cdc.gov/groupastrep/diseases-hcp/cellulitis.html
 Treating Purulent Infections Empirically-IDSA
 Adding antibiotic coverage to mild purulent abscesses does not
increase cure rate after incision and drainage (I&D)

 If SIRS criteria are present, then antibiotics directed against S.

aureus should be administered.

 Consider MRSA coverage:

 IV drug use
 Penetrating trauma
 History of MRSA or colonization
 Local susceptibility of S. aureus

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Clin Infect Dis. 2014;59(2):e10-e52.
Bloomington Antibiogram – S. aureus
 Oral options for non-severe SSTIs include cephalexin, doxycycline, SMZ/TMP, and clindamycin

57% of S. aureus
isolates are
MRSA

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 Empiric Treatment Options for
Nonpurulent SSTIs – IDSA
 Target mild cellulitis against Streptococci.
 Cutaneous symptoms may worsen after starting
treatment in some patients due to release of
pyrogens with streptococcal destruction.
 MRSA is not a typical cause of cellulitis.
 Surgical debridement is the treatment of choice
for severe infections such as necrotizing fasciitis.
Empiric treatment should be broad spectrum
such as vancomycin + piperacillin/tazobactam or
vancomycin + cefepime + metronidazole and
include clindamycin for binding of streptococcal
toxins.

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Clin Infect Dis. 2014;59(2):e10-e52.
 S. pyogenes Coverage
 S. pyogenes is susceptible to most beta-lactams including penicillins.
 Clindamycin – generally susceptible
 Doxycycline – variable coverage
 SMZ/TMP – variable coverage
 In vitro studies on low thymidine media show 99% & 100% susceptibility of S. pyogenes isolates though
this has not been confirmed with clinical trials.

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J Clin Microbiol. 2012;50(12):4067-4072.
The Sandford Guide To Antimicrobial Therapy 2020.
 When do wounds need P. aeruginosa coverage?

Personal history
Water exposure Warm climate
in wound culture

Severe infections
High local Patients with
(e.g. necrotizing
prevalence neutropenic fever
fasciitis)

Clin Infect Dis. 2014;59(2):e10-e52. 50

Clin Infect Dis. 2012;54(12):e132-e173.
Anti-Pseudomonas Drugs
 Piperacillin/tazobactam and cefepime have similar rates of P. aeruginosa coverage
 Isolates tend to be more resistant to ciprofloxacin, which has a higher risk for collateral damage as well.

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 Anaerobic Coverage – Local Antibiogram

 Recommended for 2016 Bacteroides spp. Isolates (n=39)

 chronic, previously treated, or severe wound; Percent
Necrotic wounds that have not yet been debrided
Susceptible
 SSTIs related to the axilla, GI tract, perineum, or
female genital tract Metronidazole 97
 Bacteroides spp. susceptibility to clindamycin is 51% Clindamycin 51
locally.
 When anaerobic coverage is needed, using a beta- Amoxicillin/clavulanate 97
lactam/beta-lactamase inhibitor combination or Ampicillin/sulbactam 90
metronidazole are recommended.
 Cefoxitin has potential to be an induce AmpC beta- Piperacillin/tazobactam 100
lactamase production and increase resistance. Meropenem 92
Cefoxitin 85 52
Clin Infect Dis. 2014;59(2):e10-e52.
Clin Infect Dis. 2012;54(12):e132-e173.
Patient Case #3
 SD is a 59 YOF who presents with increased area of swelling, redness, and pain in left lower leg. WBC 12. VS
WNL. Weight 134 kg. Venous Doppler negative for DVT. She is diagnosed with cellulitis and admitted
secondary to another medical issue. What empiric treatment is recommended?
 A. vancomycin IV pharmacy to dose + ceftriaxone 2 gm Q24H
 B. vancomycin IV pharmacy to dose + cefazolin 2 gm Q6H
 C. doxycycline 100 mg PO Q12H
 D. cefazolin 2 gm IV Q6H

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Patient Case #3
 SD is a 59 YOF who presents with increased area of swelling, redness, and pain in left lower leg. WBC 12. VS
WNL. Weight 134 kg. Venous Doppler negative for DVT. She is diagnosed with cellulitis and admitted
secondary to another medical issue. What empiric treatment is recommended?
 A. vancomycin IV pharmacy to dose + ceftriaxone 2 gm Q24H
 B. vancomycin IV pharmacy to dose + cefazolin 2 gm Q6H
 C. doxycycline 100 mg PO Q12H
 D. cefazolin 2 gm IV Q6H

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SSTI Summary

Most SSTIs are caused by S. aureus and S. pyogenes.

Empiric MRSA coverage is recommended in purulent

and severe nonpurulent infections only.

Clindamycin is not recommended as empiric S. aureus or

anaerobic coverage based on local susceptibilities.

55
Conclusion
 Infectious disease guidelines form useful frameworks for empiric therapy that our
local antibiogram can build upon.
 Avoid treatment of colonization or viral infection with antibiotics as able.
Optimizing antimicrobial use is key to limiting resistance development and
improving patient outcomes.
 Our local antibiogram also contains many other helpful references such as
procalcitonin algorithms, antimicrobial dosing, and empiric therapy
recommendations.

56
Bugs and Drugs Review: Our
Antibiogram and Beyond
Maggie Kline, PharmD
PGY1 Pharmacy Resident
mkline4@iuhealth.org