Infections in the Elderly Jérôme Fennell, MB, MSc, PhD, FRCPath Jerome.Fennell@amnch.ie Infections in Old Age • Risk Factors of Old Age • Common Infections of Old Age – RTI: Pneumonia, Influenza, TB – Skin and Soft tissue infections • Shingles • Leg Ulcers – GIT: C. Difficile – UTI: ESBLs • Renal function and aminoglycoside and glycopeptide dosing Risk factors for Infections in the Elderly Older, weaker, more at risk • • • • More comorbidities Gradual deterioration of immune system with age May be malnourished, poor accommodation More likely to harbour resistant organisms as more likely to have been – Hospitalised – in nursing home – Exposed to multiple antibiotics Cellular Immunity in the Elderly • Altered T cell phenotype   naïve T cells;  memory T cells  Reduced T cell responses      response to TCR stimulation  T cell proliferation  expression of IL2-R  IL2 production Ginaldi et al 1999 Case History: December 1999 • 67 yr old woman • PC: cough, left sided chest pain, rigors x 24h • HPC: productive cough most mornings, but increasingly purulent recently • PMHx: MI 2 yrs ago, smoked 40/day until then On Examination: • • • • T: 40oC Pulse: 130/min, BP: 145/90 Tachypnoea PMHx: MI 2 yrs ago smoked 40/day until then • Resp exam suggestive of consolidation Tests • FBC, WCC • WCC – 22, 90% neutrophils • Sputum for • Sputum – pus cells, gram microscopy and positive diplococci culture • Blood culture • CXR • ABG CXR Gram Sputum result Sputum – pus cells, gram positive diplococci…What does this tell us? More than you think – • No epithelial cells - suggests this is a good specimen from lower RT so should provide a good result on culture • Gram positive diplococci likely to be? Sputum Gram Stain • No longer done routinely • Not sensitive or specific enough • Not recommended in IDSA CAP guidelines • Guidelines now recommend another test instead... Urinary Antigen Testing • All severe pneumonias should have urine test for – Legionella Urinary Antigen – Pneumococcal Urinary Antigen • Should also think of CXR, pulse oximetry, ABG, Treatment Pneumococcus BenzylPen unless allergic or live in area of resistance (Irish rate of resistance-?) When cause unknown, use augmentin or cefotaxime to cover Haemophilus later… IV BenPen Transferred to ICU for ventilation because of hypoxia BCs – positive for S pneumoniae x2 WCC – 35 CXR – shows increasing consolidation and pleural effusion 24 hrs later – Cardiac arrest – RIP Next day S pneumoniae sensitivity available: R- Penicillin S – Erythromycin, Ceftriaxone RTI in Elderly • Strep. Pneumoniae • Influenza Virus • Recurrence of TB • Normal causes of RTI Pneumococcus • Common cause of community acquired pneumonia • Risk increased by smoking • Often occurs as secondary pneumonia after influenza infection • More common during winter months • Can also cause ENT, bacteremia and CNS infections • Latest EARSS Resistance Rates for Ireland: – Pen Non Susceptible 16.2% – Erythromycin Resistant 14.1% – Ceftriaxone/Cefotaxime Resistance Rare Pneumonia Symptoms • • • • Fever (less common in those >75) Cough with coloured sputum Pleuritic chest pain, dyspnea Altered mental function, particularly in the elderly • Increased or decreased WBC Strep pneumoniae • RTI: Amoxicillin/Clarithromycin if sensitive • If infection severe or previous antibiotic exposure, use IV Ceftriaxone or Cefotaxime • Augmentin has no added benefit because resistance is not due to B-lactamase production but do to different Pen binding proteins • In countries where Ceftriaxone resistance occurs in significant numbers use IV Ceftriaxone and IV Vancomycin empirically Pneumococcal Pneumonia • Elderly patients often have fewer or less severe symptoms than younger patients • Many community-acquired pneumonias are perfectly treatable as outpatients by oral antibiotics • >90 polysaccharide capsular types • HPSC Guidelines: Pneumococcal Vaccines 2 types of pneumococcal vaccine: 1. Polysaccharide Pneumococcal Vaccine (PPV23) – incorporates 23 of the most common capsular types which together account for up to 90% of serious pneumococcal infections – Only suitable for use in those ≥ 2 years of age 2. A conjugate 7 valent vaccine (PCV7) containing polysaccharide antigens from the 7 most common serotypes conjugated to a protein (CRM 197) has enhanced immunogenicity compared with the polysaccharide vaccine. – immunogenic even in infancy – active against approximately 70% of isolates causing invasive disease, and against a significant number of penicillin-resistant strains. HPSC Groups Requiring Vaccination At risk categories: • Asplenia or reduced splenic dysfunction (e.g. splenectomy, sickle cell disease and coeliac syndrome) • Chronic renal disease or nephrotic syndrome • Chronic heart, lung, or liver disease, including cirrhosis • Diabetes mellitus • Complement deficiency (particularly early component deficiencies C1, C2, C3, C4) • Immunosuppressive conditions (e.g. HIV, leukaemia, lymphoma, Hodgkin’s disease) and those receiving immunosuppressive therapies • CSF leaks either congenital or complicating skull fracture or neurosurgery • Intracranial shunt • Candidate for, or recipient of, a cochlear implant • Children under 5 years of age with a history of invasive pneumococcal disease, irrespective of vaccine history. Adults >65 • All should be offered single dose of Pneumococcal Polysaccharide Vaccine (PPV23) • Adults 65 years or older should receive a second dose of PPV23 if they received vaccine more than 5 years before and were less than 65 years of age at the time of the first dose. CURB-65 Score • • • • • Confusion – new onset Urea - >7 mmol/l Respiratory rate >30 breaths/minute Blood Pressure <90/60 Age>65 Score: 0-1 – Treat as outpatient 2 – consider admission or follow closely as outpatient > 3 requires hospitalization, mortality >17% Influenza • H1N1 flu pandemic declared over by WHO • now seen as part of seasonal flu • Current seasonal flu vaccine includes a H1N1 strain • Primary Influenza A infection can present abruptly as rapidly progressive diffuse pneumonia with pulmonary haemorrhage • More severe in elderly, may develop meningoencephalitis or encephalitis Influenza • Treatment: Neuraminidase inhibitors such as oseltamivir (PO) and Zanamivir (IV) given early in severe or at risk cases • Often followed by secondary bacterial pneumonia e.g. S pneumoniae, S aureus • Vaccine less effective in elderly • Adults over 50 should have annual vaccination • Those in nursing homes and other long stay facilities should also have annual vaccination Another Case • 82 year old woman with 2 months of cough, fatigue, night sweats • Poor response to Coamoxiclav, tetracycline TB in Ireland • Common in the 1950s • Many people who were exposed/treated as children then are now presenting with TB now as their immune system wanes with age Varicella Zoster Virus • Cause of Chicken Pox and later Shingles • Extremely infectious • Can be severe and even fatal in immunocompromised • Shingles not uncommon in elderly hospital patients, can leave severe pain of post-herpetic neuralgia • Pose an infection control risk to immunocompromised, and non immune staff especially to non immune pregnant staff Not routinely recommended in Elderly Leg Ulcers • As patients age, increasing peripheral vascular disease and diabetes can predispose to venous or arterial leg ulcers • Wet • Warm • Oxygenated • Below the belt • So swabs will always grow something, often grow patients bowel flora • Treat only if infected! Case History • Anne, 74 yr old housewife • PC: Elective total hip replacement – 3/7 ago • PMHx: Hypertension, Gastric Ca 13 yrs ago • 2/7 post op catheter specimen urine showed high white cells, Mixed growth predominantly gram negative bacilli • Given Zinacef po x 5/7 Case History • 3/7 after Zinacef started, complains of diarrhoea Causes: • Infectious? – Any other patients on ward affected? • Non-infective causes? • Hospital food? • Secondary to drugs: – Antibiotic assoc diarrhoea? – Clostridium difficile? Case History Investigations? Stool Culture sent: • Culture – NAD, no Salmonella, Shigella, Campylobacter, or E coli 0157 • C diff toxin studies negative Case History What next? Repeat C diff testing: Positive Treatment? Case History • Treatment – po metronidazole 250 mgs qds for 10/7 • Diarrhoea settles – D/C home • Seen in OPD: What is C. difficile? Gram positive bacillus Clostridia = anaerobe Forms spores Spread by touch, faecal-oral route Main sources are: • asymptomatic carriers • Contaminated environment Resistance to Antibiotics No antibiotic – no selection for resistant organisms sensitive resistant Resistance to Antibiotics antibiotic – selects for resistant organisms sensitive resistant Clinical Picture • Clinical ranges from mild diarrhoea to lifethreatening colitis • Occurs 1/7 to 6/52 after antibiotic exposure • Get watery diarrhoea, lower abdominal pain, blood pr Clinical Picture • Systemic symptoms: fever, anorexia, nausea and malaise • Severely ill may have no diarrhoea due to toxic megacolon • Complications: perforation, peritonitis – high mortality Risk Factors • • • • • Age Prior antibiotic use Length of hospital stay Other severe underlying disease C diff strain Antibiotic culprits • Any – including metronidazole • Main culprits include: – Clindamycin – Cephalosporins – Quinolones e.g. Moxifloxacin, Ciprofloxacin – Broad spectrum antibiotics – e.g. Augmentin, Meropenem Pathogenesis • Disrupts normal bowel flora • Many people especially neonates are colonised but not infected. • Carriers thought to have better immune response, infected tend to have lower Ab response • Two potent cytotoxins, toxins A and B • Can have colitis without pseudomembranes Spore Formation • Spores provide a method of survival when environmental conditions are unsuitable • Protect against ethanol, phenol, formaldehyde, heat • Killed by iodine, glutaraldehyde, hydrogen peroxide, autoclaving • Stomach acid kills 99% bacteria but doesn’t affect spores Pseudomembranous Colitis • Due to Clostridium difficile toxins, rarely due to S. aureus • Symptoms: diarrhoea +/- mucus or blood, abdominal pain, tenderness, fever, dehydration, electrolyte disturbances • Dx by toxin detection or by endoscopy (risk of perforation) • Tx: Stop causative agent, give metronidazole or Vancomycin PO for 10/7 Diagnosis • Culture too slow and those that grow may not express toxins • Therefore do toxin testing by ELISA • Pseudomembranes can be seen on endoscopy • Nursing nose! • No point in testing if clinically well or still on treatment • • • • • O27 strain Increasingly common Associated with quinolone use Higher mortality Higher infectivity Treatment • Hydration, electrolytes • Contra-indicated: Antiperistaltics, e.g. imodium • Severe illness may require surgery esp if perforation or toxic megacolon suspected. • Probiotics?? Half of recurrences thought to be due to reinfection rather than relapse. Metronidazole resistance rare. TX. MUST BE PO! C difficile Treatment Guide – IDSA 2010 UTIs • Men often have some degree of prostatic obstruction • As patients age greater risk of urinary and faecal incontinence • Nursing home/Hospital/Antibiotic exposure predispose to resistant organisms • Temptation to catheterise many of these patients indefinitely, this sacrifices patient outcomes for convenience Epidemiology of Extended Spectrum BLactamases - Ireland 0 Apr May Jun Jul Aug Sep Oct Nov Dec Jan Feb Mar Apr May Jun Jul Aug Sep Oct Nov Dec Jan Feb Mar Apr May Jun Jul Aug Sep Oct Nov Dec Jan Feb Mar Apr May Jun Jul Aug Sep AMNCH – Monthly ESBL Reports Q2 2007 – Q3 2010* 45 40 35 30 25 20 15 10 5 n = 760 2007 2008 2009 2010 EARSS Ireland 02-10 – E. coli EARSS Quarterly Surveillance Reports – Quarter 1 2010, HPSC ESBL Sample Type - AMNCH Female: Male 3:2 Miscellaneous 21% Sputum 7% Blood Cultures 4% Urine 68% AMNCH ESBL Age Distribution 80 70 Average Age: Median Age: 60.1 66 60 50 40 30 20 10 0 0-9 10-19 20-29 30-39 40-49 50-59 60-69 70-79 80-89 90-99 Urinary E. coli Antimicrobial Resistance Over Time 100 90 80 70 60 Ciprofloxacin-R Amikacin-R 50 Gentamicin-R Nitrofurantoin-R 40 Trimethoprim-R 30 20 10 0 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 ESBL Resistance Rates Susceptible (%) Intermediate (%) Blood Blood Urine Blood Urine 20 (5.5) Urine Resistant (%) Amikacin 11 (78.6) 312 (86.4) 2 (14) 29 (8.0) 1 (7.1) Gentamicin 9 (60.0) 254 (70.2) 1 (7) 3 (0.8) 5 (33.3) 105 (29.0) 15 (100) 302 (82.7) Ciprofloxacin 0 (0) 62 (17.0) 0 (0) 1 (0.3) Meropenem 15 (100) - 0 (0) - 0 (0) - Trimethoprim - 68 (18.6) - 0 (0) - 297 (81.4) Nalidixic Acid - 43 (11.8) - 1 (0.3) - 319 (87.9) Nitrofurantoin - 323(88.5) - 20 (5.5) - 22 (6.0) Mortality 30 day mortality (all causes) = 9.7% Irish Data (paper in production) Survival Treatment by Class • Penicillins Useless • Cephalosporins Useless • Penicillins +B-lactamase inhibitor Unreliable • Quinolones If sensitive • Aminoglycosides If sensitive • Carbapenems Most reliable...for now Carbapenems • E.g. Meropenem, 1st line choice for treatment of serious ESBL infections • stability to all the currently recognised, frequently occurring ESBLs • extensive clinical experience • Ertapenem also useful for UTIs, home IV tx (once daily) • Excess carbapenem use will result in resistance Paterson DL and Bonomo RA. Clin Microbiol Rev 2005; 18 (4): 657-686 A glimpse of the future... Other antibiotics • Nitrofurantoin po– outpatient setting • Tigecycline IV– with caution in E coli and Klebsiella (Pseudomonas and Proteus inherently resistant) • Fosfomycin, Temocillin, Pivmecillinam • Trimethoprim, Aminoglycosides, Quinolones when susceptible Paterson DL and Bonomo RA. Clin Microbiol Rev 2005; 18 (4): 657-686 Vancomycin and Gentamicin Dosing • Vancomycin and Gentamicin are nephrotoxic and ototoxic • Important not to overdose in this age group • Elderly often have some degree of renal impairment • Assess renal function by urea and creatinine levels • If normal, treat normally but watch levels after 24 h of treatment • If levels high will have to reduce dose