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ON-DEMAND
A Quarterly Publication by Cepheid
REPORT
Volume 1, Issue 3
IN THIS ISSUE…
Cover Story:
A New Paradigm for the Management
of Skin and Soft Tissue Infections
(SSTI) in the Era of MRSA
Inside:
Highlights from ICAAC/IDSA
a Summary of Selected
Presentations with a Focus on
Healthcare-Associated Infections
Online:
www.cepheidondemand.com
CEPHEID
ON-DEMAND Rapid Testing, a New Paradigm Affecting
Executive Editor
David Persing, M.D., Ph.D. prescribing antimicrobials) has been at physician who saw that patient is no
Managing Editor least one publicized approach to such longer responsible for the care of that
Stripe Demarest situations.1 And in fact, in most cases patient. So either that physician must
Lead Author (90.5% in one study), the patient with- attempt to contact the patient on his
Ellen Jo Baron, Ph.D. out other risk factors does well with day off, or an ED nurse, with many
drainage alone.2 other more pressing tasks, must spend
Contributing Author
precious time trying to locate and
Fred Tenover, Ph.D But wouldn’t it be helpful to know the speak with the patient. If the lesion has
Production Manager identity of the offending organism? healed properly, the patient may not
Gregory Birgfeld If infected patients knew that their appreciate the call.
infection was caused by the infamous
Newsletter Design
Bijal Patel methicillin-resistant Staphylococcus What if the infection is severe enough
aureus (MRSA), for example, they might that the patient is admitted to the hos-
Print/Web Design &
take precautions to avoid reinfection, pital? Of course cultures will be obtained.
Production
Tori Muir or they might modify their personal If the cultures show the patient is
hygiene practices to prevent spread- infected with MRSA, then the patient is
ing the infection to family members, placed on contact precautions or moved
friends, or close contacts. to a private room—but this information
REPORT isn’t available for at least two days.
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Cepheid On-Demand Report
This test offers an exciting new option Patient presents with signs/
symptoms of skin infection:
Is the lesion purulent (i.e., are any
of the following signs present)?
Possible cellulitis without abscess:
• Provide antimicrobial therapy
for diagnosing infections rapidly and • Redness • Fluctuance—palpable fluid-filled with coverage for Streptococcus
accurately. If surgeons knew that a • Swelling
• Warmth
YES cavity, movable, compressible
• Yellow or white center
NO spp. and/or other suspected
pathogens
patient’s wound was infected with • Pain/tenderness • Central point or “head” • Maintain close follow-up
• Complaint of “spider bite” • Draining pus • Consider adding coverage for
MSSA and not MRSA, they could be • Possible to aspirate pus with MRSA (if not provided initially),
needle and syringe if patient does not respond
confident that their cephalosporin or
extended-spectrum penicillin therapy YES
Clindamycin • FDA-approved to treat serious infections • Clostridium difficile-associated disease, while uncommon,
due to S. aureus may occur more frequently in association with clindamycin
The most widely used algorithm for • D-zone test should be performed to compared to other agents.
identify inducible clindamycin resistance in
SSTIs today is the one developed by erythromycin-resistant isolates
rithm for presumptive treatment of Rifampin • Use only in combination with other agents. • Drug-drug interactions are common.
Linezolid • Consultation with an infectious disease • Has been associated with myelosuppression, neuropathy and
MRSA. Figure 2 provides an often-used specialist is suggested. lactic acidosis during prolonged therapy.
• FDA-approved to treat complicated skin in‑
algorithm for pediatric patients pres- fections, including those caused by MRSA.
ents more details on the lesion size • MRSA is resistant to all currently available beta-lactam agents (penicillins and cephalosporins)
• Fluoroquinolones (e.g., ciprofloxacin, levofloxacin) and macrolides (erythromycin, clarithromycin, azithromycine) are not optimal
and location.9 Using these references for treatment of MRSA SSTIs because resistance is common or may develop rapidly.
as guidelines, our panel had a free- * Data from controlled clinical trials are needed to establish the comparative efficacy of these agents in treating MRSA SSTIs.
Patients with signs and symptoms of severe illness should be treated as inpatients.
flowing discussion about how the use of ** Consult product labeling for a complete list of potential adverse effects associated with each agent.
See RAPID TESTING on next page Figure 1. Treatment algorithm flowchart based on CDC guidelines.
3
December – February 2008 – 2009
OUTPATIENT INPATIENT
Culture & susceptibility
(very important) Clindamycin 30–40
Empiric therapy Clindamycin 20–30 mg/kg/day IV; if
mg/kg/day PO life-threatening, add Vanco-
mycin 40 mg/ kg/day IV
Positive culture
Staph or Strep?
Penicillin + clindamycin in
Strep. pyogenes Penicillin severe soft-tissue
Staph. aureus (group A streptococcus) infections
Methicillin/oxacillin
susceptibility
Cephalexin or dicloxicillin Nafcillin 150–200
Sensitive (MSSA) mg/kg/day; D/C vancomy-
Resistant (MRSA) 50–75 mg/kg/day
cin and/or clindamycin
Clindamycin susceptibility
Trimethoprim- Vancomycin 40 mg/kg/day
Resistant sulfamethoxazole or IV; potential role for linezolid,
Susceptible
linezolid, if susceptible other agents
Erythromycin susceptibility
Continue clindamycin and/or
Susceptible Continue clindamycin vancomycin, depending on
Resistant (inducible resistance to site & severity of infection
clindamycin is possible)
Negative
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Cepheid On-Demand Report
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December – February 2008 – 2009
• Overall, the algorithms were presence of S. aureus would suggest with skin and soft tissue infections
appropriate except that instead of use of cephalexin, nafcillin, or other who harbored either S. aureus or MRSA.
suspicion of MRSA triggering the use anti-S. aureus antibiotics. These distinguished clinicians antici-
of anti-MRSA therapy, the actual pate a new era in which more rapid
presence of MRSA would do so. Given In summary, our panel of experts information will lead to better initial
the excellent predictive value of expressed great enthusiasm for the treatment choices.
negative results (as seen in beta trials), ability to quickly identify those patients
Cephalexin Cephalosporin - oral Also has anti-streptococcal activity; should be considered when cellulitis is present
Anti-MSSA
Doxycycline Tetracycline - oral May have side-effects; not for use in children <5 years of age
or IV
Minocycline Tetracycline - oral Under-appreciated agent; similar to tetracycline
or IV
Vancomycin Glycopeptide - May be less effective than other agents, particularly for bloodstream infections; levels should
oral or IV be monitored; overutilization can contribute to development of VRE; CDC recommends ef‑
forts to reduce use of vancomycin; recent studies suggest mean MRSA vancomycin MICs
are increasing
Daptomycin Lipopeptide - IV Effective against MRSA; not active in respiratory tract; more expensive than other agents
Oritavancin Lipoglycopeptide - IV New agent currently in clinical trials; appears to have excellent anti-MRSA activity
Ceftobiprole Cephalosporin – IV New extended spectrum cephalosporin that has anti-MRSA activity
References 7. Kirkland KB, Weinstein JM. Adverse effects of contact isolation. Lan-
cet. 1999; 354(9185):1177–1178.
1. Chambers, Moellering. Clinical Decisions: Management of Skin
and Soft-Tissue Infection. New England Journal of Medicine. 2008; 8. Ruhe JJ, Smith N, Bradsher RW, Menon A. Community-Onset
359(10):1063–1065. Methicillin-Resistant Staphylococcus aureus Skin and Soft-Tissue
Infections: Impact of Antimicrobial Therapy on Outcome. Clinical Infec-
2. Rajendran PM, Young D, Maurer T, et al. Randomized, double-blind, tious Diseases. 2007; 44:777–784.
placebo-controlled trial of cephalexin for treatment of uncomplicated
skin abscesses in a population at risk for community-acquired meth‑ 9. Lee, MC, Rios AM, Aten MF, Mejias A, Cavuoti D, McCracken GH Jr,
icillin-resistant Staphylococcus aureus infection. Antimicrob Agents Hardy RD. Management and outcome of children with skin and soft
Chemotherapy. 2007; 51:4044–8. tissue abscesses caused by community-acquired methicillin-resistant
Staphylococcus aureus. Pediatric Infectious Disease Journal. 2004;
3. Huang SS, Platt R. Risk of Methicillin-Resistant Staphylococcus aureus 23(2):123–7.
Infection after Previous Infection or Colonization. Clinical Infectious
Diseases. 2003; 36:281–5 10. Huang SS, Datta R, Platt, R. Risk of Acquiring Antibiotic-Resistant
Bacteria From Prior Room Occupants. Archives of Internal Medicine.
4. Bonness S, Szekat C, Novak N, Bierbaum G. Pulsed-Field Gel Elec‑ 2006; 166:1945–1951.
trophoresis of Staphylococcus aureus Isolates from Atopic Patients
Revealing Presence of Similar Strains in Isolates from Children and 11. Stevens DL, Ma Y, Salmi DB, McIndoo E, Wallace RJ, Bryant AE.
Their Parents. Journal of Clinical Microbiology. 2008; 46:456–461. Impact of antibiotics on expression of virulence-associated exotoxin
genes in methicillin-sensitive and methicillin-resistant Staphylococcus
5. Lu P-L, Tsai J-C, Chiu Y-W, Chang F-Y, Chen Y-W, Hsiao C-F, Siu LK. aureus. Journal of Infectious Diseases. 2007; 195(2):202–11.
Methicillin-resistant Staphylococcus aureus carriage, infection and
transmission in dialysis patients, healthcare workers and their family 12. Forrest GN, Mehta S, Weekes E, Lincalis DP, Johnson JK, Venezia RA.
members Nephrol Dial Transplant. 2008; 23:1659–1665. Impact of rapid in situ hybridization testing on coagulase-negative
staphylococci positive blood cultures. Journal of Antimicrobial Chemo-
6. Hammond SP, Baden LR: Management of Skin and Soft-Tissue therapy. 2006; 58:154–158.
Infection — Polling Results. New England Journal of Medicine. 2008;
359:e20.
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Cepheid On-Demand Report
The American Society for Microbiology’s led to a statistically significant reduction were plated to the same 3 agars. In Phase II,
Interscience Congress on Antimicro- in hospital acquisitions of colonizing MRSA. the second swab was vortexed in sterile saline,
During the time of culture surveillance 30.4% and inoculated onto the 3 agars and into 6.5%
bial Agents and Chemotherapy and the of MRSA-colonized patients developed an and 3.25%NaCl TSBs. Broths were subcultured
Infectious Diseases Society of America’s MRSA infection, whereas during PCR-based if direct plating did not yield MRSA.
annual meeting were combined and held testing, only 9.1% of MRSA-positive patients In Phase I, direct plating recovered 68% of
developed MRSA infection. They concluded those with positive results in the Xpert MRSA
in Washington, DC this October. More
that PCR-based testing enhanced infection test. Seven more MRSA were recovered from
than 14,000 attendees acquired the control measures for MRSA. TSB subcultures (total 76% recovery). However,
latest information on new diagnostics, 13 of 21 MRSA culture negative samples grew
new therapies, microbial pathogen- K-3367. A Pilot Study of Active Surveillance MSSA. In Phase II, cultures overall yielded 87%
for MRSA by PCR on Admission to ICUs at a on blood agar and 92-93% on CHROMagars. Of
esis, and more. Here is a summary of a Tertiary Care Center 20 MRSA-negative cultures , 13 grew MSSA. The
few abstracts whose findings focus on Espinoza C, Fisher V, Jean W, Gaines B, Davis K, MSSA isolates were further characterized; 2/3
healthcare-associated infections. Wanger A, Schaeffer M, Ostrosky-Zeichner L were found to have a deletion in the mecA re-
Mem. Hermann TX Medical Ctr., Houston, gion. The isolation of MRSA from PCR-positive
performed the BD GeneOhm assay once daily patients was increased 10% by vortexing swabs
The majority of recent studies are
on all patients admitted to the adult ICU. in saline before plating and 7% by enriching
proving that infection control based Patients were initially all placed on modified overnight in TSB. These results further support
on surveillance is cost-effective and contact precautions and positive patients the superior sensitivity of molecular methods
beneficial, even when surveillance is were placed on full contact precautions and for detection of MRSA colonized patients.
flagged for future infection control actions.
restricted to limited inpatient units.
During the 3-month intervention period, D-1136. Surveillance Swabs for Detection of
11.6% of patients tested were MRSA positive. Methicillin-Resistant Staphylococcus aureus
C2-106. Detection of Oxacillin/Methicillin
There was a statistically significant decrease (MRSA): Diagnostic Yield of Different Ana-
Resistant and Susceptible Staphylococcus
in healthcare-associated ventilator-associ- tomic Sites and Comparison of Provider and
aureus by Culture and RT-PCR in Patients
ated pneumonias and bloodstream infections Patient-Collected Samples
Scheduled for Orthopedic Surgery
overall in the ICU, from 59 to 38 per 1000 ad- Lautenbach E, Fishman N, Nachamkin I, Hu B,
Halstead DC, Kirspel CE, Mckean KA, Meyer KS,
missions. MRSA infections dropped from 9% Tolomeo P, Prasad P, Bilker W, Zaoutis T
Boland BJ
to 5%. Importantly, the authors extrapolated Using cultures, workers at the Univ. of
Nasal swabs from 275 patients scheduled costs to one year. Even considering the cost Pennsylvania (Philadelphia) compared swabs
for orthopedic surgery at Baptist Hospital of testing and isolation, the cost avoidance from different sites collected by healthcare
(Jacksonville, FL) were tested by CHROMagar associated with preventing healthcare-asso- workers and by the patients themselves. Axillae,
and BD GeneOhm MRSA in Phase I and another ciated infections by PCR screening and sub- nares, throat, perineum, and groin swabs were
137 patients by the Xpert™ MRSA test (using a sequent isolation was estimated at $567,000. evaluated. Patient-collected swabs compared
frozen swab obtained at the same time) during
favorably with professionally collected samples.
Phase II. Rates of positivity more than doubled What’s good and what’s disappointing The best agreement between patient- and
with the Xpert MRSA test. Both molecular
about the various surveillance methods? provider-collected samples was 95% for the
systems usually agreed. The authors concluded
groin. To achieve >90% detection of colonized
that molecular methods were more sensitive
D-1137. Comparison of Direct Plating and persons, >1 site had to be sampled. In this pop-
than culture and that the GeneXpert® System
Broth Enhanced Culture for Recovery of ulation, the best single sites were nares (84%
gave more rapid results with less hands-on
MRSA from PCR Positive Nasal Swabs sensitive) and throat (65% sensitive). Groin and
time than did the SmartCycler® System.
Vonrentzell JE, Schreckenberger PC perineum cultures were more likely to be posi-
tive in community-onset patients (81%) than
C2-1066. Real-Time PCR (RT-PCR) for To resolve discrepancies between positive Gen-
hospital-onset patients (41%). Nares, throat,
Methicillin-Resistant Staphylococcus aureus eXpert (Cepheid) MRSA results and negative
and groin together achieved 100% sensitivity
(MRSA) Detection: Implications in a Neonatal culture results, Loyola scientists evaluated en-
and either nares and throat or nares and groin
Intensive Care (NIC) Setting hanced culture methods for recovery of MRSA.
reached 91% sensitivity for recovery of MRSA.
Song X, Campos J, Short B, Singh N During Phase I, the second swab from
In 2005, National Childrens’ Hospital in Wash- patients whose first swab yielded a positive K-3355. A Targeted Approach to MRSA Colo-
ington DC tested for MRSA at admission and or inconclusive PCR was plated directly onto nization Screening Using a PCR Assay and
weekly thereafter using cultures. After they blood agar, two types of MRSA selective Multi-Site Sampling Strategy
switched to rt-PCR (GeneXpert, Cepheid) in CHROMagars and then incubated in 1 mL Metzger BS, Leung SS, Currie BP
2007 the incidence of MRSA increased from of 6.5% NaCl in trypticase-soy broth (TSB)
overnight. Broths from negative plate cultures Colleagues at Montefiore Medical Center
6.9% to 10.8%. This enhanced detection
in the Bronx increased the sensitivity of
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December – February 2008 – 2009
surveillance cultures almost 24% by collecting Admissions wards of two hospitals in Birming- test. All 25 MRSA and 7 MSSA were correctly iden-
swabs from axilla, nares, and groin vs. nares ham, UK. Double swabs were collected from tified by the Xpert test in 50 minutes. One blood
alone. 268 patients, of whom 21.3% were posi- patients in the wards and one swab was used culture (negative for S. aureus) was identified as
tive from at least one site: 17.2% nares, 10.1% for near-patient testing, the other was sent MRSA by the Xpert test.
axilla, and 13.4% groin, were evaluated. Target- to the central laboratory. Valid paired results The sensitivities of the Xpert test for blood
ing screening to those patients who had either were available for 735 swabs, 62 of which were cultures were 100% for MRSA and MSSA and
long-term care residence, a previous MRSA MRSA positive. There was 97.1% agreement. 99% for no S. aureus. Specificities were 99%
isolate, or antibacterial use within the last 6 Sampling errors were thought to account for MRSA and 100% for MSSA. Sensitivity of
months, yielded a sensitivity of 80.7% and the for all discrepancies. The results of tests the Xpert test for wounds culture-positive for
need to test 43.7% of admissions. By adding performed at the wards were available in ≤ 2 MRSA was 99%. Sensitivities for wounds yield-
the risk factor of hospitalization within the hours for 97.7% of the swabs collected. The ing MSSA and no S. aureus on culture were 91%
last 6 months, sensitivity increased to 91.2% authors said that the use of the GeneXpert and 79%; and specificities were all >91%. Of 80
with the need to screen 57.8% of admissions. System at the patient point of care dramati- MRSA cultured from 235 wound swabs, the Xpert
They concluded that a targeted approach to cally reduced the time to result compared with test correctly identified 79. The Xpert MRSA/SA
surveillance and a two-swab (nares and skin) testing in the laboratory. test correctly identified 30 of 33 MSSA isolates
sample could result in near-complete capture from wounds; 2 were incorrectly called MRSA,
of MRSA-colonized patients. Late Breaker: First look at the new Xpert and one was not detected.
MRSA/SA test for SSTI and blood cul- From 122 wound cultures where no S. aureus
Use of PCR as a point-of-care test: at were isolated, the Xpert test detected MRSA
ture broths.
this time, there is only one moderate in 12 samples and MSSA in 14 samples. Because
complexity PCR assay FDA-cleared for D-2250a. Automated PCR to Detect Meth- resolving tests were not performed, the true
icillin-Resistant (MR) or -Susceptible (MS) nature of the discrepant results is not known
use in the United States.
Staphylococcus aureus (SA) in Blood Cultures yet. Dr. Musher suggested that previously
(BC) and Wound Swabs (WS) treated patients may account for some of the
D-1139. Potential Use of the Cepheid Xpert™
MRSA Test for Near-Patient Testing Musher DM, Goebel M, Matloobi M, Stager C, inconsistencies.
Brenwald NP, Baker N, Oppenheim B Parta M
Computer-interfaced Cepheid GeneXpert® 132 blood cultures yielding gram-positive cocci
Systems were installed in the Critical Care and in clusters were tested using the Xpert MRSA/SA
A Quarterly Publication
ON-DEMAND REPORT
Volume 1, Issue 3
CEPHEID