1. Role of MRSA Swabs for De-escalation of Antibiotics in HCAP
Colleen Linsenmayer, Pharm.D.
PGY2 Internal Medicine Pharmacy Resident
Richard L. Roudebush VA Medical Center
This speaker has no actual or potential conflicts of interest to
disclose in relation to this presentation

2. Methicillin-resistant Staphylococcus aureus (MRSA)
Increasingly important pathogen in pulmonary infections
Incidence of MRSA healthcare-associated pneumonia (HCAP) is predicted to be %.
Associated with significant morbidity and mortality
IDSA Guidelines, citation 1
Incidence depends on patient risk factors and local epidemiological patterns
MRSA pneumonia is associated with significant morbidity and mortality particularly if antibiotic therapy targeting MRSA is not included in an initial empirical regimen.
Niederman MS et al. Am J Respir Crit Care Med. 2005;171:
Dangerfield B et al. Antimicrobial Agents Chemother. 2014;58(2):

3. IDSA HAP Guidelines Late onset (≥5 Days) or risk factors for
HAP, VAP or HCAP suspected
Late onset (≥5 Days) or risk factors for
multi-drug resistant (MDR) pathogens
Broad spectrum antibiotic therapy for
MDR pathogens (Including MRSA)
Risk factors:
Niederman MS et al. Am J Respir Crit Care Med. 2005;171:

4. IDSA HAP Guidelines How do you de-escalate in absence of adequate
Consider de-escalation of antibiotic based on:
Results of lower respiratory tract cultures are available
Patient’s clinical response
How do you de-escalate in absence of adequate
lower-respiratory cultures?
And to combat overuse of antibiotics the IDSA guidelines so recommend de-escalation based on microbiological cultures and clinical response of the patient
However what they did not address how to de-escalate antibiotics in the absence of adequate cultures which is commonly the case in many of our patients. Many physicians are reluctant to discontinue or de-escalate empiric antibiotics when cultures are unavailable.
One way to determine safety and appropriateness of de-escalation is to evaluate the patient for the presence or absence of colonization
Niederman MS et al. Am J Respir Crit Care Med. 2005;171:

5. Pathogenesis Entry of MRSA Colonization Aspiration Infection
HAP requires the entry of microbial pathogens into the lower respiratory tract, followed by colonization, which can then over-whelm the host’s mechanical (ciliated epithelium and mucus), humoral (antibody and complement), and cellular (polymorpho-nuclear leukocytes, macrophages, and lymphocytes and their respective cytokines) defenses to establish infection. Aspiration of oropharyngeal pathogens or leakage of bacteria around the endotracheal tube cuff is the primary route of bacterial entry into the trachea
Patients are most likely to develop HCAP due to a MDR pathogen following aspiration of the organism from the patient’s oropharynx
Niederman MS et al. Am J Respir Crit Care Med. 2005;171:

6. MRSA Colonization
Identifying patients with MRSA colonization may guide initial antibiotic treatment and isolation measures
MRSA swabbing is a standard method for screening in many facilities for MRSA screening
Patients colonized with MRSA are at a higher rate of infection and act as a resevoir for potential transmission to other patients
Nasal MRSA screening has been shown to be the most sensitive at detecting patients who are MRSA carriers
Dangerfield B et al. Antimicrobial Agents Chemother. 2014;58(2):

7. MRSA Nasal Colonization
MRSA nasal colonization can be reliably detected using nasal swab PCR test
Presence of MRSA nasal colonization has been correlated with the development of subsequent MRSA infections
Most patients with HCAP due to MDR organisms develop infection following aspiration of the organism for patient’s oropharynx followed by tracheal colonization
MRSA nasal swabs can have a powerful impact on the course of therapy depending on whether positive or negative
Dangerfield B et al. Antimicrobial Agents Chemother. 2014;58(2):
Boyce JM et al. Antimicrobial Agents Chemother. 2013;57(3):

8. Predictive Value of MRSA Nasal Swabs for MRSA Pneumonia
Test Characteristic
Result
95% Confidence Interval
Sensitivity (%)
88.0
67.6 – 96.9
Specificity (%)
90.1
86.6 – 92.8
Positive predictive value (%)
35.4
24.0 – 48.7
Negative predictive value (%)
99.2
97.4 – 99.8
Authors found that the nasal MRSA PCR test has a mediocre positive predictive value but an excellent negative predictive value for MRSA pneumonia
PCR testing was usually ordered for clincal diagnostic purposes (in both ICU and IM patients)
Included CAP, HCAP, and HAP. HCAP (the largest pt group with n = 238) actually found a 100% NPV
Clinical implication of these results is that patients treated empirically with antibiotics to treat MRSA may be reasonably used to guide de-escalation
Dangerfield B et al. Antimicrobial Agents Chemother. 2014;58(2):859-62

9. MRSA Nasal Swabs - Negative Predictive Value (NPV)
Clinical Trial
Population
Culture Site
NPV
Harris et al.
Non-ICU
Any Body Site
98%
Robicsek et al.
All admissions/
ICU transfers
Robissek et al (Subgroup)
Respiratory
Sarikonda et al
ICU
84.4%
Additional studies looking at negative predictive value of MRSA swabs
Difference in NPV in this trial may be attributed to all ICU pts vs mixed and higher prevalence of colonization and infection
Harris AD et al. Antimicrobial Agents Chemother. 2010;54(8):
Robicsek A, et al. J Clin Microbiol ;46(2):
Sarikonda KV, et al. Crit Care Med. 2010;38(10):

10. Clinical Implications
Patients treated empirically with antibiotics to treat MRSA may reasonably used to guide de-escalation
Piperacillin/Tazobactam + Vancomycin
Clinical implication of these results is that patients treated empirically with antibiotics to treat MRSA may be reasonably used to guide de-escalation
Dangerfield B et al. Antimicrobial Agents Chemother. 2014;58(2):
Boyce JM et al. Antimicrobial Agents Chemother. 2013;57(3):

11. Discontinuation of Empiric Vancomycin
Population: patient receiving empiric vancomycin for suspected or proven HCAP with no adequate lower-respiratory cultures
If nasal + throat MRSA cultures were negative then de-escalation of vancomycin was recommended
Results: no difference in mortality compared to previous study of pneumonia patients who underwent de-escalation of antibiotics when respiratory cultures were not obtained
Take home message by the authors was that when there was no difference in mortality when vancomycin was discontinued
The in-hospital mortality in our study (7.7%) was similar to a mortality rate of 10.7% in a previous study of pneumonia
patients who underwent de-escalation of antibiotics when respiratory cultures were not obtained
Boyce JM et al. Antimicrobial Agents Chemother. 2013;57(3):

12. Debunking Myths
“The patient’s nasal swab may be negative because they received empiric vancomycin therapy prior to the admission nasal swab”
Vancomycin has been shown to have little effect on staphylococcus aureus nasal colonization and seldom would eradicate MRSA in the first several days of therapy
Boyce et al
Boyce JM et al. Antimicrobial Agents Chemother. 2013;57(3):

13. Clinical Pearl Patie nt meet s the follo wing criter ia:
Empiric HCAP Treatment
Patie nt meet s the follo wing criter ia:
1) Blood cultur es negati ve x 48 hours
2) Negat ive MRSA nasal swab
Consider discontinuation of
MRSA-directed antibiotic

14. Summary
MRSA pneumonia is unlikely in patients who are not colonized and have no evidence of MRSA bacteremia
Data suggests that MRSA PCR nasal swabs have negative predictive value of up to 99% for MRSA pneumonia
A negative MRSA swab can be reasonably used to guide antibiotic de-escalation for HCAP

15. Role of MRSA Swabs for De-escalation of Antibiotics in HCAP
Colleen Linsenmayer, Pharm.D.
PGY2 Internal Medicine Pharmacy Resident
Richard L. Roudebush VA Medical Center