Case Study: An elderly man with diabetes and chronic renal failure develops complications © Academy Of Infection Management 2015 (All Rights Reserved)

History A 72-year-old man was admitted to the Emergency Department from a haemodialysis centre with: Fever Confusion and obtundation (clouding of consciousness) Hypotension © Academy Of Infection Management 2015 (All Rights Reserved)

Examination in the emergency department The patient is: Awake, confused, non co-operative and disorientated He has: Poor perfusion No oedema and no jugular venous distention Clinical examination: Blood pressure (BP) 88/40 mmHg; heart rate 112/min; respiratory rate 30/min; temperature 39°C; sat O2 94% Pulmonary examination reveals normal breath sounds and no crackles © Academy Of Infection Management 2015 (All Rights Reserved)

Examination in the emergency department (cont’d) He has normal heart sounds and a 2/6 systolic murmur at the left sternal border (LSB) Abdominal examination is normal No pain on percussion of the costovertebral angle No meningeal or focal neurological signs Arterial blood gas findings: pH 7.23; PaO2 72 mmHg; PaCO2 22 mmHg; HCO3- 10 mmHg; sat O2 94% (FiO2 0.21); lactate 6 mmol/L (54 mg/dL) © Academy Of Infection Management 2015 (All Rights Reserved)

Past medical history Patient was doing well until 2 days previously when he developed a fever, anorexia and malaise; there were no respiratory or genitourinary symptoms Background: Patient was independent for daily activities Diabetes mellitus type 2 and hypertension Received haemodialysis for the past 8 years for chronic renal failure © Academy Of Infection Management 2015 (All Rights Reserved)

Past medical history (cont’d) Following thrombosis of 3 arteriovenous fistula (AVF), he had a femoral AV prosthesis inserted 8 months ago Medications: insulin, lisinopril, erythropoietin, folic acid, vitamin B; no antibiotics in the last 3 months No skin lesion and no inflammatory signs in the AV prosthesis area © Academy Of Infection Management 2015 (All Rights Reserved)

Question 1 Which of the following diagnoses would you consider probable for this patient? Systemic inflammatory response syndrome (SIRS) Sepsis Severe sepsis Septic shock © Academy Of Infection Management 2015 (All Rights Reserved)

Which of the following diagnoses would you consider probable for this patient? Systemic inflammatory response syndrome (SIRS) Sepsis Severe sepsis Septic shock © Academy Of Infection Management 2015 (All Rights Reserved) Answers from AIM meetings in 2007

Question 2 Which of the following do you think is the best therapeutic strategy? Vasopressors Fluids Fluids + antibiotics Antibiotics + vasopressors + oxygen Fluids + oxygen + antibiotics © Academy Of Infection Management 2015 (All Rights Reserved)

Which of the following do you think is the best therapeutic strategy? Vasopressors Fluids Fluids + antibiotics Antibiotics + vasopressors + oxygen Fluids + oxygen + antibiotics © Academy Of Infection Management 2015 (All Rights Reserved) Answers from AIM meetings in 2007

SIRS or sepsis? Fever, tachycardia, tachypnoea, hypotension, confusion, high serum lactate levels Severe sepsis Lactate 6 mmol/L (54 mg/dL) Cryptic shock? Shock? © Academy Of Infection Management 2015 (All Rights Reserved) Depending on fluid response

Question 3 Should a central venous line be inserted? Yes No Don’t know © Academy Of Infection Management 2015 (All Rights Reserved)

Should a central venous line be inserted? Yes No Don’t know © Academy Of Infection Management 2015 (All Rights Reserved) Answers from AIM meetings in 2007

Fluid resuscitation Started immediately in a patient with sepsis and a high lactate level Goals: Mean arterial pressure (MAP) ≥65 mmHg Central venous pressure (CVP) 8–12 mmHg (non-ventilated) Diuresis rate ≥0.5 mL/kg/h Central venous O2 saturation (ScvO2) ≥70% © Academy Of Infection Management 2015 (All Rights Reserved)

Clinical case Central venous line inserted Fluids (normal saline 1500 mL; CVP 12 mmHg) Hypotension (BP 88/40 mmHg) + hyperlactacidaemia (5.6 mmol/L [50 mg/dL]) Noradrenaline (0.2 µg/kg/min) MAP ≥65 mmHg Lactate 5.4 mmol/L (49 mg/dL) ScvO2 65% Haematocrit 27% © Academy Of Infection Management 2015 (All Rights Reserved)

Question Which of the following do you think is the next therapeutic step? More fluids More noradrenalin Red blood cell transfusion Dobutamine 3 + 4 © Academy Of Infection Management 2015 (All Rights Reserved)

Which of the following do you think is the next therapeutic step? More fluids More noradrenalin Red blood cell transfusion Dobutamine 3 + 4 © Academy Of Infection Management 2015 (All Rights Reserved) Answers from AIM meetings in 2007

Fluid resuscitation: What else should be done? Haematocrit 27% Red blood cell transfusion If ScvO2 <70%, transfuse until haematocrit >30% (CVP 8–12 mmHg, MAP >65 mmHg) After one unit of blood, ScvO2 72% Inotropes If ScvO2 <70% → dobutamine (CVP 8–12 mmHg; MAP >65 mmHg and haematocrit >30%) © Academy Of Infection Management 2015 (All Rights Reserved)

Results of additional examinations Haemoglobin 6.7 mmol/L (10.8 g/dL) WBC 18 x 109/L (18 000/µL) Platelets 152 x 109/L (152 000/µL) C-reactive protein 360 mg/dL Urea 7 nmol/L (42 mg/dL) Creatinine 866 µmol/L (9.8 mg/dL) Sodium/potassium 132/4.5 mmol/L (132/4.5 mEq/L) GOT/GPT 27/32 U/L Glucose 80 mmol/L (450 mg/dL) Albumin 39 g/L (3.9 g/dL) Blood cultures; three sets Chest X-ray reveals no pleural or pulmonary changes © Academy Of Infection Management 2015 (All Rights Reserved) GOT, glutamic-oxaloacetic transaminase; GPT, glutamic pyruvic transaminase; WBC, white blood cell

Question What do you think is the most probable focus of infection? Bloodstream Urinary tract Lungs Other © Academy Of Infection Management 2015 (All Rights Reserved)

What do you think is the most probable focus of infection? Bloodstream Urinary tract Lungs Other © Academy Of Infection Management 2015 (All Rights Reserved) Answers from AIM meetings in 2007

What is the most probable focus of infection? Use of an AV prosthesis during haemodialysis is a risk factor for infection (namely to the endocardium) with or without septic embolisation © Academy Of Infection Management 2015 (All Rights Reserved)

Question Which antibiotic therapy would you choose? Ceftriaxone Levofloxacin Amoxicillin/clavulanate Antipseudomonal carbapenem Vancomycin + gentamicin Vancomycin + antipseudomonal carbapenem © Academy Of Infection Management 2015 (All Rights Reserved)

Which antibiotic therapy would you choose? Ceftriaxone Levofloxacin Amoxicillin/clavulanate Antipseudomonal carbapenem Vancomycin + gentamicin Vancomycin + antipseudomonal carbapenem © Academy Of Infection Management 2015 (All Rights Reserved) Answers from AIM meetings in 2007

What is the most probable focus of infection? Use of an AV prosthesis during haemodialysis is a risk factor for infection (namely to the endocardium) with or without septic embolisation Which antibiotic therapy to choose? Risk of infection with the following if there is a prosthesis-related infection with or without endocarditis: Staphylococcus aureus Staphylococcus epidermidis Enterococci © Academy Of Infection Management 2015 (All Rights Reserved)

Antibiotic therapy The patient was started on vancomycin plus gentamicin © Academy Of Infection Management 2015 (All Rights Reserved)

Results of further subsidiary examinations Transoesophageal echocardiogram: Mild aortic stenosis; normal ventricular function; no thrombi or vegetations Ultrasound scan of AV prosthesis: No signs of periprosthetic fluid or abscess Ultrasound scan of abdominal and renal areas: Normal liver and biliary tract; kidneys with signs of chronic nephropathy but no hydronephrosis; no intra-abdominal fluid © Academy Of Infection Management 2015 (All Rights Reserved)

Follow-up: 36 hours later Patient is admitted to the ICU Fever (39°C) Confused and disorientated Noradrenaline (3 µg/kg/min) Gas exchange deteriorates Laboratory values deteriorate: WBC count 28 x 109/L (28 000/µL); C-reactive protein 500 mg/dL; Platelets reduce to 80 x 109/L (80 000/µL) © Academy Of Infection Management 2015 (All Rights Reserved) Cardiovascular dysfunction Respiratory dysfunction Haematological dysfunction

Follow-up: 36 hours later (cont’d) A urinary catheter was fitted: 60 mL of purulent urine was collected and sent for microbiological examination Pyocystitis © Academy Of Infection Management 2015 (All Rights Reserved)

Question Should the antibiotic regimen be changed? Yes No Don’t know © Academy Of Infection Management 2015 (All Rights Reserved)

Should the antibiotic regimen be changed? Yes No Don’t know © Academy Of Infection Management 2015 (All Rights Reserved) Answers from AIM meetings in 2007

Follow-up: 36 hours later (cont’d) A urinary catheter was fitted: 60 mL of purulent urine was collected and sent for microbiological examination The antibiotic therapy was changed to vancomycin plus meropenem Pyocystitis © Academy Of Infection Management 2015 (All Rights Reserved)

Further follow-up Three days after admission Four days after admission Blood cultures: Escherichia coli susceptible to third-generation cephalosporins, ciprofloxacin and carbapenems, amoxicillin/clavulanate and piperacillin/tazobactam Four days after admission Urine cultures: E. coli susceptible to third-generation cephalosporins, ciprofloxacin, carbapenems, amoxicillin/clavulanate and piperacillin/tazobactam © Academy Of Infection Management 2015 (All Rights Reserved)

Question Do you think the antibiotic regimen should be changed now? Yes No Don’t know © Academy Of Infection Management 2015 (All Rights Reserved)

Do you think the antibiotic regimen should be changed now? Yes No Don’t know © Academy Of Infection Management 2015 (All Rights Reserved) Answers from AIM meetings in 2007

Further follow-up (cont’d) The antibiotic regimen was changed to amoxicillin/clavulanate for 14 days © Academy Of Infection Management 2015 (All Rights Reserved)

Follow-up: Six days after admission Patient is awake and co-operative He is afebrile No longer receiving noradrenaline Gas exchange is improving C-reactive protein level is decreasing Platelet count is increasing © Academy Of Infection Management 2015 (All Rights Reserved)

Additional Questions What are the key learning points for this case? Which of the AIM core principles could be applied to this case? How could the educational value of this case be improved? © Academy Of Infection Management 2015 (All Rights Reserved)

Key learning points Importance of complete, early resuscitation Treatment should be guided by clear goal variables Cover all likely pathogens Locate the source of the infection Followed by source control, if possible De-escalation – drug and duration © Academy Of Infection Management 2015 (All Rights Reserved) Pyocystitis with Escherichia coli bacteraemia in a patient with diabetes and chronic renal failure on HD through vascular prosthesis