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C Diff Higher Classification Essay

Know the risks and educate providers of the new specificity for coding recurrent.

For 2018, there is an important change in ICD-10 when assigning a diagnosis code for clostridium difficile (C. diff.) infection (CDI).

CDI Is a Significant Threat

Each year, healthcare treats close to 3 million episodes of CDI, an infection by an anaerobic, gram-positive, spore-forming bacillus, typically manifesting as enterocolitis with acute onset diarrhea, and possibly progressing to pseudomembranous colitis. Typically, it’s diagnosed with positive results from two primary reference tests — the C. diff. cytotoxin neutralization assay and toxigenic culture — after the onset of acute diarrhea, absent some other cause for the diarrhea. Nosocomial transmission is typically a function of environmental surface contamination and touch between staff and other patients. It’s also associated with antibiotic treatment or chemotherapy affecting the normal flora of the colon. CDI costs the healthcare system an estimated at $3.2 billion, annually.

As many as 20 percent of patients infected with C. diff. become sick again — either because the first bout never was eliminated or due to a different strain. After two or more bouts of the infection, the recurrence rate more than triples that number. The American College of Gastroenterology has defined recurrent CDI as an “episode of CDI that occurs eight weeks after the onset of a previous episode, provided the symptoms from the previous episode resolved.” The risk of recurrence is higher among patients who:

  • Are older than 65;
  • Are on an antibiotic regimen for an unrelated illness; or
  • Have a significant underlying disorder including malignancies, chronic kidney disease, and chronic liver disease.

The risks to the patient from subsequent bouts of CDI are higher than with the initial affliction.

The treatment regimens for recurrent CDI differ from the initial treatment. Treatment for the initial episode might include discontinuation of the inciting antibiotic regimen, metronidazole, and possibly vancomycin. Treatment for recurrent CDI might include a tapered or pulse vancomycin regimen, fidaxomicin, and fecal microbiotic transplant therapy. Research has been done on additional therapies, including use of bezlotoxumab alone or in combination with the drug actoxumab.

ICD-10 Adds Recurrent CDI in 2018 

CDI has been coded in ICD-10-CM at A04.7 Enterocolitis due to Clostridium difficile. The notes indicate this diagnosis code includes pseudomembranous colitis. Partly due to the higher morbidity of recurrent CDI and the different treatment regimens, the 2018 ICD-10-CM code set distinguishes between recurrent CDI and CDI not specified as recurrent at category code A04.7:

A04.71 Entercolitis due to clostridium difficile, recurrent

A04.72 Entercolitis due to clostridium difficile, not specified as recurrent

Educate providers of the new specificity for recurrent CDI. And remember there was a change to Section 1 of the 2017 ICD-10-CM Official Guidelines for Coding and Reporting to clarify the provider’s role:

Code Assignment and Clinical Criteria: The assignment of a diagnosis code is based on the provider’s diagnostic statement that the condition exists. The provider’s statement that the patient has a particular condition is sufficient. Code assignment is not based on clinical criteria used by the provider to establish the diagnosis.

Using the new codes allows better tracking of recurrent CDI, and may help with managed care pre-certification processes for alternative treatment regimens by identifying recurrent CDI.


Resources

Cole, Shola and Thos. J Stahl, “Persistent and Recurrent Clostridium difficile Colitis,” Clinics in Colorectal Surgery, Vol 28, no. 2, 2015, p. 65.

McFarland LV. “Emerging therapies for Clostridium difficile infections,” Expert Opin Emerg Drugs 2011; 16:425 – 39.

www.mayoclinic.org/diseases-conditions/c-difficile/diagnosis-treatment/treatment/txc-20202426

ICD-10 Coordination and Maintenance Committee Meeting, March 9-10, 2016, page 19:
www.cdc.gov/nchs/icd/icd10cm_maintenance.htm

www.cidrap.umn.edu/news-perspective/2017/01/new-treatment-recurrent-c-diff-shows-promise

William C. Fiala, MA, CPC, CCS-P, RMA, is a professor of practice in the School of Allied Health Technology, College of Health Professions, University of Akron. Beyond the academic setting, his business entity, the successor to a fee schedule calculation service incorporated in 1992, has provided coding audits, compliance help, and productivity analyses (wcfiala@sbcglobal.net).

Antimicrobial-Resistant Strains of Clostridium difficile from North America

ABSTRACT

A total of 316 toxigenic Clostridium difficile clinical isolates of known PCR ribotypes from patients in North America were screened for resistance to clindamycin, metronidazole, moxifloxacin, and rifampin. Clindamycin resistance was observed among 16 different ribotypes, with ribotypes 017, 053, and 078 showing the highest proportions of resistance. All isolates were susceptible to metronidazole. Moxifloxacin resistance was present in >90% of PCR-ribotype 027 and 053 isolates but was less common among other ribotypes. Only 7.9% of the C. difficile isolates were resistant to rifampin. Multidrug resistance (clindamycin, moxifloxacin, and rifampin) was present in 27.5% of PCR-ribotype 027 strains but was rare in other ribotypes. These results suggest that antimicrobial resistance in North American isolates of C. difficile varies by strain type and parallels rates of resistance reported from Europe and the Far East.

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INTRODUCTION

Clostridium difficile is a major health care-associated pathogen that is responsible for a wide spectrum of disease, ranging from mild diarrhea to life-threatening complications, such as pseudomembranous colitis and toxic megacolon (19). The severity and outcome of C. difficile infection (CDI) is influenced by a multiplicity of factors, including patient demographics, such as age and immune status, length of hospitalization, and, most of all, receipt of antimicrobial therapy (23, 25). Antimicrobial therapy, often given for treatment of other infectious diseases, can render the patient susceptible to CDI if the patient is exposed to a toxigenic strain of the organism. When CDI was first reported in the 1970s, prior use of clindamycin was established as a significant risk factor. However, by 1980, cephalosporins replaced clindamycin as the major risk factor (4). In the next 20 years, expanded- and extended-spectrum cephalosporins became associated with a high risk of CDI (6). More recently, fluoroquinolones have been linked to CDI and to severe epidemics, particularly those caused by PCR-ribotype 027 (27). Between 5% and 30% of patients receiving antimicrobial agents may develop health care-associated diarrhea, with C. difficile causing up to 30% of those cases (22). Antimicrobial stewardship programs can assist in curtailing these selective pressures (17, 18). The emergence of C. difficile strains that are resistant to multiple antimicrobial agents can complicate prevention programs and potentially, in the case of metronidazole, treatment (13). Thus, knowing the prevalence of antimicrobial-resistant strains in an institution can be helpful for optimizing antimicrobial stewardship programs.

(These data were presented in part at the 111th General Meeting of the American Society for Microbiology, 21 to 24 May 2011, New Orleans, LA.)

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MATERIALS AND METHODS

Bacterial isolates.A total of 316 toxigenic clinical isolates of C. difficile were received from 7 hospitals in the United States (including hospitals located in California, Illinois, Indiana, North Carolina, and Washington) and Canada (Quebec) during 2008 and 2009. These isolates have been described elsewhere (32). Organisms were isolated using broth-enrichment toxigenic culture and typed by PCR-ribotyping (PCR-R), pulsed-field gel electrophoresis (PFGE), and restriction endonuclease analysis of whole-cell DNA (REA). The isolates were preserved at −80°C in 15% glycerol-Brucella broth and were subcultured twice on prereduced anaerobically sterilized (PRAS) Brucella blood agar (Anaerobe Systems, Morgan Hill, CA) prior to antimicrobial susceptibility testing.

Antimicrobial susceptibility testing.Isolates were tested for susceptibility to clindamycin, metronidazole, moxifloxacin, and rifampin using Etest strips (bioMérieux, Marcy-l'Étoile, France), as described in the Etest technical guide. The MIC results were rounded up to the next doubling dilution and interpreted using Clinical and Laboratory Standards Institute (CLSI) breakpoints for susceptibility testing of anaerobic bacteria (8). Individual colonies from 24- to 48-h Brucella blood agar plates were suspended in Brucella broth to the turbidity of 1.0 McFarland standard, and the inoculum was applied to 150-mm Brucella blood agar plates (Anaerobe Systems, Morgan Hill, CA). Plates were incubated anaerobically at 35°C in a Bactron anaerobic chamber (Sheldon Manufacturing Inc., Cornelius, OR). MICs were read and recorded at 24 h, and clindamycin results were confirmed after 48 h of incubation to ensure detection of inducible resistance (as per the Etest package insert). Bacteroides fragilis ATCC 25285, Bacteroides thetaiotaomicron ATCC 29741, and Eubacterium lentum ATCC 43055 were used for quality control (9). All control results were within acceptable ranges.

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RESULTS

The MIC50 and MIC90 results for clindamycin, metronidazole, moxifloxacin, and rifampin when tested against 316 C. difficile strains are presented in Table 1. Clindamycin resistance was present in 41.5% of isolates, while moxifloxacin resistance was present in 38.0% of isolates; only 7.9% of isolates were resistant to rifampin. All isolates were susceptible to metronidazole. There were no inner colonies suggestive of heteroresistance within the zones of inhibition around the metronidazole Etest strips. Table 2 shows the MIC data for the seven most common PCR ribotypes observed among the study isolates. Moxifloxacin resistance was present in >90% of PCR-ribotype 027 and 053 isolates but was less common among other ribotypes (Fig. 1). Clindamycin resistance was observed among several ribotypes, with ribotypes 017, 053, and 078 showing the highest proportions of resistance (100%, 91.7%, and 71.4%, respectively). Rifampin resistance (MIC ≥ 32 μg/ml) was observed in 27.5% of ribotype 027 isolates and sporadically among ribotypes 017 and 012 isolates (Fig. 1). Overall, 27.5% of ribotype 027 isolates were resistant to clindamycin, moxifloxacin, and rifampin. This multidrug resistance pattern was also observed among several isolates of ribotype 017.

Fig 1

Proportions of antimicrobial resistance among 307 isolates of C. difficile according to their PCR ribotypes. The graph excludes a total of nine isolates of PCR ribotypes 003 and 075 for which no resistance was observed.

A comparison of the proportions of resistance observed in this study and those reported in 15 other studies of C. difficile resistance is shown in Table 3. Moxifloxacin resistance ranged from 2 to 87%. A report of 82% resistance was from a single site, where 69% of isolates were pulsed-field gel electrophoresis types NAP1 or NAP2 (7). Clindamycin resistance ranged from 15 to 97% (the latter in a study of 1,613 isolates from Scotland). Rifampin resistance was reported infrequently, and only a single metronidazole-resistant isolate was reported in these other studies.

Table 1

MIC range, MIC50, and MIC90 for antimicrobial agents tested against 316 C. difficile isolates

Table 2

MIC range, MIC50, and MIC90 among isolates of the seven most frequent PCR ribotypes

Table 3

Published reports of antimicrobial resistance rates in C. difficilea

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DISCUSSION

Multidrug resistance (i.e., resistance to clindamycin, moxifloxacin, and rifampin) was present in 22 of 80 (27.5%) C. difficile PCR-ribotype 027 isolates from the United States and Canada but was unusual among other ribotypes (Fig. 1). All rifampin-resistant strains were also resistant to clindamycin and moxifloxacin. This is in contrast to the report of Curry et al. (12), in which 81.5% of ribotype 027 isolates from a hospital in Pittsburgh were resistant to rifampin. The range of antibiograms observed in our study indicates that not all ribotype 027 isolates, which were obtained from seven laboratories across the United States and Canada, are clonal. This is consistent with the data presented by Killgore et al. (20), which indicated that subtypes could be defined within ribotype 027 isolates by other typing techniques. Unfortunately, rifampin resistance is rarely reported in other resistance surveys of C. difficile isolates, limiting comparisons to other data sets (Table 3). Although clindamycin and moxifloxacin resistance were both relatively common among our isolates (41.5% and 38.0% of isolates, respectively), clindamycin resistance was observed in all but two of the 16 ribotypes in our study (where there were at least 4 isolates of that ribotype tested), while moxifloxacin resistance was limited to 10 strain types. Yet, only in ribotype 053 isolates did the two resistances appear tightly linked (i.e., both were present in 11/12 isolates). The ribotype 053 strains came from four different laboratories located in California, Indiana, Illinois, and North Carolina and thus did not appear to be associated with a clonal outbreak of CDI. Overall, though, no resistance pattern was consistent enough to be a useful strain marker.

A review of antimicrobial resistance among C. difficile isolates by Huang et al. in 2009 (15) did not contain data specifically on ribotype 053 strains but did confirm high rates of clindamycin resistance in a variety of ribotypes, including ribotype 017 isolates from Europe (there were no data on ribotypes 012 or 046 reported). Among other surveys of C. difficile resistance not covered by Huang et al. (i.e., those cited in Table 3), only 7 of 15 reports showed higher rates of moxifloxacin resistance than was observed in our study, but 11 of 15 showed higher rates of clindamycin resistance. PCR ribotype 001 was the most common ribotype reported in these surveys, followed by ribotypes 014, 027, and 106. Modest levels of resistance were seen among our isolates of these ribotypes as well.

Resistance to the antimicrobial agents most commonly used to treat C. difficile infections, i.e., vancomycin and metronidazole (5, 10), is reported rarely in the literature (15). However, both metronidazole heteroresistance (26) and reduced susceptibility to metronidazole have been reported (2). We did not observe either of these phenomena in our study, but this may have been due to the limited number of medical centers that contributed isolates to this study.

In summary, while resistance to clindamycin and moxifloxacin is widespread in C. difficile isolates from North America, multidrug resistance (i.e., resistance to clindamycin, moxifloxacin, and rifampin) was limited primarily to ribotype 027 isolates. Although these antimicrobial agents are not used for therapy (with the possible exception of rifaximin, which is in an antimicrobial agent class related to rifampin), they may still play a key role in enabling patients taking these antimicrobial agents to become colonized and infected with C. difficile if exposed to these resistant strains (11).

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ACKNOWLEDGMENTS

We thank Ellen Jo Baron and Diane Citron for helpful comments.

F.C.T., I.A.T., and D.H.P. are employees and shareholders of Cepheid. Funding for this study was provided by Cepheid.

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FOOTNOTES

    • Received 27 January 2012.
    • Returned for modification 18 February 2012.
    • Accepted 4 March 2012.
    • Accepted manuscript posted online 12 March 2012.
  • Address correspondence to Fred C. Tenover, fred.tenover{at}cepheid.com.

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