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Multi-drug Resistance

January 21, 2020

For the 2020 ICD-10-CM, new codes were created to capture antibiotic resistance in clinical settings. The intent is to identify antibiotic resistance in the U.S. for our health care database. There are multiple databases both public and private brought together by AHRQ under the Healthcare Cost and Utilization Project (HCUP). The National (Nationwide) Inpatient Sample (NIS) is the largest publicly available all-payer hospital inpatient care database in the United States. Researchers and policymakers use NIS data to identify, track, and analyze trends in health care utilization, access, charges, quality, and outcomes.  

Multidrug-resistant (MDR) infections are associated with increased mortality, length of stay, and hospital costs. MDR is defined as organisms with resistance to one or more antibiotics in three or more antibiotic/antimicrobial drug classes. To identify multidrug resistance, clinicians should have a working knowledge of the drug class of commonly used antibiotics and antimicrobials reported on culture sensitivity testing.

Methicillin-resistant Staphylococcus aureus (MRSA) accounts for up to 80% of bacterial MDR infections. Other commonly encountered MDR bacteria are vancomycin-resistant enterococci (VRE), Acinetobacter, Klebsiella, Pseudomonas, and coliforms, particularly E. coli and Clostridioides (formerly Clostridium) difficile.

MDR tuberculosis infection is increasingly common and particularly worrisome because many strains are resistant to all known antitubercular drugs. MDR Candida are also becoming problematic. Parasites and many viral pathogens are also becoming resistant to many antimicrobials.

High-risk MDR circumstances (Table 2) include immunosuppression from any cause, history of an MDR infection, known colonization by an MDR organism, and exposure to an MDR-infected person even at home. Structural lung disease, as in cystic fibrosis and bronchiectasis, is typically associated with Pseudomonas colonization and pneumonia, often with multi-drug resistance.

The three most common inpatient situations associated with multi-drug resistance are ventilator-associated pneumonia (VAP), catheter-related bloodstream infection (CRBSI), and catheter-associated urinary tract infection (CAUTI).

The new Category Z16 was created for the new drug resistance codes identifying the antibiotics to which the infectious organism is resistant (Table 3). The codes do not require the clinical MDR definition of resistance to 3 or more classes of antibiotics. In most cases, the codes specify an entire class of drugs keeping in mind there may be only a single drug in a class like vancomycin and clindamycin.

The provider must document the drug resistance in the record. If the provider documents resistance to multiple drug classes, a code is assigned for each of the drugs identified. If only “multi-drug resistance” is documented, code Z16.24 (multidrug resistance) is assigned.  Category Z16 codes are classified as CCs but not assigned to an HCC.

It’s the coder’s responsibility to assign a code for the correct drug class based on the antibiotics specified. For example, if the clinician documents resistance to gentamicin based on sensitivity testing, the coder must know that the aminoglycoside code (Z16.29) should be used. Table 1 should be helpful but coding software ought to lead the coder from a specific antibiotic to the correct drug-class code.

The type of infection is coded first, followed by a code for the organism—unless the infection code itself describes the organism (e.g. code J13, pneumococcal pneumonia)—and then the drug resistance code. In the case of MRSA, a drug resistance code is not assigned because the infection code identifies the antibiotic. In contrast, codes for infections caused by other drug-resistant organisms do not include the drug and require the additional Z16 code. For example, VRE sepsis is coded A41.81 (sepsis due to enterococcus) + Z16.21 (resistance to vancomycin).

Table 1. Antibiotic drug classes 

  • Aminoglycosides (gentamicin, tobramycin)
  • Penicillins (amoxicillin, nafcillin, oxacillin, piperacillin)
  • Cephalosporins (ceftriaxone, cefazolin, cefepime, ceftazidime, cefuroxime)
  • Carbapenems (imipenem, ertapenem, meropenem)
  • Fluoroquinolones (ciprofloxacin, levofloxacin)
  • Folate inhibitors (sulfamethoxazole/trimethoprim)
  • Glycopeptides (vancomycin)
  • Lincosamides (clindamycin)
  • Macrolides (azithromycin, clarithromycin)
  • Monobactams (aztreonam)
  • Nitrofurans (nitrofurantoin)
  • Tetracyclines (doxycycline, minocycline)
  • Azoles (fluconazole, itraconazole)
  • Echinocandins (micafungin)
  • Nitroimidazoles (metronidazole)
  • Polyenes (amphotericin B)

Source: CDC. Antimicrobial Use and Resistance (AUR) Module—Appendix B.

Table 2. Circumstances posing high risk of multi-drug resistance (MDR)

  • Immunosuppression from any cause
  • History of MDR infection
  • Known MDR colonization
  • Recently hospitalized (especially in ICU)
  • Recent antibiotic therapy (especially broad-spectrum)
  • Structural lung disease as in cystic fibrosis and bronchiectasis
  • Direct exposure to another person's MDR infection

Derived from multiple sources. 

Table 3. Selected ICD-10-CM drug resistance codes

Drug Code
Multi-drug Z16.24
Penicillins Z16.11
Cephalosporins Z16.19
Quinolones Z16.23
Vancomycin Z16.21
Aminoglycosides Z16.29
Antifungal Z16.32
Antimycobacterial, multiple drugs Z16.342
Antiparasitic Z16.31
Antiviral Z16.33

Source: ICD-10-CM.

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