1. Institute for Microbiology, Medical Faculty of Masaryk University and St. Anna Faculty Hospital in Brno Miroslav Votava Agents of nosocomial (hospital- acquired) infections The last lecture for 3rd-year students The last lecture for 3rd-year students 14 th December, 2012

2. Congenital and neonatal infections, definitions – revision Congenital infections =Congenital infections = = intrauterine infections = = prenatal infections perinatal infections (closely perinatal infections (closely before and during the before and during the delivery) delivery) Neonatal infectionsNeonatal infections postnatal infections (up to 4 postnatal infections (up to 4 weeks of life) weeks of life) Congenital and neonatal infections are caused by agents unusual in older childrenCongenital and neonatal infections are caused by agents unusual in older children

3. A little bit of immunology – revision Fetus = an immunological paradox Fetus and mother = two immune systems To be able to get on well, both must be modulated „Fetal immunodeficiency“ 1.Inability to produce cytokines 2.Defects in intracellular killing 3.Immature production of antibodies

4. The protection of the fetus – revision Placenta and amnionPlacenta and amnion Maternal IgG (halftime = 20 days)Maternal IgG (halftime = 20 days) –actively transported through the placenta –IgG against capsular polysaccharides are active only up to circa 3 months after delivery –IgG against viruses are effective even up to 12-15 months Colostral IgAColostral IgA

5. Prenatal infections – revision Agent Trimester Congenital defects Postnatal persistence 1.2.3. Treponema pallidum -++++ List. monocytogenes --+-- Rubella virus +++-++ CMV+++++ Parvovirus B19 ±+±-- VZV+-+±+ HSV+++-+ HIV···-+ Toxoplasma gondii ±+++++

6. Diagnostics of prenatal infection – revision Examination of mother – immensely important in syphilis (obligatory in most countries) and in toxoplasmosis Examination of the newborn – above all the detection of its IgM (IgM antibodies cannot be of maternal origin – they don’t pass through the placenta) – sometimes the direct detection (e.g. CMV in urine)

7. Treatment & prevention of prenatal infection – revision Treatment (of the mother): PNC in syphilis spiramycin in toxoplasmosis Prevention: healthy mother (examined for syphilis, possibly for toxoplasmosis)

8. Infections proceeding more severely in pregnancy – revision Malaria – because of lower cellular immunity Virus hepatitis – especially VHE Influenza – during pandemics Poliomyelitis – more frequent paralysis Urinary tract infections – pressure on the ureter, atonia of urinary bladder Candidosis – vulvovaginitis Listeriosis – beware of cheese

9. Perinatal infections – revision „Immunologic immaturity and naivety of the newborn“ Inability to produce antibodies against polysaccharides Low level of complement and few NK cells Small supply of neutrophils Insufficient function of neutrophils Low level of IgA (particularly in premature infants) Low mucosal immunity (Satisfactory cellular immunity)

10. Agents transmissible during delivery – revision Agents originating in vagina, cervix and rectum:Agents originating in vagina, cervix and rectum: GBS – sepsis and meningitis (early and late one) Chl. trachomatis D – K – inclusion conjunctivitis E. coli & other enteric rods – sepsis and meningitis Neisseria gonorrhoeae – purulent conjunctivitis Listeria monocytogenes – meningitis and sepsis Haemophilus influenzae – meningitis and sepsis Mycoplasma hominis – pneumonia? Candida albicans – soor (thrush) HSV-2 – generalized herpes Agents originating in blood:Agents originating in blood: HBV, HIV

11. Agents transmissible postnatally – revision From the mother:From the mother: group B streptococci – sepsis and meningitis Staphylococcus aureus – pyodermia, even sepsis Mycobacterium tuberculosis – tuberculosis CMV – ? HIV – AIDS From the surrounding environment:From the surrounding environment: enterobacteriae incl. salmonellae – diarrhoea and sepsis Pseudomonas aeruginosa – serious diarrhoea Staphylococcus aureus – pyodermia, even sepsis respiratory syncytial virus (RSV) – bronchiolitis

12. Diagnostics of perinatal and postnatal infections – revision The most rapid methods are essential – therefore direct detection only Microscopy – invaluable in CSF (Cocci or rods? G+ or G– ? In clumps, chains, or in pairs?) Detection of antigens – CSF again: GBS, HIB, pneumococci, meningococci (group B ~ E. coli K1) PCR – not yet standardized

13. Prevention of perinatal and postnatal infections – revision Screening of the mother (examination of vaginal and rectal swab for GBS) Prevention of premature labour (because of immune immaturity of the newborn) Leading the delivery lege artis (examination per rectum, induction of labour after the rupture of membranes etc.) Clean and tidy delivery room and the newborn ward …

14. Definition of NI Nosocomial infections = = infections originated in connection with the stay in hospital (as distinct from infections originated in the community) At least 5 % patients are afflicted by NI, but probably more Exogenic NI: source = other patients, staff, environment vector = in most cases the staff’s unwashed hands Endogenic NI: source = the patient himself

15. Consequences of NI Increased mortality (†) – up to 40 % (rough estimate in this country amounts to hundreds deaths per year) Prolonged hospitalization (by weeks) and increased cost (by tens of thousands or more Czech crowns per case) Economic loss circa 1.5 miliiard CZC per year Additional ATB therapy (both cost and toxicity) Patients = the source of infection for others And the same time >1/3 NI can be prevented!

16. Main kinds of NI 1.Urinary infections of catetherized patients – up to 40 % of all NI 2.Respiratory infections – about 20 % –Early ventilator pneumonia –Late ventilator pneumonia –Aspiration pneumonia –Other respiratory infections 3. Suppurative infections of surgical wounds – about 20 % 4. Bloodstream Infections (sepsis from inserted intravenous catheters) – at least 15 %

17. Etiology of urinary NI Escherichia coli 25 % other enterobacteriae 20 % enterococci 15 % Pseudomonas aeruginosa 10 % other G– non-fermenting rods 10 % candidae 5 %

18. Etiology of respiratory NI – I Early ventilator pneumonia: Staphylococcus aureus 25 % Streptococcus pneumoniae 20 % Haemophilus influenzae 15 % enterobacteriae 10 % other aerobically growing bacteriae 5 % anaerobes 1 % (monomicrobial etiology, agent originates from the community)

19. Etiology of respiratory NI – II Late ventilator pneumonia: G– non-fermenting rods40 % (P. aeruginosa, Acinetob. baumannii) enterobacteriae30 % (klebsiellae, E. coli, enterobacters) staphylococci20 % (above all S. aureus) yeasts 5 % (some cases have polymicrobial etiology, agents are of hospital origin)

20. Etiology of respiratory NI – III Aspiration nosocomial pneumonia: Older works emphasized anaerobes Newer studies trace the same etiology as in ventilator pneumonias and emphasized Gram-negative rods (non-fermenting ones rather than enterobacteriae) Affliction of lungs in febrile neutropenia: First days: 2 × more often G+ cocci (staphylococci, pneumococci) than G– rods (enterobacteriae and pseudomonads) Later on: ↓ G+ cocci, ↑ candidae and aspergills After an allogenic transplantation of bone marrow: mainly CMV

21. Etiology of surgical wounds suppuration (It depends on the terrain in which the surgery took place) Staphylococcus aureus coagulase-negative staphylococci Streptococcus pyogenes enterobacteriae bacteroids, prevotellae, peptostreptococci gramnegative non-fermenting rods Clostridium perfringens

22. Etiology of sepsis from i.v. catheters Coagulase-negative staphylococci (>50 %) – because of the biofilm production enterococci Staphylococcus aureus enterobacteriae (E. coli, klebsiellae) Pseudomonas aeruginosa Acinetobacter spp. Candida spp.

23. Etiology of nosocomial viroses Influenza v. – esp. infants and older patients RSV – newborns and suckling infants adenoviruses – eye departments Other respiratory viruses CMV – after the cytotoxic therapy rotaviruses – esp. children HBV – higher risk with prologed stay HIV – fortunately not in this country

24. Predispozition to NI Age – both extremes of the age Therapy – cytotoxic therapy, steroids, antibiotics Basic illness affliction of the liver diabetes mellitus tumors affliction of the kidneys and bladder skin lesions Trauma – incl. surgical wounds and i.v. catheters

25. Prevention of NI – I Four main strategies: 1.Elimination of sources of infection from the hospital environment 2.Breaking the epidemic chain (the way of spreading the infection from the source to the host ) 3. Strengthening the resistance of the host to the infection 4. Investigating the causes of NI

26. Prevention of NI – II 1.Elimination of sources of infection from the hospital environment from the hospital environment Sterile instruments, dressings, medicines, fluids for infusions, duly examined blood for transfusions, clean linen, noncontaminated foodSterile instruments, dressings, medicines, fluids for infusions, duly examined blood for transfusions, clean linen, noncontaminated food Prevention of contact with infected staff – an acutely ill or a carrier of pathogensPrevention of contact with infected staff – an acutely ill or a carrier of pathogens

27. Prevention of NI – III 2. Breaking the epidemic chain EquipmentEquipment –ventilation (air conditioning and legionellae, building works and aspergills) –water (legionellae) –Patient‘s isolation For his/her protectionFor his/her protection For the vicinity protectionFor the vicinity protection PeoplePeople –Support of aseptic behavior of staff –The most important is effective hand washing

28. Prevention of NI – IV 3. Strengthening the host resistance ImmunizationImmunization –influenza (older patients) –pneumococcal infections (before transplantation, before splenectomy) –VHB (in seronegative persons before dialysis) –VZV infections (specific Ig in immunocompromised) ATB prophylaxisATB prophylaxis –In “dirty” surgery –in orthopaedics, cardiosurgery, neurosurgery Lowering the risk of infectionLowering the risk of infection –Proper technique –Meticulous care of invasive aids and infusions –Prevention of decubites

29. Prevention of NI – V 4. Investigating the causes of NI Surveillance (= detailed monitoring) – records changes in numbers or types of NISurveillance (= detailed monitoring) – records changes in numbers or types of NI Examination of individual cases of NI, esp. if they have an epidemic characterExamination of individual cases of NI, esp. if they have an epidemic character Formulation of antiepidemic principles and monitoring how they are observedFormulation of antiepidemic principles and monitoring how they are observed…

30. Homework 12 Austrian artist Ivo Saliger (1894– 1987): The Physician Struggling with the Death for a Young Girl (1920)

31. Homework 12 Successful homework 12 solver: None (but thanks for the effort)

32. Homework 13 The gouache of a Czech artist is a part of the cycle named after an infectious disease – which one?

33. Answer and questions The solution of the homework and possible questions please mail (on Monday 6.30 a.m. at the latest) to the address mvotava@med.muni.cz Thank you for your attention Good luck at the examination!