Nosocomial infections

Nosocomial infections, also known as hospital-acquired infections, are newly acquired infections that are contracted within a hospital environment. Transmission usually occurs via healthcare workers, patients, hospital equipment, or interventional procedures. The most common sites of infection are the bloodstream, lungs, urinary tract, and surgical wounds. Though any bacteria may cause a nosocomial infection, there is an increasing incidence of multidrug-resistant pathogens (MDR) causing hospital-acquired infections. This rise can be explained by indiscriminate use of antibiotics and lacking hygiene measures, especially among medical staff. Commonly seen multidrug-resistant pathogens include methicillin-resistant Staphylococcus aureus (MRSA), extended-spectrum beta-lactamase-producing bacteria (ESBL), and vancomycin-resistant enterococci (VRE). The choice of antibiotic for treating infections with these pathogens is based on the individual resistance profile and often requires additional strict isolation methods for the patient.

• Nosocomial infections are defined as infections acquired after hospitalization and occur within 48 hours of hospital admission, 3 days of discharge or 30 days of an operation. ^[1]
• At admission, these infections are not present or incubating.

Common causative pathogens ^[2]

Risk factors ^[1][2][4]

• Age > 70 years
• Lengthy hospital stays → ↑ risk of infection
  • Medical staff (e.g., insufficient disinfection of hands, clothing)
  • Contact surfaces (e.g., equipment, furniture)
  • Indoor air (e.g., via contaminated by droplets from infected patients, staff, procedures like bronchoscopy)
• Iatrogenic: caused by treatment or a diagnostic procedure
  • Foreign bodies (e.g., catheters, intravenous catheters, endotracheal tubes) and invasive instruments
  • Conditions which require a high amount of interventional procedures (e.g., shock, major trauma, acute renal failure, coma)
  • Mechanical ventilation
• Prior antibiotic use
• Metabolic diseases (especially diabetes mellitus)
• Immunosuppression

Methicillin-resistant Staphylococcus aureus (MRSA)

• Resistance
  • Form a modified penicillin-binding protein (PBP) that inhibits binding of beta-lactam antibiotics, thereby decreasing their bactericidal effect.
  • Modified PBPs are encoded by the mecA gene on the staphylococcal chromosome. ^[5]
• Epidemiology: asymptomatic colonization of the nasal mucosa estimated at 0.5–5% of the population
• Diseases: nosocomial and community-acquired infections
• Measures
  • Hygiene measures
    • Hand disinfection
    • Protective clothing (gown, mask)
    • Disinfection of patient rooms
  • Patient isolation (if necessary, cohort isolation)
  • MRSA eradication in asymptomatic carriers
    • Mupirocin nasal ointment
    • Antiseptic solution for skin/hair contamination (e.g., chlorhexidine)

The resistance mechanism of MRSA relies on modified PBPs, not the formation of beta-lactamase. Every case of MRSA (symptomatic or asymptomatic) requires treatment.

Extended-spectrum beta-lactamase-producing bacteria (ESBL)

• Resistance: Bacteria produce beta-lactamases that have a broad spectrum and cleave penicillins, cephalosporins, and, in isolated cases, carbapenems.
• Pathogens: : particularly gram-negative bacteria; (e.g., Enterobacteriaceae such as Klebsiella, Escherichia coli)
• Diseases
  • Nosocomial urinary tract infections
  • Healthcare-associated pneumonia
• Measures: isolation in separate rooms required

Vancomycin-resistant enterococci (VRE)

• Definition: bacterial strains of the genus Enterococcus that are resistant to vancomycin (e.g., E. faecalis, E. faecium)
• Resistance: acquisition of van genes (e.g., through transposition of plasmid-encoded genes) → alteration of peptidoglycan synthesis pathway (e.g., due to change from the d-alanine-d-alanine amino acid sequence to d-alanine-d-lactate) → inhibition of vancomycin binding to peptidoglycan

Multidrug-resistant gram-negative bacteria (MDRGNB) ^[6]

• Definition: gram-negative pathogens that are resistant to at least three of the four main antibiotic classes.
• Measures
  • Suspected cases: no isolation
  • Confirmed cases
    • Basic hygiene measures in normal areas sufficient
    • Isolation in risk areas (e.g., intensive care, neonatology, hematology-oncology)

Pseudomonas aeruginosa

• Resistance: high natural resistance to antibiotics
• Diseases
  • Pneumonia
  • Severely infected wounds
  • Urinary tract infections
  • Otitis externa (swimmer's ear)
  • Keratitis

• Definition
  • Catheter-related bloodstream infection (CRBSI) is a bloodstream infection attributed to an intravascular catheter.
• Risk factors
  • Immunosuppression
  • Bone marrow transplant
  • Burn
  • Catheter type: central venous catheters
  • Sites of insertion: femoral and inguinal catheter insertion sites have high risk for infection while the subclavian site carry less risk
• Etiology: the most common pathogens are:
  • Coagulase-negative staphylococci
  • S. aureus
  • Enterococci
  • Candida species
• Clinical features
  • Fever
  • Hemodynamic instability
  • Swelling, pain, redness, and purulence at catheter insertion sites
  • Altered mental status
• Diagnosis
  • Approach: Catheter-related blood stream infection should be suspected in patients presenting with septic features 48 hours after insertion of the catheter.
  • Blood culture: samples should be collected prior to initiation of antibiotics
    • Collect two blood samples from a peripheral venous site (ideal)
      OR
    • Collect one blood sample from a peripheral venous site and culture the catheter tip
      OR
    • Collect one blood sample from a peripheral venous site and another sample from a catheter hub
• Definitive diagnosis if:
  • The same organism grows from the catheter tip (> 15 colony-forming units [CFUs]/plate using semiquantitative culture or 10²CFU using quantitative culture) and percutaneous blood sample.
  • The same organism grows from the percutaneous blood sample and catheter hub blood sample, with a 3-fold colony count in the latter.
  • The same organism grows from the percutaneous blood sample and catheter hub blood sample, with the microbe being detected 2 hours earlier in the latter.
• Treatment
  • Short-term catheters should be removed from patients with catheter related blood stream infection that is caused by the following pathogens:
    • Gram-negative bacilli
    • S. aureus
    • Enterococci
    • Fungi
    • Mycobacteria
  • Long-term catheters should be removed in the following cases:
    • Severe sepsis
    • Suppurative thrombophlebitis
    • Endocarditis
    • Persistent bloodstream infection despite > 72 hours of antimicrobial therapy
    • Infections caused by the following pathogens:
      • S. aureus
      • P. aeruginosa
      • Fungi
      • Mycobacteria
• Start empiric treatment
  • Drug of choice depends on:
    • Severity of illness
    • Suspected pathogens
    • Presence of other comorbid conditions
  • Gram-positive pathogens
    • Vancomycin is recommended in an institution with high rate of MRSA infection.
    • Use alternate agents such as daptomycin if the MRSA isolates have vancomycin minimum inhibitory concentration (MIC) values > 2 μg/mL.
  • Gram-negative bacilli
    • Choose antibiotics based on the local antimicrobial susceptibility data and the severity of the illness.
    • Pseudomonas aeruginosa should be covered with agents such as imipenem, ceftazidime, cefepime, OR piperacillin-tazobactam in:
      • Neutropenic patients
      • Burn patients
      • Hemodynamically unstable patients with sepsis
      • Patients known to be colonized with such pathogens
  • Candida species
    • Individuals at risk should be treated with echinocandin.
    • This includes:
      • Colonization of Candida species at multiple sites
      • Femoral catheterization
      • Hematologic malignancy
      • Prolonged use of broad-spectrum antibiotics
      • Total parenteral nutrition
• Prevention: See ”Prevention of intravascular catheter-related infections.”

References: ^[9][10][11]

1. Choo EJ, Chambers HF. Treatment of Methicillin-Resistant Staphylococcus aureus Bacteremia. Infection & Chemotherapy. 2016; 48 (4): p.267. doi: 10.3947/ic.2016.48.4.267 . | Open in Read by QxMD
2. Multi-Drug Resistant Gram Negative Bacilli (MDRGNB). http://www.hopkinsmedicine.org/heic/infection_surveillance/mdrgnb.html. Updated: February 12, 2017. Accessed: February 12, 2017.
3. O’Grady NP, Alexander M, Burns LA, et al. Guidelines for the Prevention of Intravascular Catheter-related Infections. Clinical Infectious Diseases. 2011; 52 (9): p.e162-e193. doi: 10.1093/cid/cir257 . | Open in Read by QxMD
4. Shah H, Bosch W, Thompson KM, Hellinger WC. Intravascular Catheter-Related Bloodstream Infection. The Neurohospitalist. 2013; 3 (3): p.144-151. doi: 10.1177/1941874413476043 . | Open in Read by QxMD
5. Rupp ME, Karnatak R. Intravascular Catheter–Related Bloodstream Infections. Infect Dis Clin North Am. 2018; 32 (4): p.765-787. doi: 10.1016/j.idc.2018.06.002 . | Open in Read by QxMD
6. Wielders CLC, Fluit AC, Brisse S, Verhoef J, Schmitz FJ. mecA Gene Is Widely Disseminated in Staphylococcus aureus Population. J Clin Microbiol. 2002; 40 (11): p.3970-3975. doi: 10.1128/jcm.40.11.3970-3975.2002 . | Open in Read by QxMD
7. New Guidelines Available on the Prevention and Control of Multi-Drug-Resistant Gram-Negative Bacteria in Hospitals. https://www.elsevier.com/about/press-releases/research-and-journals/new-guidelines-available-on-the-prevention-and-control-of-multi-drug-resistant-gram-negative-bacteria-in-hospitals. Updated: November 18, 2015. Accessed: February 12, 2017.
8. National and State Healthcare Associated Infections Progress Report 2016. https://www.cdc.gov/HAI/pdfs/progress-report/hai-progress-report.pdf. Updated: March 3, 2016. Accessed: February 12, 2017.
9. Chiche L, Forel J-M, Papazian L. The role of viruses in nosocomial pneumonia. Curr Opin Infect Dis. 2011; 24 (2): p.152-156. doi: 10.1097/qco.0b013e328343b6e4 . | Open in Read by QxMD
10. WHO Guidelines on Hand Hygiene in Health Care: a Summary. http://www.who.int/gpsc/5may/tools/who_guidelines-handhygiene_summary.pdf. Updated: January 1, 2009. Accessed: February 12, 2017.
11. Inweregbu K, Dave J, Pittard A. Nosocomial infections. Continuing Education in Anaesthesia Critical Care & Pain. 2005; 5 (1): p.14-17. doi: 10.1093/bjaceaccp/mki006 . | Open in Read by QxMD