Microbiology Nuts & BoltsSession 2Dr David GarnerConsultant MicrobiologistFrimley Park Hospital NHS Foundation Trust

Aims & ObjectivesTo know how to diagnose and manage life-threatening infectionsTo know how to diagnose and manage common infections To understand how to interpret basic microbiology resultsTo have a working knowledge of how antibiotics workTo understand the basics of infection control

Betty82 years oldPresents with fever & shortness of breathOn examinationTemperature 38.5 oCDecreased air-entry at the right baseB.P. 120/65How should Betty be managed?

Questions to ask yourselfWhat urgent care does she need? Does she have an infection?What is the likely source of infection?What are the likely causes of the infection?Have you got time to pursue a diagnosis or do you need to treat her now?How are you going to investigate her?When will you review her?All of the above is based on your differential diagnosis

Differential DiagnosisImmediately life-threateningCommonUncommon

Examination and investigations explore the differential diagnosis

What would be your differential diagnosis for Betty?

Differential DiagnosisImmediately life-threateningSevere sepsis CommonUrinary tract infection (UTI), community acquired pneumonia (CAP), aspiration pneumoniaUncommonInfective endocarditis

How would you investigate this differential diagnosis?

Full history and examinationBloodsFBC, CRP, U&EsBlood CulturesUrineDipstickMSU (How do you take a proper MSU?)SputumChest X-ray

BloodsWBC 15 x 109/LCRP 157U&Es Urea 17, Creat 167UrineDipstick ++ leucs, ++ nitritesMicroscopy >100 x106/L WBC, no epithelial cellsSputum

How would you manage Betty now?

How to interpret a urine result?Urine dipstickPoor PPV, Good NPVMicroscopyWhite blood cells, red blood cells, epithelial cellsCulture resultIs the organism consistent with the clinical picture?

Microscopy of urineWhite blood cells>100 x106/L definitely significant>10 x106/L significant if properly taken MSU (rare!)Red Blood CellsPoor correlation with UTI, used by urologist and renal physiciansEpithelial cellsIndicator of contact with, and therefore contamination from, the perineum

Culture: classification of bacteriaCauses of UTI usually originate in the gastrointestinal tract

Bacterial Identification: Gram-negative bacilli

Culture: how is urine processed?Day 1 Automated MicroscopyIf values not significant reported as negativeIf values significant or specific patient group cultured with direct sensitivitiesDay 2Reported with identification and sensitivitiesPatient groups always culturedCancer and haematologyPregnantUrologyChildren < 5 years old

Community Normal Flora

What happens in Hospital?

Hospital Normal Flora

Factors Affecting Normal FloraExposure to antibiotics provides a selective pressuree.g. previous antibiotics for CAPIncreased antimicrobial resistant organisms in the environmente.g. Pseudomonas in intensive care unitsEasily transmissible organisms e.g. Staphylococcus aureusImmunosuppressants e.g. steroids, chemotherapy, tracheostomy tubes etc

Back to BettyBloodsWBC 15 x 109/L, CRP 157U&Es Urea 17, Creat 167Urine>100 x106/L WBCCulture Escherichia coli CXRNormalSputum culture Respiratory Commensals OnlyWhat is the diagnosis?

Types of Urinary Tract InfectionUrethral syndromeurethral infection only (women)severe dysuria and urgencyCystitisas above with infection of the bladderheavy feeling suprapubically relieved by micturitionPyelonephritisinfection involving the kidney parenchymaloin pain, fever, +/- rigors and bacteraemiaCatheter related bacteruriaAll catheters become colonised with bacteria and do not usually require treating

Types of Urinary Tract InfectionUrethral syndromeurethral infection only (women)severe dysuria and urgencyCystitisas above with infection of the bladderheavy feeling suprapubically relieved by micturitionPyelonephritisinfection involving the kidney parenchymaloin pain, fever, +/- rigors and bacteraemiaCatheter related bacteruriaAll catheters become colonised with bacteria and do not usually require treating

Do patients need antibiotics?Some bacterial infections do not need antibiotics e.g. urethral syndrome, gastroenteritisViruses do not respond to antibacterials!However there are antivirals e.g. aciclovir, oseltamivir etcThere are many non-infection reasons for signs of infections e.g. pyuria, raised CRP, crackles in the chest etcThe presence of bacteria does not necessarily mean there is an infection!Bacteria colonise, such as upper respiratory tract, surgical wounds, ulcers

How do you choose an antibiotic?What are the common micro-organisms causing the infection?Is the antibiotic active against the common micro-organisms? Do I need a bactericidal antibiotic rather than bacteriostatic?Does the antibiotic get into the site of infection in adequate amounts?How much antibiotic do I need to give?What route do I need to use to give the antibiotic?

In realityyou look at empirical guidelines

How antibiotics work

Antibiotic resistance

Other considerationsAre there any contraindications and cautions?e.g. quinolones with myasthenia gravisIs your patient allergic to any antibiotics?e.g. b-lactam allergyWhat are the potential side effects of the antibiotic?e.g. Aminoglycosides and hearing and balance disturbanceWhat monitoring of your patient do you have to do?e.g. Trimethoprim and full blood count

BettyPresumed UTIStarted on IV Co-amoxiclav and Gentamicin

Next DayMore unwell, hypotensive and tachycardicBloodsWBC 27 x 109/L, CRP 375U&Es Urea 18, Creat 178UrineMicroscopy >100 WBC, no epithelial cellsCulture = Escherichia coli, resistant to Amoxycillin, Co-amoxiclav, Gentamicin, Trimethoprim, Ciprofloxacin, Nitrofurantoin (ESBL positive)Blood CultureGram-negative bacillusWould you do anything different for Betty now?

Discussed with Consultant MicrobiologistAdvised to change antibiotic to IV Meropenem

Day 3Much improvedBloodsWBC 19 x 109/LCRP 198U&Es Urea 12, Creat 150Blood CultureEscherichia coli, resistant to Amoxycillin, Co-amoxiclav, Gentamicin, Trimethoprim, Ciprofloxacin, Nitrofurantoin (ESBL positive)What would you do for Betty now?

Continued Meropenem as no oral alternativesHow long would you treat her for in total?

Caution: Extended Spectrum Beta-lactamaseEnzyme excreted into periplasmic space which inactivates antimicrobials by cleaving the b-lactam bond.Cause resistance to almost all b-lactams including 3rd-generation cephalosporinsAssociated with multiple antibiotic resistancesCan be chromosome, plasmid or transposon encodedCan be constitutive or inducibleIdeally patients with ESBLs should be managed in side-rooms with contact precautions

Caution: Extended Spectrum Beta-lactamaseSource: European Centre for Disease Prevention and Control Antimicrobial resistance surveillance in Europe 2011

ConclusionsUTI is usually caused by bacteria from the lower gastrointestinal tractEscherichia coliProteus mirabilisKlebsiella oxytocaAll urinary catheters become colonised, they do not usually require treatingAntibiotics are chosen to treat the likely bacteriaAll of the microbiology report is important and helps with interpretation of the resultMulti-resistant bacteria often required infection control precautions

Any Questions?