De-escalation of Anti-MRSA Antibiotics for Pneumonia in ......De-escalation of Anti-MRSA Antibiotics for Pneumonia in Hospitalized Patients with or without SANSS Hanna Burgin, Pharm.D

De-escalation of Anti-MRSA Antibiotics for Pneumonia in Hospitalized Patients

with or without SANSSHanna Burgin, Pharm.D.PGY1 Pharmacy Resident

UC Health – West Chester Hospital

**The speaker has no actual or potential conflicts of interest in relation to this presentation**

Objectives

• Discuss the antimicrobial resistance problem

• Define Staphylococcus aureus nasal surveillance screening (SANSS)

• Describe negative (NPV) and positive predictive values (PPV) of SANSS for pneumonia

• Evaluate data regarding de-escalation of anti-methicillin resistant Staphylococcus aureus (MRSA) antibiotics with and without SANSS

Antimicrobial Resistance

CDC: Antibiotic Resistance threats in the United States, 2013. [Online]. Retrieved on 30 Mar 2018 from,

https://www.cdc.gov/drugresistance/pdf/ar-threats-2013-508.pdf

Hicks L, et al. N Engl J Med 2013; 368: 1461-1462.

Pneumonia

• Annually in the U.S.

• Hospitalizations: 1 million

• Deaths: 50,000

• 8th leading cause of mortality

US HHS. CDC: National Center for Health Statistics: Pneumonia, 2017. [online] Retrieved on 15 Oct 2017 from,

https://www.cdc.gov/nchs/fastats/pneumonia.htm

Signs & Symptoms• Fever • Chills• Dyspnea • Productive cough • Altered mental status• Rust-colored sputum or

hemoptysis • Chest pain • Worsening respiratory status

Physical Examination & Imaging

• Tachypnea• Tachycardia • Dullness to percussion • Chest wall retractions • Grunting respirations • Diminished breath sounds • Inspiratory crackles • Chest x-ray

Laboratory Values & Cultures• Leukocytosis• Shift to the left

• Bandemia• Elevated neutrophils

• Hypoxia• Increased respiratory

requirements• Arterial blood gas

abnormalities

Kalil A, et al. Clin Infect Dis 2016; 63: e61.

Cilloniz C, et al. Int J Mol Sci 2016; 17: 2120.

Pneumonia Classification

OutpatientHospital

Admission

Day 0 – 2

CAP HAP

HCAP

Inpatient

Day 3

Intubation >48 hours

VAP

• Community-acquired pneumonia (CAP)• Healthcare-associated pneumonia (HCAP)• Hospital-acquired pneumonia (HAP)

• Ventilator-associated pneumonia (VAP)


CAP• S. pneumoniae• S. aureus (MSSA)• H. influenzae• M. pneumoniae• C. pneumoniae• Legionella species • Gram negative bacilli

HCAP

HAP/VAP• S. pneumonia• S. aureus (MSSA/MRSA) • H. influenzae• P. aeruginosa• K. pneumonia• Legionella pneumophila• Acinetobacter species


Cilloniz C, et al. Int J Mol Sci 2016; 17: 2120.

Treatment of Pneumonia

CAP Treatment

First line: β-lactam + macrolide

Alternative: • Respiratory fluoroquinolone

HCAP/HAP/VAP Treatment

First line: anti-pseudomonal β-lactamAlternative: • Respiratory fluoroquinolone

± MRSA coverage: • Vancomycin• Linezolid

± Additional anti-pseudomonalcoverage (i.e. aminoglycoside)

Mandell L, et al. Clin Infect Dis 2007; 44: S27-S72.

MRSA

Key

• ABCs: Active bacterial

core surveillance

• CA: community-

acquired

• HO: healthcare-

associated

• HACO: hospital-

acquired

United States Department of Human and Health Services, Centers for Disease Control and Prevention 2013; 1-114.

MRSA Antibiotic Coverage

• Presence of risk factors often requires empiric coverage using anti-MRSA antibiotics

• Common anti-MRSA antibiotics used for pneumonia in hospital setting:

Antibiotic Route of Administration

Vancomycin IV

Ceftaroline IV

Linezolid IV, oral (PO)


MRSA Colonization

Siegel S, et al. Annu Rev Microbiol 2015; 69: 425-444.

Respiratory Culture Methods

Technique Invasiveness NPV

Sputum Non-invasive Poor

BAL Invasive Moderate

Endotracheal aspirate Invasive Moderate

SANSS Non-invasive Strong

BAL, Bronchoaveolar lavage; NPV, negative predictive value

Barret J, et al. Arch Surg 1999; 144: 1243-1247.

Dhingra V, et al. Indian J Allergy Asthma Immunol 2003; 17: 67-69.

Garcia-Vazquez E, et al. Arch Intern Med 2004; 164: 1807-1811.


Nikbakhsh, et al. Iran J Pathol 2015; 10: 35-40.

Scholte J, et al. J Clin Microbiol 2014; 52: 3597-3604

Shin Y, et al. J Korean Med Sci 2011; 26: 865-869

Tetenta S, et al. Respirology 2011; 16: 86-89.

Staphylococcus aureus Nasal Surveillance Screening (SANSS)

NPV and PPV of SANSS

Acuna-Villaorduna C, et al. Am J Infect Control 2017. 45: 1081-1085.

NPV and PPV of SANSS

MRSA Nasal Colonization for Predicting Clinical MRSA Infections

MRSA infection Sensitivity (95% CI)

Specificity (95% CI) Positive predictive value (95% CI)

Negative predictive value (95% CI)

MRSA pneumonia 76.9 (60.7-88.9)

71.4 (69.7-73.0) 3.5 (2.4-5.0) 99.6 (99.3-99.8)

MRSA skin and soft tissue infection

60.0 (49.7-69.5)

71.8 (70.1-73.4) 6.6 (4.9-8.2) 98.1 (97.6-98.7)

MRSA bloodstream infection

80.5 (65.1-91.2)

71.5 (69.8-73.1) 3.9 (2.8-5.4) 99.6 (99.2-99.8)

Any culture-confirmed MRSA infection

74.4 (68.2-80.5)

74.0 (72.3-75.6) 17.0 (14.5-19.6) 97.6 (96.8-98.2)


MRSA Colonization and Lower Respiratory Tract Infections (LRTIs)

Tilahun B, et al. Am J Crit Care 2015; 24: 8-11.



MRSA Nasal Cultures versus MRSA Respiratory Cultures

Respiratory cultures n = 165

Nasal cultures MRSA positive MRSA negative

MRSA positive 8 (5%) 20 (12%)

MRSA negative 2 (1%) 135 (82%)


Sensitivity, Specificity, PPV, and NPV of SANSS

Variable Percentage

Sensitivity 80.0

Specificity 87.1

PPV 28.6

NPV 98.5


Predictive Value of SANSS in Pneumonia

Dangerfield B, et al. Antimicrob Agents Chemother 2013; 58: 859-864.

Sensitivity, Specificity, PPV, and NPV of SANSS

Variable Percentage

Sensitivity 88.0

Specificity 90.1

PPV 35.4

NPV 99.2



SANSS Predictive Value by Pneumonia Type

Pneumonia type (n) Sensitivity, % Specificity, % PPV, % NPV, %

All (435) 88.0 90.1 35.4 99.2

CAP (149) 77.8 90.7 35.0 98.4

HCAP (238) 100.0 88.9 34.2 100.0

HAP (48) 66.7 95.6 50.0 97.7



NPV and PPV for SANSS in Pneumonia

Year Design/Study Population Objective Results

2017Acuna-Villaorduna C, et al.

Retrospective cohort study Non-ICU and ICU patients

Evaluation of positive MRSA nasal culture results

• NPV: 99.6%• PPV: 3.5%

2015Tilahun B, et al.

Retrospective cohort study ICU patients

Relationship between MRSA nasal swab and MRSA LRTI occurrence in the ICU

• NPV: 98.5%• PPV: 28.6%

2013Dangerfield B, et al.

Retrospective cohort study Non-ICU and ICU patients

Prediction of pneumonia via MRSA nasal swab PCR assay

• NPV: 99.2%• PPV: 35.4%




Use of SANSS in Antimicrobial Stewardship

Baby N, et al. Antimicrob Agents Chemother 2017; 61: e02432-16.

SANSS PCR and Antimicrobial De-escalation

SANSS PCR and Antimicrobial De-escalation


MRSA-Targeted Antibiotic Therapy Outcomes

Parameter Pre-PCR (n = 27)

PCR (n = 30)

P value

Duration of therapy

Hours 74 ± 48.9 27.4 ± 18.7 <0.0001

Days 4.0 ± 2.0 2.13 ± 0.86 <0.0001

Total IV vancomycin doses 4.2 ± 3.1 1.7 ± 1.5 0.005

Total IV vancomycin (mg) 5,394.4 ± 3,483.5 2,865 ± 2,579.8 0.003

No. of vancomycin levels (%)

0 14 (51.9) 25 (83.3) --

1 8 (29.6) 5 (16.7) --

2 5 (18.5) 0 (0) --

Per patient average no. of levels 0.67 0.17 --

Willis C, et al. Am J Health-Syst Pharm 2017; 74: 1765-1773.

Pharmacist-Driven SANSS Protocol


Clinical Outcomes

Outcome Pre-protocoln = 150

Post-protocoln = 150

Median vancomycin DOT, days 4.2 2.1

Median hospital LOS, days 8 7

Vancomycin-associated AKI, n (%) 1 (0.7) 0 (0)

In-hospital mortality, n (%) 3 (2.0) 3 (2.0)

DOT, days of therapy; LOS, length of stay; AKI, acute kidney injury




Use of SANSS in Antimicrobial Stewardship

Year Design/Study Population Objective Results

2017Baby N, et al.

Retrospective study ICU patients

Evaluation of pharmacist initiated MRSA PCR testing on duration of MRSA antimicrobial therapy in suspected pneumonia

Duration of anti-MRSA antimicrobial therapy (hours)• Pre-PCR: 74 ± 48.9• PCR: 27.4 ± 18.7

2017Willis C, et al.

Retrospective, single-center, quasi-experimental, pre-post cohort study Non-ICU patients

Evaluation of impact of pharmacist-driven SANSS protocol using MRSA PCR assays

Duration of anti-MRSA antimicrobial therapy (days)• Pre-protocol: 4.2• Post-protocol: 2.1



UC Health SANSS Process

• SANSS process implementation: August 19, 2015

• Non-invasive culture technique to identify MRSA colonization in pneumonia

• Aseptic collection

• Obtained within 24 hours of initiation of anti-MRSA antibiotic therapy

• Must have suspected or confirmed pneumonia

• Recommended in medicine and surgery units

• Use in ICU is under discretion of provider

• Consider de-escalation of anti-MRSA antibiotics, if negative


UC Health: Interprofessional Medication Newsletter. 2015; 1.

Specific Aims

Experimental Design & Methods

• Retrospective, single-center

• Data collection through electronic medical record • Patients with suspected and confirmed pneumonia pre- and post-

implementation of SANSS (August 19, 2015)

Pre-SANSS implemenetation:patients screened for

enrollment from June 30, 2015 backward and enrolled until

power is met

Post-SANSS implemenetation:patients screened for

enrollment from January 1, 2016 onward and enrolled

until power is met

Severity of Disease

Parameters Pre-SANSSn = 64

Post-SANSSn = 64

P-value

Long-term acute care facility resident, n (%) 20 (31%) 15 (23%) 0.357

Co-morbid diseases, n (%)

CHF 13 (20%) 15 (23%) 0.831COPD 15 (23%) 15 (23%) 0.835

CKD 16 (25%) 17 (27%) 1.000Liver disease 0 (0%) 4 (6%) 0.128

DM 17 (27%) 19 (30%) 0.844Neoplastic disease 21 (33%) 20 (31%) 1.000

Cerebrovascular disease 13 (20%) 24 (38%) 0.051Presence of pleural effusion, n (%) 33 (52%) 31 (48%) 0.860Severity of illness, median (IQR) 99.5 (85 – 130.75) 115.5 (97.25 – 136.75) 0.039

CHF, congestive heart failure; COPD, chronic obstructive pulmonary disease; CKD, chronic kidney disease; DM, diabetes mellitus

• Used modified version of Pneumonia Severity Index (PSI) to estimate 30-day mortality data by risk

class which included: demographic factors, coexisting conditions, initial physical examination

findings, and initial laboratory findings

Fine M, et al. N Engl J Med 1997; 336: 243-250.

Primary Outcomes

Primary Outcome Pre-SANSSn = 64

Post-SANSSn = 64

P-value

Hospital length of stay, hours (median, IQR) 120 (54 – 126) 144 (120 – 192) 0.109

Duration of anti-MRSA antibiotic therapy, hours (median, IQR) 45.5 (25.25 – 68.5) 54.5 (35.5 – 69) 0.443

ICU†, hours (median, IQR) 48 (25 – 69) 54 (35 – 69) 0.645

Time from anti-MRSA antibiotic initiation to SANSS result, hours (median, IQR)

-- 50 (41 – 62.5) --

ICU†, hours (median, IQR) -- 44 (40 – 47) --

Time to de-escalation of anti-MRSA antibiotic from SANSS result, hours (median, IQR)

-- 5 (1.75 – 37)* --

ICU†, hours (median, IQR) -- 4 (1 – 7.5)* --

Time from SANSS collection to result, hours (median, IQR) -- 44 (39 – 49) --

ICU†, hours (median, IQR) -- 44 (40 – 47) --

Provider de-escalating anti-MRSA therapy 0.430

Pharmacist 16 (25%) 21 (33%)

--Prescriber 38 (59%) 37 (57%)

Discharge 10 (16%) 6 (10%)

Re-initiation of anti-MRSA antibiotics within 30 day period of discontinuation, n (%)

-- 13 (20%) --

*Only included patients with anti-MRSA antibiotic de-escalated after SANSS resulted†ICU n = 25 per group

IQR, interquartile range; MRSA, methicillin-resistant Staphylococcus aureus

Post-SANSS Respiratory Cultures

Type of Respiratory Culture Respiratory Culture Collected within 48 hours

n = 29

Respiratory Culture Collected within 5 days

n = 39

Sputum, n (%) 21 (72%) 28 (71%)

Endotracheal aspirate, n (%) 0 (0%) 0 (0%)Bronchial wash, n (%) 0 (0%) 1 (3%)

Bronchoalveolar lavage, n (%) 8 (28%) 10 (26%)

Post-SANSS Respiratory Cultures

Respiratory Culture Collected within 48 hours

Respiratory Culture Collected within 48 hoursn = 29

SANSS result MRSA Positive MRSA Negative

MRSA Positive 1 (3%) 6 (21%)MRSA Negative 0 (0%) 22 (76%)

Respiratory Culture Collected within 5 days

Respiratory Culture Collected within 5 daysn = 39

SANSS result MRSA Positive MRSA Negative

MRSA Positive 1 (3%) 11 (28%)

MRSA Negative 0 (0%) 27 (69%)

Post-SANSS Predictive Values

SANSS Predictive Values (Overall)

NPV, % PPV, %

Respiratory Culture Collected within 48 hours 100 14Respiratory Culture Collected within 5 days 100 8

NPV, negative predictive value; PPV, positive predictive value

SANSS Predictive Values (ICU)

NPV, % PPV, %

Respiratory Culture Collected within 48 hours 100 50Respiratory Culture Collected within 5 days 100 33

NPV, negative predictive value; PPV, positive predictive value

Conclusions

• Inappropriate prescribing of antimicrobials has been linked to the emergence of MDROs

• Anti-MRSA antibiotics may be used as empiric therapy in suspected and confirmed pneumonia

• SANSS has strong NPV and poor PPV

• SANSS promotes shorter anti-MRSA antibiotic duration by providing evidence for de-escalation

• PCR-based SANSS may offer an advantage in time to antibiotic de-escalation over culture-based testing

Acknowledgements

• Suzanne Van Fleet, Pharm.D.

• Lindsay Benedik, Pharm.D., BCPS, BCGP

• Riane Ghamrawi, Pharm.D., BCPS

• Gaurav Khanna, M.D.

• Marcie Malone, Pharm.D.

**The speaker has no actual or potential conflicts of interest in relation to this presentation**

Hanna Burgin, Pharm.D.PGY1 Pharmacy Resident

UC Health – West Chester Hospital

De-escalation of Anti-MRSA Antibiotics for Pneumonia in Hospitalized Patients

with or without SANSS

Documents

De-escalation of Anti-MRSA Antibiotics for Pneumonia in ......De-escalation of Anti-MRSA Antibiotics for Pneumonia in Hospitalized Patients with or without SANSS Hanna Burgin, Pharm.D