Nosocomial infections

A nosocomial infection (from Latin nosocomium - hospital and Greek nosokomeo - to care for a patient; synonyms: nosocomial infections, hospital infections, health care associated infection) is any clinically recognizable infectious disease that develops in a patient as a result of his/her visit to a hospital for medical care or stay in it, as well as any infectious disease of a hospital employee that developed as a result of his/her work in this institution, regardless of the time of onset of symptoms (after or during a stay in the hospital) - WHO Regional Office for Europe, 1979. Infections are considered nosocomial if they develop at least 48 hours after admission to the clinic (excluding those cases when the patient is admitted to a medical institution during the incubation period of an infectious disease, the duration of which is more than 48 hours).

Nosocomial infections also include cases where a patient is re-admitted to hospital with an established infection that was a consequence of a previous hospitalization.

Nosocomial infections (NI) are a serious medical, social, economic and legal problem in intensive care units all over the world. Their frequency depends on the profile and architectural and technical features of the unit, as well as on the adequacy of the infection control program and averages 11%. The development of infectious complications in an ICU patient significantly increases mortality, increases the duration and cost of inpatient treatment.

The prevalence of nosocomial infections associated with the use of various invasive techniques is calculated using the formula:

Number of nosocomial infections over a given period x 1000 - total number of days of use of the invasive device

According to the National Nosocomial Infections Surveillance (NNIS) epidemiological surveillance of hospital-acquired infections in the USA (2002), the prevalence rate of nosocomial infections in “mixed” intensive care units of clinical hospitals, calculated using the above formula, is 5.6 for NIVL, 5.1 for urinary tract infections, and 5.2 for catheter-associated angiogenic infections per 1000 days of device use/procedure.

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Nosological structure of nosocomial infections in intensive care

• Nosocomial pneumonia, including that associated with mechanical ventilation.
• Nosocomial tracheobronchitis.
• Urinary tract infections.
• Angiogenic infections.
• Intra-abdominal infections.
• Surgical site infections.
• Soft tissue infections (cellulitis, post-injection abscesses, infected bedsores).
• Nosocomial sinusitis.
• Nosocomial meningitis.
• Sources of nosocomial infection in intensive care unit patients.
• Endogenous source (~4/5) - the patient's microflora, present before admission and acquired in hospital
  • skin, teeth, nasopharynx, paranasal sinuses, oropharynx, gastrointestinal tract, genitourinary system, alternative foci of infection.
• Exogenous source (~1/5)
  • medical personnel, other patients, medical equipment, instruments, care items, air, contaminated aerosols and gases, non-sterile catheters and syringes, water and food products.

Pathogens inhabiting exogenous and endogenous reservoirs are in dynamic interaction. An infection caused by a breakthrough of a pathogen from an endogenous source in one patient can lead to an outbreak of nosocomial infection in the department due to cross-infection. This phenomenon consists of the transmission of the pathogen from one patient to another through an intermediate reservoir, which is medical equipment, care items, hands and gloves of medical personnel. The literature contains indications of the role of mobile phones and phonendoscopes in the spread of hospital microflora.

Translocation of opportunistic bacteria from the gastrointestinal tract plays a major role in the pathogenesis of nosocomial infection. Under the influence of surgical stress, trauma, hemodynamic and metabolic disorders, and other pathological conditions, intestinal ischemia develops, leading to damage to enterocytes and disruption of its motor, secretory, and barrier functions. Retrograde colonization of the upper gastrointestinal tract by pathogenic microorganisms occurs, as well as translocation of bacteria and their toxins into the portal and systemic bloodstream.

Polysystemic bacteriological analysis in patients in the intensive care unit confirmed that the dynamics of contamination of the abdominal cavity, gastrointestinal tract, bloodstream, urinary tract, and lung tissue depend on the morphofunctional insufficiency of the intestine.

The development of a nosocomial infection in an intensive care unit patient is a consequence of an imbalance between the factors of microorganism aggression (adhesiveness, virulence, ability to form biofilms, the “quorum sensing” system, induction of cytokinogenesis, release of endo- and exotoxins) and the factors of the patient’s anti-infective defense (functional adequacy of mechanical and physiological barriers, innate and acquired immunity).

Microbiological structure of nosocomial infection in intensive care units

• Gram-positive bacteria
  • S aureus,
  • CoNS,
  • enterococci.
• Gram-negative bacteria
  • Enterobacteriaceae (E. coli, K. pneumoniae, Proteus spp, Enterobacter spp, Serratia spp),
  • non-fermenting bacteria (Pseudomonas spp, Acinetobacter spp, Xanthomonas maltophilia),
  • anaerobes (Bacteroides spp, Clostridium difficile).
• Mushrooms
  • Candida spp,
  • Aspergillus spp.
• Viruses
  • hepatitis B and C viruses,
  • HIV,
  • influenza virus,
  • respiratory syncytial virus,
  • herpes virus.
• Other microorganisms
  • Legionella spp,
  • M. tuberculosis,
  • Salmonella spp.

More than 90% of all nosocomial infections are of bacterial origin. Nosocomial infection pathogens are characterized by increased resistance to antimicrobial drugs. From 50 to 100% of hospital-acquired staphylococci strains are resistant to oxacillin and other ß-lactams, enterococci demonstrate high resistance to ampicillin, gentamicin and cephalosporins, in foreign literature there are reports of vancomycin-resistant strains, among representatives of the Enterobacteriaceae family there is a large proportion of extended-spectrum beta-lactamase producers, non-fermenting gram-negative pathogens have the greatest potential for developing resistance to antibiotics - most strains are insensitive to antipseudomonal penicillins, cephalosporins, aminoglycosides, fluoroquinolones, some - to carbapenems. The microbial structure and antibiotic resistance of pathogens causing nosocomial infections varies depending on the hospital profile, the microbial profile of a specific department and the hospital as a whole, so it is necessary to conduct local microbiological monitoring.

When treating nosocomial infections, a distinction should be made between empirical and etiotropic therapy.

The choice of drugs for empirical therapy is a complex task, since it depends on the antibiotic resistance of microorganisms in a particular medical institution, as well as on the presence of concomitant diseases, mono- or polymicrobial etiology of the infection and its localization. It has been established that an inadequate choice of the empirical antimicrobial therapy regimen increases mortality in patients with nosocomial infection by more than 4 times (RR - 4.8, 95% CI - 2.8-8.0, p <0.001). On the contrary, adequate initial antimicrobial therapy has a protective effect (RR - 0.27, 95% CI - 0.17-0.42, p <0.001). It is necessary to emphasize the undoubted importance of microbiological express analysis with Gram staining of clinical material obtained before the appointment or change of the antibacterial therapy regimen. This method allows one to quickly obtain information about the suspected pathogen and to plan antibacterial therapy in a differentiated manner, already at an early stage.

Based on the results of studying the spectrum of pathogens of the main nosocomial infections and their sensitivity to antimicrobial drugs, it is possible to propose schemes of empirical antibacterial therapy for hospital infectious complications in intensive care units.

Schemes of empirical antibacterial therapy for nosocomial infections in intensive care units

Localization	Gram staining result	Main pathogens	Drugs of choice
Nosocomial pneumonia	+	S. aureus	Vancomycin Linezolid
	-	A. baumannii K. pneumoniae P. aeruginosa	Carbapenems Cefepime + amikacin Cefolerazone/sulbactam ± amikacin
Intra-abdominal infections	+	Enterococcus spp. S. aureus	Vancomycin Linezolid
		A. baumann P. aeruginosa K. pneumoniae E. coli	Carbapenems Cefepime + amikacin Cefolerazone/sulbactam + amikacin
Wound infections	+	Enterococcus spp. S. aureus	Vancomycin Linezolid
	-	P. aeruginosa K. pneumoniae	Carbapenems ± aminoglycosides (amikacin) Cefepime + amikacin Cefolerazone/sulbactam
Angiogenic infections	+	S. aureus	Vancomycin Linezolid
Urinary tract infections	+	Enterococcus spp. S aureus	Vancomycin Linezolid
	-	K. pneumoniae P. aeruginosa	Fluoroquinolones** Carbapenems Cefepime Cefolerazone/sulbactam
	Not painted	Candida spp.	Fluconazole

• * If mixed aerobic-anaerobic flora is suspected, it is advisable to include drugs with antianaerobic activity in the initial antibacterial therapy regimens (which do not have their own antianaerobic activity).
• ** Levofloxacin, moxifloxacin, ofloxacin.

For targeted therapy of hospital infections with established etiology, the following antimicrobial therapy regimens have been developed

Etiotropic therapy of hospital infectious complications

A. baumannii	Imipenem	0.5 g 4 times a day
	Meropenem	0.5 g 4 times a day
	Cefoperazone/sulbactam	4 g 2 times a day
	Ampicillin/sulbactam	1.5 g 3-4 times a day
R. aeruginosa	Imipenem	1 g 3 times a day
	Meropenem	1 g 3 times a day
	Cefepime ± amikacin	2 g 3 times a day 15 mg/kg per day
	Ceftazidime + amikacin	2 g 3 times a day 15 mg/kg per day
K. pneumoniae	Imipenem	0.5 g 4 times a day
	Cefepime	2 g 2 times a day
	Cefoperazone/sulbactam	4 g 2 times a day
	Amikacin	15 mg/kg per day
E. coli, P. mirabilis	Ciprofloxacin	0.4-0.6 g 2 times a day
	Amikacin	15 mg/kg per day
	Imipenem	0.5 g 3-4 times a day
	Cefoperazone/sulbactam	4 g 2 times a day
Enterobacter spp.	Imipenem	0.5 g 3-4 times a day
	Ciprofloxacin	0.4-0.6 g 2 times a day
Candida spp.	Fluconazole	6-12 mg/kg per day
	Amphotericin B	0.6-1 mg/kg per day

Risk factors for the development of nosocomial infections in intensive care units

Severity of the underlying disease, multiple sclerosis, poor nutrition, old age, immunosuppression.

The use of invasive treatment and diagnostic methods (endotracheal intubation and artificial ventilation, creation of permanent vascular access, long-term drainage of the bladder, monitoring of intracranial pressure.

Overcrowded departments, lack of staff, presence of “live reservoirs” of infection.

Angiogenic infection

The following diseases fall into this category:

• infectious complications associated with long-term vascular catheterization and infusion therapy,
• infectious complications associated with the implantation of a foreign body into the cardiovascular system,
• nosocomial endocarditis,
• infected phlebothrombosis.

It has been proven that infection and sepsis accompany routine procedures performed by anesthesiologists and intensivists (catheterization of central and peripheral veins and arteries) much more often than implantation of long-term intravascular devices.

For timely diagnosis of catheter-associated infections, the skin in the catheter area should be examined and palpated daily (of course, observing the rules of asepsis)

Diagnostic clinical and laboratory criteria for angiogenic infectious complications:

• the presence of SIRS,
• localization of the source of infection in the vascular bed in the absence of extravascular foci,
• bacteremia established in at least one of the microbiological blood tests conducted dynamically.

If catheter-associated angiogenic infection is suspected, additional criteria are used

• Identity of blood culture and microflora isolated from the distal end of an infected catheter.
• Growth >15 CFU using the semiquantitative catheter colonization assay.
• The quantitative ratio of the contamination of blood samples obtained through a catheter and from a peripheral vein was >5. To diagnose bacteremia, two blood samples were taken from intact peripheral veins at an interval of 30 minutes.

A blood sample is not taken from the catheter, except in cases where there is a suspicion of a catheter-associated infection. Blood is taken before antimicrobial agents are prescribed. If antibacterial therapy is already being administered, blood is taken before the next administration (taking) of the drug.

The main mechanisms of development of catheter-associated angiogenic infections

• colonization of the outer surface of the catheter with subsequent migration from the space between the catheter and the skin to the inner (intravascular) end of the catheter,
• colonization of the connector with subsequent migration along the inner surface of the catheter.

The leading element in the pathogenesis of infection of catheters, implants and prostheses is considered to be the formation of bacterial biofilms. Among clinically significant bacteria, the ability to form biofilms has been established for representatives of the Enterobactenaceae family, Staphylococcus spp., Streptococcus spp., Enterococcus spp., Actinomyces spp., Pseudomonas spp. and Haemophilus spp.

Pathogens of angiogenic infection S. aureus, CoNS, Enterococcus spp, E. coli, K pneumoniae, fungi.

Currently, coagulase-negative staphylococci cause up to a quarter of all angiogenic infections, whereas in the past these microorganisms were considered only as contaminants. This is not only a microbiological phenomenon or a consequence of poor asepsis. This saprophyte was able to demonstrate its pathogenicity only in the conditions of the ever-worsening immunodepression characteristic of modern life and the growing environmental consequences of the widespread use of antibiotics.

[ 7 ], [ 8 ], [ 9 ], [ 10 ], [ 11 ], [ 12 ]

Nosocomial urinary tract infections

Sources and routes of urinary tract infection

• microflora of the hands of medical personnel and the periurethral zone of the patient - contamination during catheterization,
• proliferation of bacteria between the outer wall of the catheter and the mucous membrane of the urethra - "external infection"
• contamination of the drainage bag with subsequent reflux of contents - intraluminal infection,
• hematogenous infection.

Up to 80% of all hospital-acquired urinary tract infections are associated with the use of urinary catheters and instrumental interventions on the urinary tract. The most common causes of bacterial penetration into the bladder in patients with a urethral catheter

• failure to observe aseptic rules when installing a catheter,
• disconnection of the catheter and drainage tube,
• contamination during bladder lavage,
• colonization of the drainage bag and retrograde flow of contaminated urine into the bladder.

Diagnostic criteria for nosocomial urinary tract infection

• fever >38 °C, leukocytosis, proteinuria, cylindruria, renal dysfunction,
• leukocyturia or pyuria (>10 leukocytes in 1 mm ³ ),
• isolation of the pathogen during quantitative microbiological examination of urine in a titer of >10 ⁵ CFU/ml.

Urine is obtained by catheterization of the bladder with a sterile urethral catheter in compliance with aseptic rules and is immediately sent to the microbiology laboratory.

With this diagnostic approach, urinary tract infections are recorded in 3.7% of ICU patients.

Pathogens of hospital-acquired urinary tract infections: E. coli, Klebsiella spp., Proteus spp., Enterococcus spp., Enterobacter spp., Staphylococcus spp., Acinetobacter spp., Candida fungi.

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Antibacterial drugs for the treatment of hospital-acquired urinary tract infections

[ 20 ], [ 21 ], [ 22 ], [ 23 ], [ 24 ], [ 25 ]

Acute uncomplicated cystitis

• fluoroquinolones orally (levofloxacin, pefloxacin, ofloxacin, ciprofloxacin),
• fosfomycin, trometamol

[ 26 ], [ 27 ], [ 28 ], [ 29 ], [ 30 ], [ 31 ]

Pyelonephritis in intensive care unit patients

• ceftazidime,
• cefoperazone,
• cefepime,
• carbapenems,
• intravenous fluoroquinolones.

The duration of treatment is at least 14 days with mandatory bacteriological control.

Nosocomial surgical site infections

This group of infections, which account for 15-25% of all hospital-acquired infections, includes infections of surgical, burn and traumatic wounds. The frequency of their development depends on the type of surgical intervention: clean wounds - 1.5-6.9%, conditionally clean - 7.8-11.7%, contaminated - 12.9-17%, "dirty" - 10-40%.

The leading causative agent of nosocomial wound infection remains S. aureus, CoNS most often cause post-transplant infections, E. coli and other representatives of the Enterobacteriaceae family are the dominant pathogens in abdominal surgery and infections in obstetrics and gynecology.

Nosocomial intra-abdominal infections

The following infections are distinguished:

• postoperative secondary peritonitis,
• tertiary peritonitis,
• disorders of mesenteric circulation (ischemia/infarction),
• acalculous cholecystitis,
• infected pancreatic necrosis,
• gastrointestinal perforations (ulcers, tumors),
• antibiotic-associated pseudomembranous colitis.

In the microbiological structure of nosocomial intra-abdominal infectious complications, gram-negative microorganisms predominate (63.8%), of which Acinetobacter baumanu (12.8%), Pseudomonas aeruginos and E. coli (no 10.6%) are most often isolated. Gram-positive microflora is represented by various strains of Enterococcus spp. (19.2%), Staphylococcus aureus - 10.6% (80% of isolated golden staphylococci are resistant to oxacillin). The etiological structure of nosocomial intra-abdominal infections proves their typical hospital nature. Hospital-acquired pathogens predominate, while in community-acquired intra-abdominal infections, the most significant etiological role is played by Escherichia, Proteus and Bacteroides.

Drugs for the treatment of pseudomembranous colitis caused by C. difficile

• metronidazole (orally),
• vancomycin (oral)

Prevention of hospital-acquired infections

High-quality, evidence-based nosocomial infection prevention programs can reduce their incidence, length of hospital stay, and cost of treatment. The proportion of nosocomial infections that can be prevented by infection control measures is 20 to 40%. Infection control measures should be given priority funding.

The following principles must be observed:

• staff training,
• epidemiological control,
• interruption of infection transmission mechanisms,
• elimination of factors suppressing the patient’s anti-infective defenses (exogenous and endogenous).

Prevention of nosocomial infections

Risk factors for hospital-acquired infection	Preventive measures
Overcrowding of departments, concentration of patients with infections in intensive care units, lack of space and personnel	Isolation of patients with NI, creation of separate nursing stations Strict adherence to the rules of antiseptic hand hygiene Use of sterile gloves Use of highly effective antiseptics Preferable use of disposable consumables High-level sterilization and disinfection
Selection of highly resistant strains of pathogens in conditions of widespread use of antimicrobial drugs (selective pressure of antibiotics)	Establishment of an infection control service in the hospital (clinicians + pharmacies + financially responsible persons) Development of in-hospital protocols and forms Careful local microbiological monitoring Ensuring adequate initial therapy for severe infections (de-escalation empirical therapy) Adequate dosing of antibiotics, if necessary - monitoring of plasma concentrations Compliance with the timing of antibacterial therapy Exclusion of ineffective drugs Rotation of antibiotics
SKN, translocation of microbes and their toxins in critically ill patients	Selective decontamination of the gastrointestinal tract in patients with a high risk of developing NI Indications: widespread peritonitis, severe sepsis and multiple myelopathy (of any etiology), pancreatic necrosis, liver transplant
High probability of fungal microflora breakthrough from endogenous ecotopes in patients in critical conditions	Prevention of systemic candidiasis Indications pancreatic necrosis and surgical interventions on the pancreas, colon perforation, gastrointestinal anastomotic failure, postsplenectomy syndrome, prolonged (>7 days) mechanical ventilation, prolonged parenteral nutrition, PON, immunosuppressive states (in particular, prolonged glucocorticoid therapy)
Tracheal intubation and artificial ventilation	Continuous aspiration from the subglottic space Semi-sitting position in bed Prevention of gastric overdistension Limitation of stress ulcer prophylaxis with antacids Treatment of the oral cavity with chlorhexidine Use of techniques to prevent spontaneous extubation, adherence to the rules for performing reintubation Limitation of the use of muscle relaxants and CNS depressants Limitation of indications for nasotracheal intubation (risk of sinusitis) "Early" tracheostomy performed under sterile conditions Use of closed aspiration systems Timely removal of any condensate in the circuit Use of bacterial filters
	Vascular catheterization strictly according to indications and compliance with catheterization terms Compliance with contact precautions during catheter installation (sterile gloves, gown, mask, covering with sterile linen) Ensuring maximum sterility at the catheterization site Use of modern antiseptics with proven effectiveness for treating the hands of medical personnel, patient skin, injection ports Careful care of the catheter insertion site (adequate skin treatment, prevention of moisture accumulation, sterile dressing - gauze or transparent semipermeable sticker, daily palpation of the catheterization site or observation through a transparent sticker) Immediate change of infusion systems after transfusion of blood components and fat emulsions
	Quality control of infusion media If there are no signs of infection, do not routinely replace the central venous catheter If infection develops, do not replace the catheter over the guidewire (change the catheterization site) Subcutaneous tunneling of the catheter in patients from the high group Replace catheters installed in an emergency without full compliance with the rules of asepsis and antisepsis immediately after stabilization of the patient's hemodynamics, but no later than 48 hours
Urinary catheters	Training of personnel in catheterization techniques Catheterization of the bladder only for strict indications Strict adherence to the rules of asepsis and antisepsis during catheterization Intermittent catheterization Use of closed drainage systems Ensuring free flow of urine Timely replacement of the catheter Refusal of routine rinsing of the drainage system and bladder
	Before applying an antiseptic, the surgical site should be cleaned with a detergent. Antiseptics with proven efficacy should be used to prepare the skin of the surgical site. Glucose levels should be adequately controlled in all patients with diabetes, especially avoiding hyperglycemia in the perioperative period. Perioperative antibacterial prophylaxis should be prescribed only when indicated, taking into account the risk of developing infectious complications, and the drug for its use should be selected based on its activity against the most common pathogens of surgical site infections in specific procedures and on published recommendations. Surgical aspects of surgical site infection prevention effective hemostasis, prevention of hypothermia,
Surgical interventions	Operating room preparation Equipping with positive pressure ventilation systems of sufficient capacity Air filtration Maintaining an optimal microclimate (temperature 18-24 C, humidity 50-55%) Closed doors and windows Reasonable limitation of the number of personnel Sticky mats at the entrance to the operating room and ultraviolet irradiation should not be used to prevent infections in the surgical area Preparation of the operating room and anesthesia team A surgical suit, mask and headgear that completely covers the hair are required Compliance with hand hygiene rules, refraining from using brushes and sponges before each operation Use of high-quality sterile gloves Use of two pairs of gloves for a number of interventions (orthopedic operations, sternotomy) Suspend personnel with signs of general infectious diseases and infectious skin lesions from work Patient preparation Whenever possible, it is necessary to identify and treat all infections other than the area of intervention, localization Do not remove hair from the surgical field unless it can interfere with the operation If necessary, remove hair immediately before For removal hair removal should be done with clippers and depilatories, not razors
Intravascular/intracardiac catheters and implants	Training of personnel in the rules of working with catheters, devices and caring for them, periodic assessment of knowledge of the rules of asepsis and antisepsis, catheterization skills and catheter care
	careful handling of tissues, removal of non-viable tissues, adequate use of drains and suture material , elimination of small cavities, proper care of the surgical wound

Organizational and sanitary-hygienic measures necessary for the prevention of various types of nosocomial infections:

• modern architectural and technical solutions,
• epidemiological surveillance of (or monitoring) nosocomial infections,
• isolation of patients with purulent-septic complications,
• implementation of the principle of a minimum number of patients per nurse,
• reduction of the preoperative period,
• creation of federal and local protocols and forms,
• the use of highly effective antiseptics (or antiseptics with proven effectiveness),
• strict adherence to hand hygiene rules by medical personnel,
• carrying out high-quality sterilization and disinfection,
• training of personnel in the rules of working with invasive devices and instruments, periodic assessment of knowledge of the rules of asepsis and antisepsis, catheterization skills and catheter care,
• removal of invasive devices immediately after the clinical indications for their use disappear,
• use of invasive devices with antimicrobial and biofilm-inhibiting coatings.