2015 Year in Infectious Diseases
J. Alex Viehman, MD, Clinical Assistant Professor of Medicine
Division of Infectious Disease, University of Pittsburgh Medical Center
Overview
New gram negative antibiotics approved
HIV treatment initiation data
Community acquired pneumonia
Vertebral osteomyelitis treatment
Intra-abdominal infections
New Antibiotic Approvals 2014-2015
Two gram negative acting agents have been approved by
the FDA
Ceftolozane/Tazobactam (Indications: UTI/Pyelo, IAI)
Ceftazidime/Avibactam (Indications: UTI/Pyelo, IAI)
Both are beta-lactam/beta-lactamase combinations
Each agent has one previously approved component
(Tazobactam, Ceftazidime) and one new component:
Avibactam: Non-beta-lactam, beta-lactamase inhibitor
Ceftolozane: Novel antipseudomonal cephalosporin
Intra-abdominal Infections: Ceftaz/Avi
Phase II Trial: Comparative study of the efficacy and
safety of ceftazidime/avibactam plus metronidazole versus
meropenem in the treatment of complicated intra-
abdominal infections in hospitalized adults
Intra-abdominal infection + operation for source control
Arm 1: Ceftazidime/Avibactam + Metronidazole 5-14 days
Arm 2: Meropenem + placebo 5-14 days
Outcome:
Resolution or significant reduction of infection 2 week after
last dose, with no further antibiotics or surgeries
Lucasti C et al. JAC 2013: 68 183-1192
Results
Clinical response at test of cure
Ceftaz/Avi 91.2% (62/68)
Meropenem 93.4% (71/76)
Study not powered to show non-inferiority
Only two Meropenem Resistant isolates
Lucasti, C et al JAC 2013: 68 183-1192
Ceftazidime/Avibactam: Take home
Good efficacy in this trial
Except:
Mostly carbapenem-sensitive E. coli
Relatively healthy patients
Need additional data for Carbapenem -Resistant
organisms from clinical patients
Intra-abdominal Infections:
Ceftolozane/Tazobactam
Patients: IAI + drainage procedure
Intervention: Ceftolozane/tazobactam + metronidazole
Control: Meropenem + placebo
Duration 4-14 days
Outcome: Clinical cure at 24-32 days after therapy end
Solomkin J et al. CID 2015;60(10): 1462-71
Results: Solomkin et al
Subgroup:
Pseudomonas Clinical Cure:
Ceftolozane/Tazo: 100%
Meropenem: 93.1%
Ceftolozane/Tazobactam: Take Home
Non-inferior to meropenem
Suggestion of better clinical efficacy in key pathogens
Pseudomonas
ESBL
How to use:
1. Reasonable indication for ID consultation
2. Reserve Ceftazidime/Avibactam for CRE due to KPC
Does not work against metalo-beta-lactamases
Does not work against Acinetobacter or carbapenem-resistant
Pseudomonas
Do not presume sensitivity (try to get lab confirmation)
3. Reserve Ceftolozane/Tazobactam for MDR
Pseudomonas
Do not presume sensitivity (try to get lab confirmation)
For ESBL that remains susceptible to carbapenem:
Carbapenem remains first line beta-lactam
HIV Treatment: START Study
Initiated in 2009
Multinational trial: Early vs delayed ART initiation
1:1 Randomized Controlled Trial
Patients: HIV +, treatment nave, CD4 >500
Intervention: ART at study enrollment
Control: Defer ART until CD4
NEJM 2015; 373:795-807
HR of primary endpoint: 0.43 (p
Implications
AIDS and non-AIDS complications decreased by early
ART
Mortality difference not shown (p=0.13)
Strong data now exists to treat all HIV patients early
To prevent disease progression (and subsequent morbidity)
To prevent transmission (previous studies)
Community-Acquired Pneumonia Requiring
Hospitalization among U.S. Adults
Seema Jain, M.D., Wesley H. Self, M.D., M.P.H., Richard G. Wunderink, M.D., Sherene Fakhran, M.D., M.P.H., Robert Balk, M.D., Anna M. Bramley, M.P.H., Carrie
Reed, Ph.D., Carlos G. Grijalva, M.D., M.P.H., Evan J. Anderson, M.D., D. Mark
Courtney, M.D., James D. Chappell, M.D., Ph.D., Chao Qi, Ph.D., Eric M. Hart, M.D., Frank Carroll, M.D., Christopher Trabue, M.D., Helen K. Donnelly, R.N., B.S.N., Derek
J. Williams, M.D., M.P.H., Yuwei Zhu, M.D., Sandra R. Arnold, M.D., Krow Ampofo, M.D., Grant W. Waterer, M.B., B.S., Ph.D., Min Levine, Ph.D., Stephen Lindstrom, Ph.D., Jonas M. Winchell, Ph.D., Jacqueline M. Katz, Ph.D., Dean
Erdman, Dr.P.H., Eileen Schneider, M.D., M.P.H., Lauri A. Hicks, D.O., Jonathan A. McCullers, M.D., Andrew T. Pavia, M.D., Kathryn M. Edwards, M.D., Lyn
Finelli, Dr.P.H., for the CDC EPIC Study Team
N Engl J Med Volume 373(5):415-427
July 30, 2015
Community-Acquired Pneumonia Active Population-Based Surveillance
Cohort-type study
Goal: Define CAP- etiology + epidemiology
Setting: 3 Hospitals in Chicago and 2 in Nashville
Timeframe: 1/2010 through 6/2012
Patients: Hospitalized Fever/hypothermia; Leukopenia/Leukocytosis; AMS (surrogate)
Acute respiratory illness: Cough/CP/SOB/Respiratory failure
CXR: Consistent with PNA
What did they test?
Most patients:
Blood cultures
Urinary Antigens: S. pneumoniae/L. pneumophila
NP/OP PCR swabs (Viruses/Chlamydophila/Mycoplasma)
Sputum for culture (attempted) and L. pneumophila PCR
Some patients:
Pleural fluid PCR for most bacteria (GNRs, Strep/Staph)
BAL cultures
Paired serum serologies (respiratory viruses)
Jain, S et al, NEJM 2015 373(5):415-427
Jain, S et al, NEJM 2015 373(5):415-427
Pathogen Detection among U.S. Adults with Community-Acquired Pneumonia Requiring Hospitalization, 20102012.
Jain, S et al, NEJM 2015 373(5):415-427
The Missing 62 Percent
Most likely sources of the missing 62%
Large amount of wrong diagnosis
CHF, COPD exacerbations/bronchitis, poor films, atelectasis etc.
Poor specimens/missing specimens
NP/OP submitted from 98%
Blood cultures from 91%
Urine Ag from 85%
41% had a sputum submitted
12% had a high-quality sputum submitted
Nearly all patients had antibiotics before sputum collected
Supplementary Data
Jain, S et al Accessed NEJM.org
Take Home: CAP in 2016 and Beyond
Streptococcus pneumoniae may be less common than before
Likely due to vaccinating children with a good vaccine
PCV7 ~2000, PCV 13 ~ 2008
Whether vaccinating adults > 65 years will make a difference is unclear
Pre-treatment with antibiotics and poor sputum specimen
collection may cause us to underdiagnose bacterial causes
Viruses cause a significant amount of pneumonia
Including rhinovirus
Newer diagnostics (non-culture related) may help
Implementation/bundling strategies required to make this useful
(keep patients safe, decrease antibiotic use, optimize costs, etc.)
Vertebral Osteomyelitis (OM)
Duration of antibiotics not well studied in the past
Considerable variability in practice
French RCT (open label) designed to test duration
71 hospitals
Patients: OM of spine due to bacteria (no hardware)
Intervention: 6 weeks of antibiotics (IV and po)
Control: 12 week of antibiotics (IV and po)
Outcome: Cure at 1 year (No fever/pain and low CRP);
QOL secondary outcome
Bernard, L et al Lancet 2015; 385:875-82
Take home: Vertebral OM
Nearly identical results with both length regimens
Extra 6 weeks does not appear to be useful
Quality of life also did not differ
90% effective
~50% getting 2 weeks or less of IV, followed by oral
Very little MRSA (8/145)
High usage of fluoroquinolone + rifampin (less common in US)
Ok for 6 weeks total, may be able to use less IV
Long term outcome is good, but patients do not feel
better at the end of antibiotics
Antibiotics for Intra-abdominal Infections
Guidelines suggest 4-7 day of therapy
Often patients are on 14 days or more of antibiotics
High rates of complications
Lack of good data whether longer therapy can prevent them
Trial of Short-Course Antimicrobial Therapy for Intraabdominal Infection
(A.K.A. STOP-IT)
Robert G. Sawyer, M.D., Jeffrey A. Claridge, M.D., Avery B. Nathens, M.D., Ori D. Rotstein, M.D., Therese M. Duane, M.D., Heather L. Evans, M.D., Charles H.
Cook, M.D., Patrick J. ONeill, M.D., Ph.D., John E. Mazuski, M.D., Ph.D., Reza
Askari, M.D., Mark A. Wilson, M.D., Lena M. Napolitano, M.D., Nicholas Namias, M.D., Preston R. Miller, M.D., E. Patchen Dellinger, M.D., Christopher M. Watson, M.D., Raul
Coimbra, M.D., Daniel L. Dent, M.D., Stephen F. Lowry, M.D., Christine S. Cocanour, M.D., Michaela A. West, M.D., Ph.D., Kaysie L. Banton, M.D., William G. Cheadle, M.D., Pamela A. Lipsett, M.D., Christopher A. Guidry, M.D., and Kimberley
Popovsky, B.S.N.
N Engl J Med Volume 372(21):1996-2005
May 21, 2015
Study to Optimize Peritoneal Infection
Therapy (STOP-IT)
Inclusion criteria:
Age 16 years.
Hospitalized for
