2024-2025 Microbiology Lecture Slides (PDF)

Dr Jorge Garcia-Lara MICROBIOLOGY Unit: ISCM Module: UM2010 Yr. 2024-2025 More on Paediatric IDs Neonatal infections by : LECTURE 4...

Dr Jorge Garcia-Lara MICROBIOLOGY Unit: ISCM Module: UM2010 Yr. 2024-2025 More on Paediatric IDs Neonatal infections by : LECTURE 4 CORE Dr. GARCIA-LARA Bitesize 1 SLIDES School of Medicine Medicinae Baccalaureus Baccalaureaus Chirurgiae (MBBS) Physician Associate Studies (MPAS) 1  Dr Jorge Garcia-Lara Activity Infectious disease in autoimmune conditions, genetic disorders, geriatric and paediatric stages Review and compile last year’s information: urinary, respiratory, …, infections in children and older adults Submission : N/A Contributors : Individual / Study group Output : N/A School of Medicine Medicinae Baccalaureus Baccalaureaus Chirurgiae (MBBS) Physician Associate Studies (MPAS) 2  Dr Jorge Garcia-Lara Bordetella pertussis : Whooping cough 3  Dr Jorge Garcia-Lara Paediatric infectious diseases UPPER RESPIRATORY TRACT SKIN & SOFT TISSUE INFECTIONS VIRAL INFECTIONS INFECTIONS Impetigo ✓ Herpes simplex ✓ Influenza ✓ Eczema ✓ Varicella zoster ✓ Acute Sore Throat ✓ Cellulitis ✓ Herpes zoster ✓ Acute Otitis Media ✓ Wound Infections (Non surgical) Prophylaxis Advice: High Risk Contacts Acute Otitis Externa ✓ Bites of Patients with Chickenpox or Shingles Acute Rhinosinusitis ✓ Human HEPATITIS ✓ Dental Abscess Cat or Dog HEPATITIS B ✓ Oral Candidiasis ✓ Acne Vulgaris ✓ HEPATITIS C ✓ Oral Candidiasis - Breastfed Infant Neonatal & Infantile Acne Boils / Cysts/ Abscesses / Carbuncles ✓ EYE INFECTIONS LOWER RESPIRATORY TRACT Paronychia Conjunctivitis ✓ INFECTIONS Scabies Styes Community Acquired Pneumonia ✓ Head Lice Exacerbation of Bronchiectasis MENINGITIS (excluding cystic fibrosis). FUNGAL SKIN INFECTIONS Bacterial Meningitis and / or ✓ Pertussis treatment Pertussis prophylaxis ✓ Fungal / Dermatophyte infection of the skin – Dermatophytes ✓ Suspected Meningococcal Disease Meningococcal Meningitis Prophylaxis Fungal / Dermatophyte infection of the URINARY TRACT INFECTIONS skin - Scalp Dermatophytes ✓ ASPLENIA UTI in Children ✓ Fungal / Dermatophyte infection of the Prophylaxis for Asplenia Recurrent UTIs in Children proximal fingernail or toenail ✓ Asymptomatic bacteruria ✓ Pityriasis Versicolor ✓ GASTRO-INTESTINAL TRACT Repeat (surveillance) specimens INFECTIONS Gastroenteritis/ Infectious Diarrhoea ✓ GENITAL TRACT INFECTIONS ✓ Clostridium difficile Infection (CDI ✓ Giardia ✓ Threadworms ✓ Other Worms ✓ 4  Dr Jorge Garcia-Lara MICROBIOLOGY Unit: ISCM Module: UM2010 Yr. 2024-2025 by : LECTURE 4 CORE Dr. GARCIA-LARA Bitesize 2 SLIDES School of Medicine Medicinae Baccalaureus Baccalaureaus Chirurgiae (MBBS) Physician Associate Studies (MPAS) 5  Dr Jorge Garcia-Lara Neonatal infections worldwide, more than 40% of deaths occur within the neonatal period, i.e., 3.1 million newborn deaths each year the majority in low-income countries Listeria monocytogenes J. Lister E.G.D. Murray H. Pirie School of Medicine Medicinae Baccalaureus Baccalaureaus Chirurgiae (MBBS) Physician Associate Studies (MPAS) 6  Dr Jorge Garcia-Lara ? Harvey Pirie 7  Dr Jorge Garcia-Lara Listeriosis rare, mainly newborn infants, the elderly & immunocompromised Ubiquitous in the environment (soil, wood & decaying matter) foodborne zoonosis (fatal to animals too) typically, ingestion through contaminated food asymptomatically carried in GI or vagina (pregnancy problem) transplacental transmission to foetus Gram-positive rod 8 8  Dr Jorge Garcia-Lara Listeriosis JOSE A. VAZQUEZ-BOLAND et. al. 2001. Clinical Microbiology Reviews 9 9  Dr Jorge Garcia-Lara Listeriosis mothers asymptomatic or may experience influenza-like illnesses (headache, malaise, fever, backache, nausea, vomiting, diarrhea, and chills) mothers may undergo premature labour (possible stillbirth) newborn respiratory distress poor feeding fever seizures (maybe) Granulomatosis infantisepticum / infantiseptica(surface and internal) erythematous rash small, pale nodules or granulomas Granulomatosis infantisepticum Granulomatosis infantisepticum 10 10  Dr Jorge Garcia-Lara Listeriosis, similar presentation to other neonatal pathogens (e.g., E. coli & GBS) School of Medicine Medicinae Baccalaureus Baccalaureaus Chirurgiae (MBBS) Physician Associate Studies (MPAS) 11  Dr Jorge Garcia-Lara MICROBIOLOGY Unit: ISCM Module: UM2010 Yr. 2024-2025 Neonatal infections SEPSIS by : LECTURE 4 CORE Dr. GARCIA-LARA Bitesize 3 SLIDES School of Medicine Medicinae Baccalaureus Baccalaureaus Chirurgiae (MBBS) Physician Associate Studies (MPAS) 12  Dr Jorge Garcia-Lara Neonatal infections mainly sepsis, meningitis and pneumonia sepsis : a crucial problem clinical (management) technical –diagnosis-; non-specific symptoms, laboratory time-consuming US 2 in 1000 live births (i.e., 270,000 / year) had sepsis; similar in UK of the approx. 15% evaluated for neonatal sepsis only ½ have culture-proven sepsis e.g., in a subset of Egyptian hospitals (18mo. 2011-2012) 50% of ICU admitted newborns had sepsis, ½ of them Early Onset (EOS; 72h) mortality rate on proven neonatal sepsis >50% (in the Egypt study, but applicable to developed countries) El-Din, et al., 2015. Epidemiology of neonatal sepsis and implicated pathogens: a study from Egypt. Biomed. Res Int. 13  Dr Jorge Garcia-Lara Neonatal infections : common infective agents non-STDs : E. coli, staphylococci (S. aureus, S. epidermidis –CoNS-, S. agalactiae (GBS), Listeria monocytogenes, H. influenzae, Klebsiella, Pseudomonas, Enterobacter, Candida, Serratia, Acinetobacter, anaerobes STDs : gonorrhoea, syphilis, HSV, CMV, hepatitis, rubella, toxoplasma, HIV, hepatitis, trichomoniasis, “candidiasis” GBS; sepsis, pneumonia, meningitis Listeriosis; pneumonia, sepsis, meningitis E. coli ; UTIs, pneumonia, sepsis, meningitis Candidiasis; diaper rash, oral thrush Congenital infections; HIV, rubella, chickenpox, syphilis, herpes, toxoplasmosis, CMVs Conjunctivitis Camacho-Gonzalez et al. 2013. Neonatal Infectious Diseases: Evaluation of Neonatal Sepsis. Pediatr Clin North Am. 60(2):367-389. 14  Dr Jorge Garcia-Lara Many neonatal infections have similar symptoms poor feeding breathing difficulty listlessness decreased or elevated temperature unusual skin rash or change in skin color persistent crying unusual irritability mnemonic Activity F, … B, … L, … T, … S, … C, … I, … 15 15  Dr Jorge Garcia-Lara Neonatal infections Risk factors for early-onset (EO) neonatal infection, including 'red flags’ (mainly in the mother) Risk factor Red flag Invasive group B streptococcal infection in a previous baby (mother) Maternal group B streptococcal colonisation, bacteriuria or infection in the current pregnancy Prelabour rupture of membranes Preterm birth following spontaneous labour (before 37 wks gestation) Suspected or confirmed rupture of membranes for more than 18 hours in a preterm birth Intrapartum fever higher than 38°C, or confirmed or suspected chorioamnionitis Parenteral antibiotic treatment given to the woman for confirmed or suspected invasive bacterial infection (such as septicaemia) at any time during labour, or in the 24-hour periods before and after the birth Yes [This does not refer to intrapartum antibiotic prophylaxis] Suspected or confirmed infection in another baby in the case of a multiple pregnancy (THIS IS IN THE BABY) Yes 16  Dr Jorge Garcia-Lara Neonatal Clinical indicators of possible early-onset infection (EO) neonatal infection (baby observations) Clinical indicator Red flag s Altered behaviour or responsiveness Altered muscle tone Feeding dificulties or intolerance Abnormal heart rate (bradycardia or tachycardia) Signs of respiratory distress Hypoxia (e.g., cyanosis)* or apnoea*, respiratory distress >4 hours after birth, Yes Jaundice within 24 hours of birth Signs of neonatal encephalopathy* and seizures Yes Need for cardio–pulmonary resuscitation Need for mechanical ventilation in a preterm* or term baby Yes Persistent fetal circulation (persistent pulmonary hypertension) Temperature abnormality (38°C) unexplained by environmental factors Signs of shock Yes Unexplained excessive bleeding, thrombocytopenia, or abnormal coagulation Oliguria persisting beyond 24 hours after birth Altered glucose homeostasis (hypoglycaemia or hyperglycaemia) Metabolic acidosis Local signs of infection (for example, affecting the skin or eye) 17 * None of them in isolation is a red flag  Dr Jorge Garcia-Lara MICROBIOLOGY Unit: ISCM Module: UM2010 Yr. 2024-2025 GBS by : LECTURE 4 CORE Dr. GARCIA-LARA Bitesize 3 SLIDES School of Medicine Medicinae Baccalaureus Baccalaureaus Chirurgiae (MBBS) Physician Associate Studies (MPAS) 18  Dr Jorge Garcia-Lara Group B streptococcus (GBS) : major perinatal pathogen the most common cause of neonatal bacterial sepsis (and meningitis) identified in developed countries El-Din, et al., 2015. Epidemiology of neonatal sepsis and implicated pathogens: a study from 19 Egypt. Biomed. Res Int.  Dr Jorge Garcia-Lara The BABY HAS/HAD A POST NATAL GBS infection If concerns about early-onset neonatal infection before a baby is discharged: - advise parents/carers verbally and in writing that they should seek medical advice if they are concerned that the baby: is showing abnormal behaviour (e.g., inconsolable crying or listlessness) or is unusually floppy or has developed feeding difficulties or has an abnormal temperature unexplained by environmental factors (lower than 36°C or higher than 38°C) or has rapid breathing or has a change in skin colour 20 https://www.nice.org.uk/guidance/cg149/chapter/1-guidance  Dr Jorge Garcia-Lara THE BABY NEEDS ANTIBIOTICS it should be given as soon as possible always within 1 hour of the decision to treat (a sepsis paradigm) 21 https://www.nice.org.uk/guidance/cg149/chapter/1-guidance  Dr Jorge Garcia-Lara Risk factors & clinical indicators THE BABY MAY NEED ANTIBIOTICS ? (to direct antibiotic management) babies with … no red flags 2 or more any red flags 1 risk factor or ‘non-red flags 1 clinical indicator perform investigations is it safe to withhold o CRP before starting antibiotics antibiotics? 18–24 hours after presentation o blood culture (e.g., if umbilical infection) is it necessary to o lumbar puncture (signs/symptoms of monitor the infection/meningitis; +ve CRP, +ve blood culture,non responsive to antibiotic) baby's vital signs and o test for Chlamydia, gonorrhoea (if purulent clinical condition eye discharge) o NOT routine urine microscopy/culture start antibiotic treatment https://www.nice.org.uk/guidance (even w/o lab results) /cg149/chapter/1-guidance 22  Dr Jorge Garcia-Lara THE BABY MAY NEED ANTIBIOTICS ? babies with … 2 or more any red flags ‘non-red flags AVOID routine use of antibiotics 36 hours after antibiotics in the baby consider stopping the antibiotics at 36 hours if: the blood culture is -ve, and the initial clinical suspicion of infection was not strong, and the baby has no clinical indicators of infection, and the levels/trends of C-reactive protein are reassuring 23  Dr Jorge Garcia-Lara Neonatal infections SUSPECTED INFECTION ANTIBIOTICS i.v., benzylpenicillin + gentamicin (depending on bacterial resistance) flucoxacillin + gentamicin (umbilical cord infections) amoxycillin + cefotaxime (meningitis with G-ve unknown pathogen) amoxicillin + gentamycin (if Listeria) think of: gentamycin as the antibiotic of choice for G-ves cefotaxime the antibiotic of choice for G+ves (Amox. also good) If there are G-ves keep gentamicin plus e.g., cefotaxime If no G-ves stop gentamicin If no G+ves stop amoxicillin If Listeria STOP cefotaxime INSTEAD amoxicillin If G-ves or staphylococci, you may need to increase gentamicin 24 https://www.nice.org.uk/guidance/cg149/chapter/1-guidance  Dr Jorge Garcia-Lara Neonatal infections PROPHYLACTIC ANTIBIOTICS, when? Intrapartum antibiotics (TO PREVENT EARLY ONSET [EO] NEONATAL INFECTION) if women had: for women in preterm labour if o a previous baby with an invasive there is: GBS infection prelabour or o GBS colonisation intrapartum rupture of o bacteriuria membranes o infection in current pregnancy i.v., benzylpenicillin clyndamicin if pen allergy 25 https://www.nice.org.uk/guidance/cg149/chapter/1-guidance  Dr Jorge Garcia-Lara Neonatal infections when it comes down to antibiotic selection & regimes besides the results of microbiological investigations amongst the expert microbiological advice take into account local surveillance data 26 https://www.nice.org.uk/guidance/cg149/chapter/1-guidance  Dr Jorge Garcia-Lara The BABY HAD GBS infection if woman becomes pregnant AGAIN: increased risk of EO neonatal infection she should inform her maternity care team that a previous baby had a GBS infection antibiotics in labour recommended should be advised as to potential long-term effects of the baby's illness and likely patterns of recovery risk of: recurrence of GBS infection in the baby GBS infection in future babies 27  Dr Jorge Garcia-Lara The WOMAN HAD GBS COLONISATION IN PREGNANCY, NOT THE BABY if she becomes pregnant again, this will not affect the birth management colonization ≠ infection School of Medicine Medicinae Baccalaureus Baccalaureaus Chirurgiae (MBBS) Physician Associate Studies (MPAS) 28  Dr Jorge Garcia-Lara Other guidelines to look into Caesarean section. NICE clinical guideline 132 (2011). Bacterial meningitis and meningococcal septicaemia. NICE clinical guideline 102 (2010). Induction of labour. NICE clinical guideline 70 (2008). Antenatal care. NICE clinical guideline 62 (2008). Intrapartum care. NICE clinical guideline 55 (2007). Update in progress. Publication date to be con rmed. Urinary tract infection in children. NICE clinical guideline 54 (2007). Feverish illness in children. NICE clinical guideline 47 (2007). Update in progress. Publication expected May 2013. Postnatal care. NICE clinical guideline 37 (2006). 29  Dr Jorge Garcia-Lara MICROBIOLOGY Unit: ISCM Module: UM2010 Yr. 2024-2025 Geriatric Infectious disease by : LECTURE 4 CORE Dr. GARCIA-LARA Bitesize 4 SLIDES School of Medicine Medicinae Baccalaureus Baccalaureaus Chirurgiae (MBBS) Physician Associate Studies (MPAS) 30  Dr Jorge Garcia-Lara Geriatric population / the elderly – Geriatrics part of medicine Cut-off not precise, >50, >60, >70 Increased no. of people >65 yr old 1900, 1% earth’s population >65, 15 mill. 1992, 6% earth;s population >65, 342mill. 2050, 2.5 bill. greatly diverse health status complicates the medical picture Risk Factors 1) lifestyle, e.g., nursing homes, leisure travel, volunteer work, visits to the clinic/hospital, … ? 31  Dr Jorge Garcia-Lara 2) decreased immunity Compromised immunocompetence (impaired host defences): immune senescence: T-lymphocyte production & proliferation decline with age (= decreased CMI & antibody production to new antigens) Low CMI (Cellular Mediated Immunity), a predisposing factor for: TB higher rates of latent infection (from an era of high TB incidence) most common notifiable diseases in the >65 isoniazid prophylaxis has greater risks for the elderly nosocomial infections changes in non-adaptive immunity (thinning skin, enlarged prostate, diminished cough reflex, and other anatomic or physiologic accompaniments ) chronic disease medications malnutrition functional impairments (e.g., immobility, incontinence, dysphagia, catheterization) 32  Dr Jorge Garcia-Lara HCAI (Health Care Associated Infections) Amongst adults, older adults 1st to be affected by new/emerging infections (HA- or HCAI) Risk for HA Risk HCAI: share common sources of air, food, water hygienic practices in the elderly (age or culture) contact with children and grandchildren health care in nursing homes … HCAI - Infection control measures essential: infection surveillance rigorous infection control practice isolation practices handwashing sterile techniques and other procedures 33  Dr Jorge Garcia-Lara HCAI – additional link to Long-Term Facilities is a challenge, in large part because discharging patients is not an option for control additional control measures mentioned on HCAIs: decubitus ulcers proper catheter use tetanus vaccine for injury-prone residents any pneumonia considered as potential tuberculosis 34  Dr Jorge Garcia-Lara HCAI HCAI most frequent infections (in geriatric patients): Respiratory & GI Outbreaks are common 6% of outbreaks occurred in long-term care facilities (CDC's Hospital Infections Program) Relocation between nursing homes helps transfer antimicrobial resistance (AMR) – and it will continue happening School of Medicine Medicinae Baccalaureus Baccalaureaus Chirurgiae (MBBS) Physician Associate Studies (MPAS) 35  Dr Jorge Garcia-Lara Nosocomial infections not present on admission to a hospital but develop after the 3rd hospital day (72h) not one specific infection the elderly have the highest rates of nosocomial : UTIs infected surgical wounds pneumonia and bacteremia 36  Dr Jorge Garcia-Lara Pneumonia School of Medicine Medicinae Baccalaureus Baccalaureaus Chirurgiae (MBBS) Physician Associate Studies (MPAS) 37  Dr Jorge Garcia-Lara Common respiratory diseases : o e.g.. influenza (A,B), RSV, coronavirus, parainfluenza virus, & rhinovirus o Pneumonia (S. pneumoniae and TB) Also not common respiratory pathogens: Legionella variants Some re-emerging pathogens like Cryptosporidium or Chlamydia pneumoniae, … foodborne outbreaks of gastroenteritis caused by Salmonella spp. and Campylobacter jejuni Streptococcus pyogenes - the "flesh-eating" bacterium Other types : UTIs, salmonellosis, bacteraemias and hepatitis Pneumococcal disease (S. pneumoniae): important risk factor for the elderly most common ofCA-pneumonia in the elderly (60 % of cases) elderly = highest pneumococcal bacteremia rates 38  Dr Jorge Garcia-Lara pneumococcal costs of pneumococcal diseases are high: the elderly require hospitalization the illnesses often cause complications pneumococcal pneumonia does not result in permanent lung damage, but complications from bacteremia and meningitis are: common can damage other organ systems antibiotics are considered to be effective in pneumococcal diseases but deaths and complications often occur School of Medicine Medicinae Baccalaureus Baccalaureaus Chirurgiae (MBBS) Physician Associate Studies (MPAS) 39  Dr Jorge Garcia-Lara Pneumococcal polysaccharide vaccine 1st developed in the 1940’s –abandoned b/c advent of antibiotics b/c of AMR – introduced again in the 1970s capsular vaccine – antibody-based immunity: PCV13 (Prevenar 13 - 13-valent) PPSV23 (Pneumovax – 23-valent) – recommended for the >65 !!! efficacy varies between studies: from 0 to 70% protection Recommendations US to administer it to >65 less effective in immunosuppressed more vaccines need to be developed https://wwwnc.cdc.gov/eid/article/5/3/99-0304_article 40  Dr Jorge Garcia-Lara Pneumococcal polysaccharide vaccine PATHOGEN REPLACEMENT ISSUE (H. influenzae and S. pneumoniae vaccines) S. pneumoniae type 19A (not included in PCV7 but included in PCV13) emerged as the most common cause of pneumococcal disease in children and adults a few years after universal vaccination with PCV7 began in the US “Existing pneumococcal vaccines utilize capsular polysaccharides as antigens. Vaccines cannot include all serotypes ! replacement strains appear pneumococci readily acquire DNA from other microorganisms by transformation, giving them the ability to switch capsular serotypes attempts to develop vaccines based on highly conserved proteins (eg, pneumolysin, histidine triad protein D, surface proteins A and C), some of which are surface expressed and one of which (pneumolysin) contributes substantially to the pathogenesis of pneumococcal disease in development ! 41  Dr Jorge Garcia-Lara AMR School of Medicine Medicinae Baccalaureus Baccalaureaus Chirurgiae (MBBS) Physician Associate Studies (MPAS) 42  Dr Jorge Garcia-Lara AMR strains a problem in nursing homes multidrug resistance (MDR) G-ve uropathogens methicillin-resistant S. aureus (MRSA) have received the most attention Gram-negative enteric bacilli have become resistant to fluoroquinolones and extended-spectrum cephalosporins vancomycin-resistant enterococci penicillin-resistant pneumococci Guidelines address: infection control programs Influenza antimicrobial use antimicrobial resistant pathogens 43  Dr Jorge Garcia-Lara Influenza School of Medicine Medicinae Baccalaureus Baccalaureaus Chirurgiae (MBBS) Physician Associate Studies (MPAS) 44  Dr Jorge Garcia-Lara Influenza Influenza A and/or Influenza B Influenza epidemics occur every year, usually in the winter (more stable in cold air and low humidity). staggering pneumonia (viral and bacterial) medical costs cardiac respiratory failure Hospitalizations aggravate preexisting conditions loss of productivity e.g., diabetes or asthma. mortality leads all and to other illness (morbidity and costs) lengthy periods are needed to recover from influenza the elderly have the highest hospitalization and death rates from influenza (80-90%) >20,000 deaths from influenza in the US 45  Dr Jorge Garcia-Lara Influenza inactivated virus vaccines are tri-/quadri-valent, with two type A and one type B strains, & contain egg-grown viruses compromised efficiency b/c changing viruses and.declining antibody levels 70 % effective (influenza illness prevention) the remaining 30 percent will suffer a milder influenza illness less immunogenic in the immunosuppressed elderly currently several candidate live virus vaccines (safe, easy to administer, and capable of longer-lasting protection) for immunized immunosuppressed persons and for persons unable to take vaccines, antiviral prophylaxis/treatment: amantadine (Influenza A ) Influenza and pneumococcal vaccines still safe and effective when given simultaneously !!! 46  Dr Jorge Garcia-Lara And if leaving aside pneumococcal disease, influenza, TB, and nosocomial infections … Fever of unknown origin (FUOs) not unusual for the elderly and often results in lengthy and costly evaluations endocarditis valvular heart conditions known to predispose an individual to endocarditis should receive antibiotic prophylaxis for any procedure known to cause bacteremia more expedient and less expensive methods of diagnosing the causes of such fevers are needed infectious diarrhea, meningitis, urosepsis, and pressure sores are other examples of infections in the elderly for which better methods of prevention are needed. 47  Dr Jorge Garcia-Lara MICROBIOLOGY Unit: ISCM Module: UM2010 Yr. 2024-2025 IDs on those with physiological dysfunctions by : LECTURE 4 CORE Dr. GARCIA-LARA Bitesize 5 SLIDES School of Medicine Medicinae Baccalaureus Baccalaureaus Chirurgiae (MBBS) Physician Associate Studies (MPAS) 48  Dr Jorge Garcia-Lara Risk factors (for opportunistic infections) Extrinsic factors Intrinsic factors age pathogen exposure (community, nosocomial) immune deficit HIV (neutrophil, T cell B cell) radiation, drugs and surgery dose & duration of treatment defect duration & severity cytopenias (issues post-transplant) neutropenia, leukemia, … metabolic dysfunction malnutrition DM organ dysfunction anatomic abnormalities HSCT genetic disorders lung transplant prolonged ischemia liver transplant fulminant hepatic/renal failure renal transplant prolonged hemodialysis pancreas transplant enteric drainage 49  Dr Jorge Garcia-Lara Forbes et al. 2016. The Gut Microbiota in Immune-Mediated Inflammatory Diseases. Front Microbiol. 7:1081. McKay et al. 2016. Factors associated with onset, relapses or progression in multiple sclerosis: A systematic review. Neurotoxicology. Epub ahead of print. 50  Dr Jorge Garcia-Lara Helicobacter pilori School of Medicine Medicinae Baccalaureus Baccalaureaus Chirurgiae (MBBS) Physician Associate Studies (MPAS) 51  Dr Jorge Garcia-Lara The H. pylori link with physiol. dysfunct. H. pylori prevalence in patients with Diabetes type I or II o effectiveness of H. pylori eradication lower in diabetics changes in gastric microvasculature leading to reduced antibiotic absorption ? resistant H. pylori ? o reinfection rates higher in patients with DM (particularly Type I) o dyslipidemia and thyroid autoimmune diseases, increasing evidence o DM, obesity and osteoporosis – remains controversial o vaccine development – the way to go ?!? 52  Dr Jorge Garcia-Lara trigger metabolic dysfunctions/ microorganism genetic/immune deficiencies target What is the link between diabetes, thyroid diseases, lipidemia,..., and infectious disease 53  Dr Jorge Garcia-Lara H. pylori , endocrinology, chicken and eggs Chronic gastritis acute inflammatory ½ world PUD response (PMN infiltration) H. pylori population gastric cancer of gastric mucosa) chronic inflammatory response (mononuclear proinflammatory cells) of gastric mucosa remote effect cytokines Speculated link to endocrine may spread to involve disorders: extraintestinal tissues linked to digestive thyroid diseases and organs conditions and diseases diabetes mellitus dyslipidemia obesity osteoporosis primary hyperparathyrodism Papamichael et al. 2009. Helicobacter pylori infections and 54 endocrine disorders: is there a link?. World J Gastroenterol.  Dr Jorge Garcia-Lara H. pylori and diabetes H. pylori prevalence in patients with Diabetes type I or II For type II presence correlated with Dyspeptic symptoms Why? Gastritis ❑ Reduced gastric motility Esophagitis and peptic ulcer ❑ Reduced peristaltic activity Cardiovascular autonomic ❑ Changes in gastric mucosa neuropathy after non-enzymatic glycosylation processes Age (particularly middle age) ❑ Impaired non-specific immunity Gender (particularly female) in diabetic patients BMI Blood pressure Fasting glucose HbA levels In other studies, the total opposite Papamichael et al. 2009. Helicobacter pylori infections and endocrine disorders: is there a link?. World J Gastroenterol. 55  Dr Jorge Garcia-Lara … it all depends on what studies … H. pylori, and in particular CagA+, association with: nephropathy retinopathy microangiopathy coronary heart disease thromboocclusive cerebral disease 56  Dr Jorge Garcia-Lara 6x 57  Dr Jorge Garcia-Lara Diabetes and the immune system Casqueiro et al. 2016. Infections in patients with diabetes mellitus: a review. Indian J Endocrinol Metabol. S27 58  Dr Jorge Garcia-Lara Diabetes and the immune system Direct effects IL-10 IL-1 TNFa IFNg IL-6. hyperglycemia impared complement system Ig glycation Hb glycation glycation status NADP. exhaustion co- morbidities - G6PD Casqueiro et al. 2016. Infections in patients with diabetes mellitus: a review. Indian J Endocrinol Metabol. S27 59  Dr Jorge Garcia-Lara Diabetes directly affects the immune system impairing its function thus lowering its ability to protect against pathogens infectious agents that would be kept at bay in a healthy individual with an opportunistic infection, become aggressive pathogens difficult to control high incidence of superficial & deep-seated soft tissue infection diabetic foot ulcers affect mill. worldwide - w/ complex patient care and requiring the contribution of multi-professional collaboration 85% of the lower-limb amputations (specially with polymicrobial) 60  Dr Jorge Garcia-Lara cuts and abrasions lead to ulceration are greatly influenced by: the immunopathy (e.g., neutrophils remain at the inflammation site) the vasculopathy (ROS produced by cellular effectors of the immune system damage tissue regeneration precursors like lipids, …) it all may lead to: unresolved infections that result in turn in chronic inflammation and tissue destruction which interferes with/impairs the process of wound healing 61  Dr Jorge Garcia-Lara typical infectious agents in diabetic patients correspond to members of the microbiome - capitalize on barrier breakage and a compromised immune system wound infections in diabetic patients are commonly polymicrobial (as many as 50% of them) polymicrobial = careful testing & interpretation, i.e., microbiota cross contamination often with multidrug resistant (MDR) microorganisms common infectious agents: gram-negative rods like Pseudomonas aeruginosa, and Escherichia coli gram-positive cocci Streptococcus pyogenes, Staphylococcus aureus, Enterococcus spp (or E. faecium/E. faecalis), and Staphylococcus epidermidis (CoNS) fungi: Aspergillus (typical component of the feet mycoflora - characterised (amongst other features) by hyphal type growth and the distinctive formation of spores), and Candida 62 Candida AMR resistance is a problem, Dr Jorge Garcia-Lara and it is becoming a particular problem amongst the non-albicans Candida Candida glabrata (a non-albicans): resistant to both azoles and echinocandins (micafungin) “interesting” – C. glabrata tend to mutate to MDR phenotype in vivo in a single patient Like the Ascomycete Candida, the Zygomycetes like Mucor spp. Also display less anti-fungal susceptibility 63  Dr Jorge Garcia-Lara Management/treatment complications AMR antibiotics, e.g., flucloxacillin antifungals, e.g., for fungal deep seated infections in limbs can vary between 1 to 20% to common antifungals, like fluconazole, flucytosine and amphotericin B mono- and poly-microbial infections of the skin, including the diabetic foot, is the formation of biofilms biofilms they are more refractory to: antimicrobial treatment phagocytosis determine the need for debridement of necrotic areas determine the presence of an underlying internal abscess - needs to be drained by surgery before proceeding with antibiotic treatment allergy or intolerance to first line antibiotics (flucloxacillin, ciprofloxacin, metronidazole and vancomycin); alternatives, e.g., clindamycin or linezolid 64  Dr Jorge Garcia-Lara Therapy Pathogen Condition Therapy Primary Alternative Candida spp. Non- L-AmB; Fluconazole; neutropenic Echinocandins AmB-d; candidemia (use in moderation; Voriconazole Candida infection severe illness – the (for instance for in oesophagus fluconazoles becomes fluconazole an alternative; previous resistance, or if azole exposure; treat 14 intolerant to days after 1st negative Amphotericin or culture - invasive) echinochandin) Itraconazole (for resistant organisms); Fucytosine (plus fluconazole) Amphotericin B for CNS if refractory Neutropenic Echinocandin Fluconazole (if candidemia L-AmB no recent azole or critically ill); NICE BNF. 2016. Treatment of fungal infections. Voriconazole Low and Rotstein et al. 2011. Emerging fungal infections in immunocompromised patients. F1000 Medical Reports. 3:14. 65  Dr Jorge Garcia-Lara Therapy Pathogen Condition Therapy Primary Alternative Zygomycosis Invasive L-AmB; posaconazole AmB-d posaconazole sensitivity varies a lot across zygomycetes Mucor Rhizopus spp. spp. Low and Rotstein et al. 2011. Emerging fungal infections in immunocompromised patients. F1000 Medical Reports. 3:14. 66  Dr Jorge Garcia-Lara Mucormycosis (Zygomycosis) Most of the fungi we have discussed and which are cause of infectious disease corresponds to the Ascomycetes, with the distinctive feature of having a septated mycelium, including Candida albicans, Aspergillus fumigatus, Blastomyces dermatitidis, Histoplasma capsulatum and Coccidioides immitis However, after Candida and Aspergillus or Fusarium, the next pathogen which may appear in immunocompromised patients (including diabetic patients) are the Zygomycetes primitive aseptate micellium) like Mucor spp. or Rhizopus spp., compared to the rest mentioned above, Pneumocystis or Cryptococcus Case of mucormycosis in diabetic patient 67  Dr Jorge Garcia-Lara See REFERENCE SLIDES on: Emergent Fungal infections in the immunocompromised patient (Pathogen, condition, primary/alternative therapy) 68  Dr Jorge Garcia-Lara MICROBIOLOGY Unit: ISCM Module: UM2010 Yr. 2024-2025 by : LECTURE 4 INDEPENDENT Dr. GARCIA-LARA STUDY Bitesize 6 SLIDES School of Medicine Medicinae Baccalaureus Baccalaureaus Chirurgiae (MBBS) Physician Associate Studies (MPAS) 69  Dr Jorge Garcia-Lara Primary immunodeficiencies inherited acquired genetic mutation due to infectious disease mainly recessive mutations HIV (autosomal or X-linked) other viruses different pathogens malnutrition depending on gene induced immunosuppresion defect enhanced susceptibility to infection 70  Dr Jorge Garcia-Lara Primary immunodeficiencies Defects in phagocyte function (innate immunity deficiency) Complement deficiencies B-cell immunodeficiencies T-cell immunodeficiencies Cryptosporidium spp. oocyte 71  Dr Jorge Garcia-Lara Primary immunodeficiencies Nocardia zapadnaye Defects in phagocyte function (innate immunity deficiency) Staphylococcus aureus, Serratia marcescens, Klebsiella spp., Nocardia spp. Candida spp. and Aspergillus Complement deficiencies S. pneumoniae, S. pyogenes, S. aureus, N. meningitidis, N. gonorrhoea, H. influenzae B-cell immunodeficiencies S. pneumoniae, Streptococci spp., H. influenzae, enteroviruses and parasites (Giardia lamblia, Cryptosporidium spp.) T-cell immunodeficiencies Mycobacterium spp. Candida spp., Herpeviridae, enteroviruses, P. jirovecii 72  Dr Jorge Garcia-Lara Primary immunodeficiencies Defects in phagocyte function (innate immunity deficiency) LAD1 : Leukocyte adhesion deficiencies Type 1 CGD : Chronic granulomatous disease Complement deficiencies B-cell immunodeficiencies XLA : X-linked agammaglobulinemia XLHM : X-linked hyper-IgM Syndrome T-cell immunodeficiencies (typically combined with B dysfunctions) X-linked /or autosomal SCID : Severe combined immunodeficiency (group of disorders) WAS : Walcott-Aldrich syndrome (actin cytoskeleton) XLP : X-linked lymphoproliferative disease 73  Dr Jorge Garcia-Lara Primary immunodeficiencies SCID: Dave Verner. Lived in a plastic bubble. Died before the onset of treatment, stem cell transplantation, age 12 (1984). Ideal donor a healthy sibling with matched tissue type - only 25% suitable, and even less without having SCID themselves, i.e., hence donor a part, unrelated stably match adult or umbilical cord donor – also gene therapy. Dave Verner Medicinae Baccalaureus Baccalaureaus Chirurgiae (MBBS) 74 Physician Associate Studies (MPAS)  Dr Jorge Garcia-Lara Primary immunodeficiencies Defects in phagocyte function (innate immunity deficiency) severe infections by common pathogens granuloma skin and oral/anal mucosal infections Complement deficiencies rheumathoid disorders, lupus, scleroderma B-cell immunodeficiencies recurrent respiratory tract infections chronic gastrointestinal infections T-cell immunodeficiencies (typically combined with B dysfunctions) failure to thrive oral thrush 75  Dr Jorge Garcia-Lara Primary immunodeficiencies Defects in phagocyte function (innate immunity deficiency) LAD1 : Leukocyte adhesion deficiencies Type 1 (CD18 mutation; blocks phagocyte migration and inhibited bacterial uptake and degradation) CGD : Chronic granulomatous disease mutations in NADPH oxidase, G6PD (X-linked), myeloperoxidase, glutathione reductase and synthetase no hydrogen peroxide or hipochlorite Complement deficiencies B-cell immunodeficiencies T-cell immunodeficiencies (typically combined with B dysfunctions) 76  Dr Jorge Garcia-Lara Chronic granulomatous disease (CGD) hereditary disease where neutrophil granulocytes are unable to destroy ingested pathogens. it leads to the formation of granulomata in many organs (granulomatosis) (rare disease) 1 on 250,000 live births – US (similar UK); 1/450,000 – Sweden 1,000,000 people (US) 77  Dr Jorge Garcia-Lara Chronic granulomatous disease children with CGD are usually healthy at birth typically infections with Staphylococcus aureus, Burkholderia cepacia complex, Serratia marcescens, Nocardia sp.. and Aspergillus common CGD infection in infancy is a skin (impetigo, cellulitis) or bone (osteomyelitis; typically Serratia marcescens) infection any infant with an infection with any of the organisms previously should be tested for CGD pneumonia with Aspergillus (typically fungal pneumonias do not cause fever); with the bacterial pathogens typically with fever – Nocardia – very high fever and aggressive lung destruction liver abscesses typically with S. aureus 40-50% of patients develop gastrointestinal issues 78  Dr Jorge Garcia-Lara Case Study ACGD 12-year -ol d boy was admi t t ed t o t h e h ospi t al because of f ever , Mohsen Esfandbod, M.D. chills, sweats, productive cough, nausea, and vomiting. He had been subject Maryam Kabootari, M.D. to recurrent pneumonias since the age of 5 years. On physical examination, Tehran University of Medical Sciences he was febrile, tachycardic, and tachypneic; diffuse rhonchi were heard in both Tehran, Iran lungs. The patient also had finger clubbing, splenomegaly, and massive lymphade- [email protected] A 12-year -ol d boy was admi t t ed t o t h e h ospi t al because of f ever , Mohs nopathy in the cervical, axillary, and preauricular areas (Panel A) and the epitroch- lear and inguinal areas (Panel B) of his body. Blood cultures grew Staphylococcus chills, sweats, productive cough, nausea, and vomiting. He had been subject Marya aureus. A chest radiograph (Panel C) and computed tomography of the chest revealed to recurrent pneumonias since the age of 5 years. On physical examination, multiple bilateral abscesses in both lungs. The results of a nitroblue tetrazolium reduction test and immunoblotting suggested a diagnosis of chronic granuloma- Tehran he was febrile, tachycardic, and tachypneic; diffuse rhonchi were heard in both tous disease, which is characterized by recurrent life-threatening bacterial and fungal Tehran, infections and granuloma formation. Most patients receive a diagnosis before lungs. The patient also had f inger clubbing, splenomegaly, and massive lymphade- reaching 5 years of age. This patient was treated with trimethoprim–sulfamethox- sfandbo azole, levof loxacin, and voriconazole, with nearly complete resolution of symptoms. nopathy in the cervical, axillary, and preauricular areas (Panel A) and the epitroch- Lifelong prophylaxis with trimethoprim–sulfamethoxazole and itraconazole was lear and inguinal areas (Panel B) of his body. Blood cultures grew Staphylococcus recommended. DOI: 10.1056/NEJMicm1106350 aureus. A chest radiograph (Panel C) and computed tomography of the chest revealed Copyright © 2012 Massachusetts Medical Society. multiple bilateral abscesses in both lungs. The results of a nitroblue tetrazolium reduction test and immunoblotting suggested a diagnosis of chronic granuloma- tous disease, which is characterized by recurrent life-threatening bacterial and fungal infections and granuloma formation. Most patients receive a diagnosis before reaching 5 years of age. This patient was treated with trimethoprim–sulfamethox- azole, levof loxacin, and voriconazole, with nearly complete resolution of symptoms. Lifelong prophylaxis with trimethoprim–sulfamethoxazole and itraconazole was recommended. n en gl j med 367;8 n ejm.or g august 23, 2012 753 DOI: 10.1056/ NEJMicm1106350 The New England Journal of Medicine Downloaded from nejm.org on November 12, 2017. For personal use only. No other uses without permission. Copyright © 2012 Massachusetts Medical Society. Copyright © 2012 Massachusetts Medical Society. All rights reserved. 79  Dr Jorge Garcia-Lara Case Study CGD i mag es i n cl i n i cal med i ci n e Chronic Granulomatous Disease A B C The n ew en g l an d j o u r n al of me d i c i n e i mag es i n cl i n i cal med i ci n e Chronic Granulomatous Disease A B C A 12-year -ol d boy was admi t t ed t o t h e h ospi t al because of f ever , Mohsen Esfandbod, M.D. chills, sweats, productive cough, nausea, and vomiting. He had been subject Maryam Kabootari, M.D. to recurrent pneumonias since the age of 5 years. On physical examination, Tehran University of Medical Sciences he was febrile, tachycardic, and tachypneic; diffuse rhonchi were heard in both Tehran, Iran A 12-year also lungs. The patient -ol d boy hadwas admi t clubbing, f inger t ed t o t h e hsplenomegaly, ospi t al because ofandf ever , Mohsen massive Esfandbod, [email protected] lymphade- chills, sweats, productive cough, nausea, and vomiting. He had been subject Maryam Kabootari, M.D. School of Medicine nopathy in the to cervical, recurrent axillary, pneumonias and since thepreauricular Medicinae Baccalaureus Baccalaureaus Chirurgiae (MBBS)age of 5 years. On areas (Panel physical A) examination, and the epitroch- 80 Tehran University of Medical Sciences lear and heinguinal was febrile, areas (Panel tachycardic, Physician Associate Studies (MPAS) B) of and tachypneic;his body. diffuse Blood rhonchi werecultures grew heard in both Staphylococcus Tehran, Iran lungs. The patient also had finger clubbing, splenomegaly, and massive lymphade- [email protected]  Dr Jorge Garcia-Lara School of Medicine Questions? [email protected] @GarciaLaraClan #UCLanMicrobiology 81  Dr Jorge Garcia-Lara Diabetes increases risk of infection Candida pyelonephritis E. coli Enterobacter Proteus Klebsiella Candida Streptococcus E. coli Proteus H. pylori Candida Salmonella enteritidis Campylobacter spp. Hepatitis C & B Human Enterovirus A & B Coxsackie B Echoviruses S. aureus S. epidermidis Staphylococci GAS Pseudomonas aeruginosa 82