Nosocomial infections

Nosocomial infection (from lat nosocomium - hospital and Greek nosokomeo - to care for the patient, synonyms: hospital infections, hospital infections, health care associated infection) is any clinically recognizable infectious disease that develops in the patient as a result of his treatment in the hospital for medical treatment or stay in it, as well as any infectious disease of a hospital employee that has developed as a result of his work in this institution, regardless of the time of onset of symptoms (after or while in hospital) WHO Regional Office, WHO, 1979. Infections considered nosocomial if they develop at least 48 hours after admission to hospital (except in cases when the patient goes to the hospital in the incubation period of an infectious disease, the duration of which more than 48 hours).

Nosocomial infections include cases when a patient re-enters a hospital with an established infection that was a consequence of a previous hospitalization.

Nosocomial infections are a serious medical, social, economic and legal problem in intensive care units around the world. The frequency of their development depends on the profile and architectural and technical features of the department, as well as on the adequacy of the infection control program and averages 11%. The development of infectious complications in the patient's ICU significantly increases lethality, increases the duration and cost of inpatient treatment.

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

The number of cases of nosocomial infections for a certain period x 1000 - the total number of days of use of the invasive device

According to the National Nosocomial Infection Surveillance (NNIS) of epidemiological surveillance of nosocomial infections in the United States (2002), the prevalence of nosocomial infections in "mixed" ICU clinical hospitals, calculated according to the above formula, is 5.6 for NPIVL, 5 for urinary tract infections , 1 and for catheter-associated angiogenic infections - 5.2 per 1000 days of device / procedure application.

[1], [2], [3], [4], [5], [6],

Nosological structure of nosocomial infections in intensive care

• Nosocomial pneumonia, including those associated with ventilation.
• Nosocomial tracheobronchitis.
• Urinary tract infections.
• Angiogenic infections.
• Intraabdominal infections.
• Infections of the field of surgical intervention.
• Infections of soft tissues (cellulite, postinjection abscesses, infected bedsores).
• Nosocomial sinusitis.
• Nosocomial meningitis.
• Sources of nosocomial infection of patients with ICU.
• Endogenous source (~ 4/5) - the patient's microflora, which was available before admission and was acquired in a hospital
  • skin, teeth, nasopharynx, paranasal sinuses, oropharyngeal, gastrointestinal tract, genitourinary system, alternative foci of infection.
• Exogenous source (~ 1/5)
  • medical staff, other patients, medical equipment, instruments, care items, air, contaminated aerosols and gases, non-sterile catheters and syringes, water and food.

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

The great importance in the pathogenesis of nosocomial infection is the translocation of opportunistic pathogens from the digestive tract. Under the influence of surgical stress, trauma, hemodynamic disorders, metabolism and in 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 with pathogenic microorganisms occurs, as well as the translocation of bacteria and their toxins into the portal and systemic bloodstream.

Polysystemic bacteriological analysis in patients with ICU confirmed that the dynamics of contamination of the abdominal cavity, gastrointestinal tract, blood channel, urinary tract, as well as lung tissue depends on the morphofunctional insufficiency of the intestine.

The development of nosocomial infection in the patient of the ICU is a consequence of an imbalance between the factors of the aggression of microorganisms (adhesiveness, virulence, the ability to form biofilms, the "quorum sensing" system, induction of cytokineogenesis, release of endo- and exotoxins) and the factors of the patient's anti-infection protection (functional fullness of mechanical and physiological barriers, congenital and acquired immunity).

Microbiological structure of nosocomial infection in the ICU

• 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. The causative agents of nosocomial infection are characterized by increased resistance to antimicrobial drugs. From 50 to 100% of nosocomial strains of staphylococcus are resistant to oxacillin and other ß-lactams, enterococci demonstrate high resistance to ampicillin, gentamicin and cephalosporins, in the foreign literature there are reports of vancomycin-resistant strains among representatives of the Enterobacteriaceae family a large proportion of producers of beta-lactamases of the extended spectrum, non-fermenting gram-negative pathogens possess the largest it has the potential to form resistance to antibiotics - most strains are insensitive to anti-synergic penicillins, cephalosporins, aminoglycosides, fluoroquinolones, some to carbapenems. The microbial structure and antibiotic resistance of pathogens of nosocomial infection varies depending on the profile of the hospital, the microbial profile of a particular department and the hospital as a whole, so it is necessary to conduct local microbiological monitoring.

In the treatment of nosocomial infections, empirical and etiotropic therapy should be distinguished.

The choice of drugs for empirical therapy is a complex task, as 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 was found that an inadequate choice of the regime of empirical antimicrobial therapy increases the lethality in patients with nosocomial infection by more than 4 times (RR - 4.8, 95% CI - 2.8-8.0, p <0.001). In contrast, 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 the Gram staining of the clinical material obtained before the appointment or change of antibiotic therapy. This method allows you to quickly obtain information about the proposed pathogen and differentially, at an early stage, to plan antibiotic therapy.

Based on the results of the study of the spectrum of pathogens of the major nosocomial infections and their sensitivity to antimicrobial agents, it is possible to propose schemes of empirical antibacterial therapy of hospital infectious complications in the ICU.

Schemes of empirical antibiotic therapy of nosocomial infections in intensive care units

Localization	Result of coloring on Gramm	Major pathogens	Drugs of choice
Nosocomial pneumonia	+	S. Aureus	Vancomycin Linezolid
	-	A. Baumannii C. Pneumoniae P. Aeruginosa	Carbapenems Cefepime + amikacin Cefolerazone / sulbactam ± amikacin
Intra-abdominal infections	+	Enterococcus spp. S. Aureus	Vancomycin Linezolid
		A. Baumannn P. Aeruginosa C. 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
	-	C. Pneumoniae P. Aeruginosa	Fluoroquinolones ** Carbapenems Cefepime Cefolerazone / sulbactam
	Not colored	Candida spp.	Fluconazole

• * If suspicion of a mixed aerobic-anaerobic flora in the start-up antibiotic therapy schemes (which do not have their own anti-anaerobic activity), it is advisable to include drugs that have anti-anaerobic activity.
• ** Levofloxacin, moxifloxacin, ofloxacin.

For the purposeful therapy of hospital infections with established etiology, the following regimens of antimicrobial therapy 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
C. Pneumoniae	Imipenem	0 5 g 4 times a day
	Cefepim	2 g 2 times a day
	Cefoperazone / sulbactam	4 g 2 times a day
	Amikacin	15 mg / kg per day
E. Coli, R. 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

The severity of the underlying disease, PON, undernutrition, advanced age, immunosuppression.

The use of invasive medical and diagnostic techniques (endotracheal intubation and ventilation, the creation of permanent vascular access, prolonged drainage of the bladder, monitoring of ICP.

Congestion departments, lack of staff, the presence of "living reservoirs" of infection.

Angiogenic infection

This category includes the following diseases:

• infectious complications associated with prolonged vessel catheterization and infusion therapy,
• infectious complications associated with the implantation of a foreign body in the cardiovascular system,
• nosocomial endocarditis,
• infected phlebotrombosis.

It is proved that infection and sepsis are much more often accompanied by daily manipulations of anesthesiologists and intensivists (catheterization of central and peripheral veins and arteries) than the implantation of long-acting intravascular devices.

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

Diagnostic clinical and laboratory criteria of angiogenic infectious complications:

• the existence of SSRM,
• localization of the source of infection in the vascular bed in the absence of extravascular foci,
• bacteremia, established at least in one of the microbiological blood tests conducted in the dynamics.

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

• Identity of the hemoculture and microflora isolated from the distal end of the infected catheter.
• Growth> 15 cfu with a semi-quantitative method for assessing catheter colonization.
• The quantitative ratio of the dissemination of blood samples obtained through a catheter and from a peripheral vein,> 5 For the diagnosis of bacteremia, two blood samples were taken from intact peripheral veins at an interval of 30 minutes.

Obtaining a blood sample from the catheter does not produce, except when there is a suspicion of a catheter-associated infection. Blood sampling is performed prior to the appointment of antimicrobial agents. If antibacterial therapy is already performed, the blood is taken before the next administration (reception) 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 internal (intravascular) end of the catheter,
• colonization of the connector followed by migration along the internal surface of the catheter.

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

Pathogens of angiogenic infection of 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 manifest its pathogenicity only in conditions of all the aggravated, characteristic for modern life immunodepression and the growing environmental consequences of widespread use of antibiotics.

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

Hospital-acquired infections of the urinary tract

Sources and routes of infection of the urinary tract

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

Up to 80% of all nosocomial infections of the urinary tract are associated with the use of urinary catheters and instrumental interventions on the urinary tract. The most frequent causes of bacteria entering the bladder in patients with a urethral catheter

• non-compliance with asepsis rules when installing a catheter,
• disconnection of the catheter and drainage tube,
• contamination during washing of the bladder,
• colonization of the drainage bag and retrograde inflow of contaminated urine into the bladder.

Diagnostic criteria for nosocomial infection

• fever> 38 ° C, leukocytosis, proteinuria, cylindruria, impaired renal function,
• leukocyturia or pyuria (> 10 leukocytes per 1 mm ³ ),
• excretory excretion in quantitative microbiological examination of urine in a titer> 10 ⁵ cfu / ml.

Urine is obtained with the help of catheterization of the bladder by a sterile urethral catheter with the observance of aseptic rules and immediately sent to a microbiological laboratory.

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

Pathogens of hospital-acquired uroinfection E. Coli, Klebsiella spp., Proteus spp., Enterococcus spp., Enterobacter spp., Staphylococcus spp., Acinetobacter spp., Fungi of the genus Candida.

[13], [14], [15], [16], [17], [18], [19]

Antibacterial drugs for the treatment of nosocomial infections of the urinary tract

[20], [21], [22], [23], [24], [25], [26],

Acute uncomplicated cystitis

• fluoroquinolones inwards (levofloxacin, pefloxacin, ofloxacin, ciprofloxacin),
• phosphomycin, trometamol

Pyelonephritis in patients with ICU

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

Duration of treatment - not less than 14 days with obligatory bacteriological control.

Nosocomial infections in the area of surgical intervention

To this group of infections, which account for 15-25% of all nosocomial infections, include infections of surgical, burn and traumatic wounds. The frequency of their development depends on the type of surgery for clean wounds - 1.5-6.9%, conditionally clean - 7 , 8-11.7%, contaminated - 12.9-17%, "dirty" - 10-40%.

The leading causative agent of wound nosocomial 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

Allocate the following infections:

• postoperative secondary peritonitis,
• tertiary peritonitis,
• disturbance of mesenteric circulation (ischemia / infarction),
• acalculous cholecystitis,
• infected pancreatic necrosis,
• Perforation of the gastrointestinal tract (ulcers, tumors),
• pseudomembranous colitis associated with the use of antibiotics.

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 the isolated Staphylococcus aureus are resistant to oxacillin). The etiological structure of nosocomial intra-abdominal infections proves their typical hospital character. Nosocomial pathogens prevail, while in out-of-hospital intra-abdominal infections, the most significant etiological role is played by Escherichia, Protea and Bacteroides.

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

• metronidazole (orally),
• vancomycin (oral)

Prevention of nosocomial infections

Qualitative programs for the prevention of nosocomial infection, based on evidence, can reduce the frequency of their development, the length of stay of patients in the hospital and the cost of treatment. The share of nosocomial infections, the development of which can be prevented by conducting infection control measures, is from 20 to 40%. Infectious control measures should have priority funding.

The following principles must be observed:

• training of personnel,
• epidemiological control,
• interruption of transmission mechanisms,
• elimination of factors of oppression of the patient's anti-infective protection (exogenous and endogenous).

Prevention of nosocomial infections

Risk factors for nosocomial infection	Preventive measures
Congestion of the departments, concentration in the ICU of patients with infections, lack of space and personnel	Isolation of patients with NI, establishment of separate nursing posts Strict adherence to the rules of antiseptic hand hygiene Application of sterile gloves Use of highly effective antiseptics Preferred use of disposable supplies Sterilization and disinfection of high level
Selection of highly resistant strains of pathogens in conditions of widespread use of antimicrobial agents (selective antibiotic pressure)	Establishment of an infection control service in a hospital (clinicians + pharmacies + financially responsible persons) Development of in-hospital protocols and forms Thorough local microbiological monitoring Providing adequate start therapy for severe infections (de-escalation empirical therapy) Adequate dosing of antibiotics, if necessary monitoring of plasma concentrations Compliance with the timing of the antibacterial Therapy Elimination of ineffective drugs Rotation of antibiotics
SKN, translocation of microbes and their toxins in patients in critical conditions	Selective decontamination of the gastrointestinal tract in patients with a high risk of developing NI Indications widespread peritonitis, severe sepsis and PON (any etiology), pancreatic necrosis, liver transplantation
High probability of breakthrough of fungal microflora from endogenous ecotopes in patients in critical conditions	Prophylaxis of systemic candidiasis. Indications: pancreatic necrosis and pancreatic surgery, perforation of the colon, incompetence of the gastrointestinal anastomoses, post-spleenectomy syndrome, prolonged (> 7 days) IVL, prolonged parenteral nutrition, PON immunosuppressive conditions (in particular, long-term glucocorticoid therapy)
Intubation of the trachea and mechanical ventilation	Continuous aspiration of subglottic Half-upright position in bed Prevention distension of the stomach Limiting stress ulcer prophylaxis antacids, oral treatment with chlorhexidine Using techniques to prevent accidental extubation, compliance with the rules of reintubation Restriction of the use of muscle relaxants and CNS depressants Restriction of the indications for nasotracheal intubation (the risk of sinusitis) "Early "tracheostomy, performed in sterile conditions Application closed aspiration Istemi timely removal of any condensate in the circuit use bacterial filters
	Catheterization vessels strictly on indications and deadlines catheterization Compliance contact precautions during catheter (sterile gloves gown mask encasing sterile linen) Maximization of sterility at the site of catheterization Using modern antiseptics with proven efficacy for the treatment of medical personnel hand, injection ports patient's skin Careful maintenance after the place of insertion of the catheter (adequate skin treatment, prevention of moisture accumulation, sterile bandage - gauze transparent or semi-hand label, daily palpation catheterization site or observation through the transparent label) Immediate changing infusion systems after transfusion of blood components and fatliquors
	Quality control of infusion media If there is no evidence of infection, do not perform a routine replacement of the central venous catheter. In case of infection, do not replace the catheter by the conductor (change the catheterization site) Subcutaneous tunneling of the catheter in patients from the high- grade group. Replace catheters installed in an emergency situation without full compliance with the rules aseptic and antiseptic immediately to stabilize the hemodynamics of the patient, but no later than 48 h
Urinary catheters	Training of personnel in catheterization methods Catheterization of the bladder only according to strict indications Strict compliance with aseptic and antiseptic rules during catheterization Intermittent catheterization Using closed drainage systems Providing free urine current Timely replacement of the catheter Failure of routine washing of the drainage system and bladder
	Before treatment with an antiseptic, the operating field should be cleaned with a detergent. Antiseptics with proven efficacy should be used to prepare the skin of the operating field. Glucose levels should be adequately monitored in all patients with diabetes, especially avoiding hyperglycemia in the perioperative period. Perioperative antibacterial prophylaxis should be prescribed only according to the indications of the risk of developing infectious complications and choose the drug for its conduct, based on its activity against the most more common pathogens of infection areas of the operation with specific interventions and on published recommendations Surgical aspects of infection prevention area of operation effective hemostasis, prevention of hypothermia,
Surgical interventions	Preparing the operating room Equipping air ventilation with positive pressure of sufficient power Air filtration Maintaining an optimal microclimate (temperature 18-24 С, humidity 50-55%) Closed doors and windows mode Reasonable limitation of the number of personnel Do not apply sticky mats at the entrance to the operating and ultraviolet radiation for prophylaxis infections in the operation Preparing the operating room and anesthetic teams obligatory scrubs, a mask and a hat, completely closing hair hand hygiene rules non-use of brushes and sponges before each use sterile high quality gloves using two pairs of gloves in a number of interventions (orthopedic surgery, sternotomy) suspended from operation personnel with symptoms of common infectious diseases and infectious skin lesions Preparation patient Whenever it is possible, it is necessary to identify and treat all infections other than the area of intervention, localization. Do not remove the hair from the operating field Except when it is likely to interfere with operations if necessary - to remove the scalp immediately prior to hair removal machines must be used and depilatories instead shaver
Intravascular / intracardiac catheters and implants	Training of personnel in the rules of working with catheters, devices and care for them, periodic assessment of knowledge of aseptic and antiseptic rules, skills of catheterization and catheter care
	careful treatment of tissues, removal of non-viable tissues adequate use of drains and suture material elimination of small cavities, competent care for the operating wound

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

• modern architectural and technical solutions,
• epidemiological surveillance (or monitoring) of nosocomial infection,
• isolation of patients with purulent-septic complications,
• the introduction of the principle of a minimum number of patients per sister,
• reduction of the preoperative period,
• creation of federal and local protocols and forms,
• application of highly effective antiseptics (or antiseptics with proven efficacy),
• strict adherence to the rules of hand hygiene,
• conducting high-quality sterilization and disinfection,
• training of personnel in the rules of working with invasive devices and devices, periodic assessment of knowledge of aseptic and antiseptic rules, catheterization and catheter care skills,
• removal of invasive devices immediately after the disappearance of clinical indications for their use,
• application of invasive devices with antimicrobial and anti-biofilm coating.