Jim Hoehns, Pharm.D.

Healthcare –Associated Pneumonia

Patient Case

93 female LTCF patient presents with dyspnea and fever. EMS notified; brought to ER

Medical hx: Afib, dementia, spinal stenosis, R hip OA, LVEF 55%

Vitals: 137/97 P-98, 102F, RR 22, O2 initially 75%, then 93% on 3L

Exam: Decreased breath sounds on the right

Labs: WBC 8.8, Cr = 0.7, Hgb = 14 CXR: congestive changes; right basilar patchy

opacity with positive infiltrate Diagnosed with pneumonia and admitted

Poll

93 y.o. F from LTCF with pneumonia. Treatment?

A. Levofloxacin B. Levofloxacin + vancomycin C. Levofloxacin + Pip/Tazo +

vancomycin D. Ceftriaxone E. Ceftriaxone + azithromycin

PICO

P: Elderly LTCF patients with pneumonia

I: Guideline based antibiotics C: Non-guideline based antibiotics O: Mortality or clinical outcomes

2005 – ATS/IDSA Guidelines

HAP: hospital acquired pneumonia Arises 48hrs or more after admission

HCAP: health-care associated pneumonia** Hospitalized within last 90 days; LTCF, IV therapy,

chemotherapy, wound therapy, or attended a hospital or hemodialysis clinic in last 30 days

VAP: ventilator associated pneumonia Arises more than 48-72 hrs after intubation

HCAP included in spectrum of HAP and VAP HCAP: need therapy for MDR pathogens

Acknowledges most evidence for VAP Timing of pneumonia is important

“Early onset HAP/VAP”: within 4 days of hospitalization (likely sensitive bacteria)

“Late onset HAP/VAP”: at 5 days or later (MDR pathogens more likely)

2005 – ATS/IDSA Guidelines

2005 – ATS/IDSA Guidelines

HCAP etiology? “elderly residents of LTCFs have a

spectrum of pathogens that more closely resemble late-onset HAP and VAP”

Study 1▪ Staph aureus (29%), enteric GNRs (15%),

Strep pneumoniae (9%), Pseudomonas (4%) Study 2 – “failed to respond to 72 hrs of

abx”▪ MRSA (33%), GNRs (24%), Pseudomonas

(14%)

Goal: evaluate effectiveness of guideline-based therapy (GBT) compared with other antimicrobial regimens and to identify subgroups of patients with HCAP who receivedgreatest benefit from GBT.

Methods

Cohort study; 346 U.S. hospitals Inclusion

Patient discharge between Jul 2007 – Jun 2010

Age ≥ 18 yrs with▪ Primary ICD-9 dx of pneumonia, OR▪ Secondary dx of pneumonia, paired with primary

dx of respiratory failure, ARDS, respiratory arrest, sepsis, or influenza

HCAP▪ If dx of ESRD/dialysis in first 2 hospital days, OR if

admit from a SNF, OR if DC from hospital in past 90 days, OR taking immunosuppressant drugs

Methods

Exclusion Transfer patients (could not assess initial

severity or outcomes) Length of stay ≤1 day Cystic fibrosis Attending not expected to treat

pneumonia DRG inconsistent with pneumonia Any pt who did not have a CXR and

begin antimicrobials within 48hrs of admission

Methods

Data elements Age, sex, race, marital and insurance

status, comorbidities, tests, medications and treatments, physician specialty, comorbidities (via a software program)

Hospitals: region, bed size, rural/urban, teaching status

Methods

GBT 1 abx against MRSA and 1 abx against

Pseudomonas Main predictor variable

Non-GBT: all other abx regimens Primary outcome: in-hospital mortality Secondary outcomes

7 day mortality, initiation of mechanical ventilation or admission to ICU, readmission in 30 days, cost, length of stay, clostridium difficile infection (CDI)

Statistics

Categorical variables Frequencies and proportions

Continuous variables Medians with IQRs

Logistic regression model for treatment Propensity scores for GBT vs. non-GBT

Adjusted analyses Sensitivity analysis

Explore effect of hypothetical unmeasured confounders

Results

N=85,097 patients from 346 hospitals 31,949 (37.5%) received GBT Of those not receiving GBT, 82%

received standard therapy for CAP GBT patients

Younger More likely male More chronic disease More severe pneumonia

Sensitivity Analysis: “A single potential confounder wouldhave to be present in 30% of the GBT patients (and none of the non-GBT patients) and have an OR of 3.0 in order to find a statistically significant benefit to GBT”

Discussion

Explanations Selection bias: physicians refer GBT for

sickest patients GBT might harm some patients▪ ADE’s, resistance, CDI, complications of IV or

prolonged hospitalization

Limitations

Observational nature Worked solely with claims; could

miss important confounders No microbiologic data Modified the ATS/IDSA guidelines

Used 1 vs. 2 drugs for pseudomonas (results were same regardless)

Author’s Discussion

To date, no RCTs of GBT for HCAP Findings question the necessity of

treating all HCAP patients with GBT Better models needed to identify at-

risk patients for MDR pathogens 2010: Only 40% of patients with

HCAP receive GBT

Discussion - Others

Ewig S et al. Curr Opin Infect Dis 2012;25:166-175. HCAP poorly predictive of MDR pathogens Frequency of MDR pathogens far lower

than supposed in the original guideline document

HCAP concept results in tremendous overtreatment without any evidence for improved outcomes

Summary

IDSA is currently revising HAP, VAP, and HCAP guidelines

1 MRSA antibiotic and 2 Pseudomonas antibiotics seem to be “too much” given the available evidence for routine treatment of a LTCF patient hospitalized with pneumonia

Poll

93 y.o. F from LTCF with pneumonia. Treatment?

A. Levofloxacin B. Levofloxacin + vancomycin C. Levofloxacin + Pip/Tazo +

vancomycin D. Ceftriaxone E. Ceftriaxone + azithromycin