Infectious Disease (ALERT) Updates
By Carol A. Kemper, MD, FACP
Hung Y-P, et al. Clinical impact of Clostridium difficile colonization. J Microbiol Immunol Infect 2014; http://dx.doi.org/10.1016/j.jmii/2014.04.11; and Alasmari F, et al. Prevalence and risk factors for asymptomatic Clostridium difficile carriage. CID 2014;59(2):216-222.
Asymptomatic carriage of C. difficile in adult hospitalized patients varies regionally, but estimates suggest that 4% to 23% of patients being admitted to hospital in the U.S. may be colonized with toxogenic strains of C. difficile (TCD). Not only are these patients at risk for active C. difficile infection (CDI), they are a significant source for skin and environmental contamination, similar to patients with active CDI. Some experts have advocated for greater attention to individuals admitted to hospital with asymptomatic C. difficile colonization, although no formal guidelines advocate for such. In addition, while treatment of these asymptomatic patients with metronidazole or vancomycin is not supported by current evidence, some physicians presumptively "prophylax" these individuals with metronidazole or vancomycin, especially when administering other antimicrobials, presuming the risk of active CDI is not trivial.
Because surveillance is not inexpensive, screening efforts should focus only on persons at high risk for C. difficile carriage. In an attempt to define those risk factors, Alasmari et al. screened 259 patients being hospitalized at Barnes-Jewish Hospital from 2010-2011. Forty (15%) were colonized with toxogenic strains of C. difficile (TCD) and 15 (6%) had non-toxogenic strains. Comparing these two groups, rates of recent hospitalization (50% vs 50%) and recent antibacterial exposure within 90 days (55% vs 56%) were similar; although admission from a SNF or other health-care facility was slightly greater for those with TCD strains than those with non-TCD (33% vs 24%). One or more outpatient clinic visits were documented within 30 days of hospitalization for 85% of those with TCD, and 20% were on hemodialysis (compared with only 3.9% of non-colonized patients). There was considerable strain heterogeneity, and only 1 (3%) of those with TCD strains was found to have ribotype 027.
As the result of this and other similar data, our hospital facility has been performing surveillance rectal swabs for CD PCR for more than one year, placing any positives in contact isolation. The results are available twice daily. Surveillance was initially limited to those being directly admitted from a SNF or outside health care facility, but has been expanded to include: (1) any residence at a SNF, rehab, outside health care facility, or our own hospital within 30 days; (2) hemodialysis; and (3) a prior history of CDI at any time. It is estimated that up to 14% of persons with active CDI may remain colonized and continue to shed organisms for up to one year.
Rates of asymptomatic carriage at our facility are tracking at about 11% (informal data for the previous 6 months, 59/557 positive PCRs for TCD). Most of the positives are admitted from SNFs or other health care facilities. Approximately 250 persons are screened per quarter, for an estimated cost to the hospital of $20,000 quarterly — less than the estimated cost to the hospital of a single episode of CDI. Tacquired." In a twist of modern health care semantics, 2-3 of the active CDI cases identified per month were previously identified as being carriers, and thus no longer "count" as hospital-onset (HO)-CDI for reporting purposes. Over the past 3 years, rates of HO-CDI have steadily dropped at our facility — finally reaching our goal this year, well worth the cost. Now, if we only knew what to do medically with the positives.
ASM and CLSI White Paper on MSSA and Ceftriaxone Etests. July 11, 2104: http://bit.ly/1A0eJyB
Cefriaxone is one of those rare work horse antibiotics — one of the few antibiotics I reached for 30 years ago as an intern, and continue to use daily. It covers all manner of ills, is well tolerated, even at higher dosages, requires no specific monitoring or renal dose adjustment, and is generally administered once a day. From an ID perspective, it doesn’t get any better.
Recent data has, however, raised concerns that Ceftriaxone may be losing it’s grip on MSSA, as some studies have suggested an upward trend in MICs for MSSA. This has led some experts to recommend against the routine use of Ceftriaxone for the treatment of more severe MSSA infections, such as endocarditis or joint infection, at least not before confirming susceptibility. But most clinical laboratories do not routinely perform CFTX MICs to staphylococci; and oxacillin is ordinarily used to indirectly predict cephalosporin susceptibility. Furthermore, even if an Etest for CFTX MIC for an MSSA isolate is obtained there are no current CLSI criteria for CFTX breakpoints for staphylococci. The 2012 CLSI M100 breakpoint previously used for defining susceptibility was < 8 mcg/ml, 16-32 mcg/mL (intermediate), and > 64 mcg/ml (resistant). In contrast, the Food and Drug Administration (FDA) susceptible breakpoints are < 4 mcg/mL (susceptible), 8 mcg/mL (intermediate), and > 16 mcg/mL (resistant).
Adding to the confusion, a recent article (Pickering et al.) first published in CID (online March 14, 2014) stating that MSSA isolates at their community teaching facility were 60% resistant to ceftriaxone has been retracted due to an honest error in interpretation of a key laboratory test. The data presented were obtained using Etest ceftriaxone strips (which are not FDA-cleared for testing of staphylococci). The CDC since obtained 16 of the MSSA isolates from the Pickering study, which were tested using broth microdilution and disk diffusion, and also with two different strip Etests. All of the isolates tested CFTX-susceptible by both broth microdilution (BMD) (MIC range, 2-4 mcg/mL) and disk diffusion (zone range 22-27 mm). In contrast, CFTX MICs obtained with the two E tests were generally higher than those obtained by BMD; 42% of the isolates tested by Etest demonstrated MICs of 16-32 mcg/mL — which would be presumed to be at least intermediate, if not resistant by Etest alone. Based on this and other data, the ASM has stated the Etest will overcall resistance of MSSA isolates, and is inadequate for testing staphylococci to CFTX.
So what’s an ID practitioner to do? Limited data suggest that CFTX may, in fact, be less bactericidal than either cefazolin or vancomycin in in vitro models. And there appears to be a strong inverse correlation between CFTX MICs and antibacterial activity. In a small in vitro model, bacterial killing at 24 hrs was reduced significantly for escalating CFTX MICs of 2, 4 and 8 mcg/mL. Available in vitro evidence suggests that CFTX may not be adequate in the treatment of serious MSSA infection when the MIC is > 2 mcg/ml -- but may be a very reasonable option at lower MICs, although there remains limited published clinical data demonstrating its efficacy in serious MSSA infection. But if the MIC can not readily be determined you may be stuck.
I believe that most clinicians are unaware of these concerns, and continue to broadly utilize CFTX for MSSA infection. Furthermore, the alternatives are not necessarily better, for other reasons -- While cefazolin is considered a first-line agent for treatment of MSSA bacteremia and bone and joint infection, it remains a second-line agent in current guidelines for endocarditis treatment and has poor CNS penetration
