Multidrug-Resistant Organisms & Infection Control
Which precautions, which hand hygiene, which drug for which resistance
Standard precautions and hand hygiene
Standard precautions apply to every patient, whatever the diagnosis: hand hygiene before and after patient contact, gloves for anticipated contact with blood, body fluids, mucous membranes or broken skin, gown and eye protection when splashes are likely, safe injection practice, and respiratory hygiene (masking and cough etiquette) for anyone with respiratory symptoms. Transmission-based precautions are added on top, not substituted.
Hand hygiene is the single most effective measure for preventing health care–associated infection. Alcohol-based hand rub is the default: it is faster, kills most bacteria and enveloped viruses more effectively than soap, and improves adherence. Soap and water are required when hands are visibly soiled and after caring for patients with C. difficile, whose spores resist alcohol, or norovirus, a nonenveloped virus that is relatively alcohol-resistant. Gloves never replace hand hygiene; hands are cleaned again after gloves come off.
Transmission-based precautions
| Type | What staff do | Room | Key organisms |
|---|---|---|---|
| Contact | Gown and gloves on entry; dedicated equipment | Single room or cohort | MRSA, VRE, ESBL and carbapenemase producers, C. difficile, norovirus, scabies, lice, RSV in young children |
| Droplet | Surgical mask on entry | Single room | Influenza, pertussis, N. meningitidis, invasive Hib, mumps, rubella, Mycoplasma |
| Airborne | Fit-tested N95 respirator or PAPR | Negative-pressure airborne-infection isolation room, door closed | TB, measles, varicella, disseminated zoster |
Contact precautions. For C. difficile, rooms are cleaned with a sporicidal (bleach-based) agent, and precautions are commonly continued for at least 48 hours after diarrhea resolves. Scabies precautions continue until 24 hours after effective treatment.
Droplet precautions. Large respiratory droplets travel only about 1–2 meters and fall quickly, so a surgical mask is adequate. Precautions stop after 24 hours of effective antibiotics for N. meningitidis and invasive H. influenzae type b, after 5 days of effective therapy for pertussis, and 5 days after the onset of parotid swelling for mumps.
Airborne precautions. Droplet nuclei remain suspended and travel on air currents, so the patient needs a negative-pressure room and staff need fit-tested N95 respirators or powered air-purifying respirators. The patient wears a surgical mask during transport. Only staff with documented immunity should care for patients with measles or varicella, and exposed nonimmune staff are kept off work through the incubation period. Suspected pulmonary TB stays in isolation until an alternative diagnosis is established or, on effective therapy with clinical improvement, three sputum AFB smears collected at least 8 hours apart (one in the early morning) are negative. Measles isolation lasts through 4 days after rash onset in immunocompetent patients, and varicella isolation lasts until all lesions have crusted.
Preventing device-associated infections
Device days drive infection. The most effective prevention for central line–associated bloodstream infection (CLABSI) and catheter-associated urinary tract infection (CAUTI) is to avoid unnecessary devices and to remove them as soon as they are no longer needed, with a daily review of every line and catheter.
- Central lines: hand hygiene, maximal sterile barrier precautions, chlorhexidine-alcohol skin antisepsis, avoidance of the femoral site in adults, and prompt removal.
- Urinary catheters: insert only for clear indications, maintain a closed drainage system, use nurse-driven removal protocols, and do not screen for or treat asymptomatic bacteriuria.
Resistant gram-positive organisms
MRSA. Methicillin resistance comes from mecA, which encodes PBP2a, a penicillin-binding protein with low affinity for β-lactams. Serious infections are treated with IV vancomycin (AUC-guided), daptomycin or linezolid. Daptomycin is ideal for bacteremia and endocarditis but is inactivated by surfactant, so it is never used for pneumonia; linezolid and vancomycin are the pneumonia options. Ceftaroline is a cephalosporin that binds PBP2a. For outpatient purulent skin infection, incision and drainage is the key step, adding TMP-SMX, doxycycline or clindamycin for extensive disease or systemic signs. Clindamycin needs a D-test, because erythromycin-resistant strains can carry inducible clindamycin resistance.
Decolonization. Recurrent MRSA skin infections despite good hygiene, and S. aureus carriage before cardiac or orthopedic surgery, justify intranasal mupirocin twice daily for 5 days plus chlorhexidine body washes. ICUs that bathe all patients daily with chlorhexidine reduce bloodstream infections. A negative MRSA nasal PCR has a very high negative predictive value for MRSA pneumonia and supports stopping empiric vancomycin.
Rifampin should never be used alone against S. aureus, because resistance emerges rapidly.
VRE. Enterococci become vancomycin-resistant by acquiring vanA or vanB genes, which replace the terminal D-Ala-D-Ala of peptidoglycan precursors with D-Ala-D-Lac. Most VRE are E. faecium. Linezolid or high-dose daptomycin is used; ampicillin remains effective when the isolate is ampicillin-susceptible, as many E. faecalis strains are. Enterococci are intrinsically resistant to cephalosporins.
Resistant gram-negatives and Candida auris
| Problem | Typical organisms | What it destroys | Preferred therapy |
|---|---|---|---|
| ESBL | E. coli, Klebsiella | Penicillins, cephalosporins including cefepime, aztreonam | Carbapenem for serious infection; nitrofurantoin or TMP-SMX for cystitis |
| Inducible AmpC | Enterobacter cloacae, K. aerogenes, Citrobacter freundii | Third-generation cephalosporins once derepressed | Cefepime; carbapenem if cefepime MIC is high |
| KPC carbapenemase (CRE) | Klebsiella, other Enterobacterales | Nearly all β-lactams, including carbapenems | Ceftazidime-avibactam, meropenem-vaborbactam, imipenem-relebactam |
| Metallo-β-lactamase (NDM) | Enterobacterales | Carbapenems and the newer inhibitor combinations | Ceftazidime-avibactam plus aztreonam, or cefiderocol |
| Difficult-to-treat Pseudomonas | P. aeruginosa | All first-line antipseudomonal agents | Ceftolozane-tazobactam, ceftazidime-avibactam or imipenem-relebactam; cefiderocol alternative |
ESBL producers. For bacteremia and other serious infections a carbapenem is preferred: meropenem, or once-daily ertapenem when Pseudomonas is not a concern. In the MERINO trial, piperacillin-tazobactam was associated with higher mortality than meropenem for ceftriaxone-resistant E. coli and Klebsiella bloodstream infection, even when the isolate tested susceptible. Once the patient improves, oral step-down to TMP-SMX or a fluoroquinolone is reasonable if the isolate is susceptible.
AmpC producers. Organisms with chromosomal, inducible AmpC may test ceftriaxone-susceptible at first, but therapy can select stably derepressed mutants that hydrolyze third-generation cephalosporins and cause relapse. Cefepime is a poor AmpC substrate and is preferred for invasive infection.
Carbapenem-resistant Enterobacterales. In the US, KPC is the dominant carbapenemase. Metallo-β-lactamases such as NDM are not inhibited by avibactam, vaborbactam or relebactam; aztreonam is spared by them, which is why it is paired with ceftazidime-avibactam. CRE require strict contact precautions, screening of exposed patients when recommended, and reporting to public health.
Candida auris. This emerging yeast spreads within hospitals and long-term care facilities (especially among ventilated patients and those with devices), colonizes skin for long periods and persists on surfaces. Most isolates are fluconazole-resistant, some resist amphotericin B and a few resist echinocandins, and conventional identification methods can misidentify it. Invasive infection is treated with an echinocandin. Patients are placed on contact precautions in acute care (enhanced barrier precautions for colonized nursing home residents), rooms are cleaned with disinfectants proven effective against C. auris (quaternary ammonium products are not), and cases are reported to public health.