Antibiotic Update 2.0, 2017

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1 Case Study 3: My patient has positive blood culture, should I start antibiotic STAT? Ooi Mong How Antibiotic Update March 2017 Sarawak General Hospital

2 A 3-day-old male infant Full term, birth weight 3.5kg, spontaneous vaginal delivery. admitted on day 3 of life for neonatal jaundice (serum bilirubin 17 mg/dl), Admission examination showed a well & active infant. Pink but jaundiced. No antibiotic was give, but a blood C&S was performed. His hyperbilirubinaemia resolved quickly with phototherapy. He remained well throughout the hospital course. On his 3 rd day of hospitalization, as you were considering discharging him home, you received a notice from the laboratory that gram positive cocci was detected from his admission blood culture.

3 What would you do next? a. Keep baby, start antibiotic (which one? IV or oral?) b. Keep baby, repeat blood C&S, start antibiotic (which one? IV or oral?) c. Keep baby, repeat blood C&S, KIV antibiotic if blood C&S remains positive d. Discharge, but with antibiotic (which one? IV as day-care or oral?) e. Discharge, ignore the result & do nothing else f. Enquire more details on: gram positive cocci, who did blood C&S?, how was it done? & decide next step thereafter

4 The role of gram stain in management of positive blood culture Gram stain distinguishes bacteria into Gram-positive or Gram negative Accurate presumptive diagnosis may be made as early as within 24H of blood culture collection based on gram stain of blood C&S isolate infection type (community vs hospital) based on clinical history optimization of initial antibiotic treatment Close communication between clinicians & laboratory is important

5 Bacilli / rods Please acknowledge the author if you are adapting and using this slide set. Gram positive cocci Gram stain In chains In clusters cocci Gram negative Bacilli / rods

6 Gram positive cocci in clusters 1. Staph aureus 2. Coagulase negative staph (CONS) Gram positive cocci in chains 1. Streptococcus 2. Enterococci Gram positive DIPLO - cocci in chain 1. Strep pneumoniae

7 Gram stain result, coupled with good history, allows early accurate presumptive diagnosis & guide treatment 3-yr-old previously healthy boy has 2 days of fever & red swollen leg [Strep pyogenes] 3-yr-old boy with AML who has been hospitalised for 4 weeks for chemo has 2 days of fever [Enteroccous (Strep) faecalis]

8 Pays attention to DETAILS & CLOSE COMMUNICATION with lab helps 50-yr-old male farmer with NIDDM admitted in a moribund state little info, apart from being unwell for 5 days high fever, malaise, abdominal pain & jaundice White cells 4000/ul Platelet 86000/ul blood culture: gram negative bacilli Your diagnosis? Your initial antibiotic treatment? B Pseudomallei blood stream infection (Melioidosis) Ceftazidime

9 Why do we need to know who did it & how was it done? Predictive value of positive result depends on i. source of sample [veins vs CVL] ii. number of blood culture sets [1 vs 2 sets ] taken Likelihood of contamination varies with: aseptic technique or just being opportunistic (convenient) if additional measures were taken to reduce risk of contamination

10 Blood culture contamination & its implications Contamination occurs when organisms that are not actually present in a blood sample are grown in culture Implications: confusing and frustrating to doctors, potentially harmful to patients inappropriate use of antibiotics toxicity, MDR organism, C difficile infection additional lab testing blood sampling higher laboratory & pharmacy bills longer hospital stays further risk of nosocomial infection

11 Let s come back to the case [1] The official microbiologic report was available the next day The result showed coagulase negative staphylococcus TTP: 2 days 2 hours 50 mins

12 Please acknowledge the author if you are adapting and using this slide set. Speciating CONS that grow from multiple blood C&S can help determine the likelihood of contamination i t n A c i t o i b, 0. 2 te a d p U Hall et al CMR Becker et al CMR 2014

13 Time to positivity (TTP) TTP: the time the blood culture bottle incubates before microbial activity is detected Concept: Bacterial inoculum of bacteraemic blood >> a contaminated culture a larger inoculum will grow faster than a smaller inoculum TTP reflects the bacterial load of the initial bacterial inoculum Haimi-Cohen et al PIDJ 2003 Weinstein JCM 2003

14 Using TTP to assess the likelihood of infection TTP > 22 h: 87% PPV for a contamination TTP < 15 h: 84% PPV for an infection Haimi-Cohen et al PIDJ 2003

15 Differentiating CONS Staphylococcal Bacteremia from Contamination by Use of TTP & Quantitative Blood Culture Methods TTP <16H: CFU>100, high grade bacteraemia TTP >20H: CFU<10,? contamination

16 What would you do now? A. Keep the baby, continue current antibiotic, even the isolate was reported to be resistant to current antibiotic regime B. Keep the baby, start [if not yet so] / change antibiotic; the choice would be based on C&S result C. Allow discharge, but start / change on oral antibiotic D. Allow discharge, with no antibiotic / stop [if he is on] antibiotic

17 Common clinical question: So is this isolate a pathogen or contaminant? Do we have a gold standard to help distinguish true pathogens from contaminants? NO, IT DOES NOT EXIST!

18 Interpretation of positive blood culture: A clinico-microbiological guidance 1. Identity of the blood isolate itself 2. Clinical features of infection: fever, leucocytosis & imaging 3. Proportion of positive blood C&S set versus total number of sets obtained 4. Time to positivity 5. Number of positive culture bottles within a culture set 6. Antibiogram (& biochemical profile) of the blood isolate Weinstein JCM 2003

19 Identity of the microorganism: Always or nearly always (90%) a true infection Staphylococcus aureus Streptococcus pneumoniae Streptococcus pyogenes Streptococcus agalactiae Listeria monocytogenes Cryptococcus neoformans Candida albicans Non-albicans Candida species E coli & other Enterobacteriaceae Pseudomonas aeruginosa Neisseria meningitides Neisseria gonorrhoeae Haemophilus influenzae Bacteroides fragilis group Weinstein JCM 2003

20 Identity of the microorganism: Rarely a true infection Corynebacterium species except C jeikieum Bacillus species except B. anthracis Propionibacterium acnes Micrococcus species Weinstein JCM 2003

21 Identity of the microorganism: Isolates that require clinical judgement Coagulase negative staphylococcus (10-26% true bacteraemia) Viridans group streptococci (70% true bacteraemia) Enterococcus (38% true bacteraemia) Weinstein JCM 2003

22 Proportion of positive blood C&S set vs total number of sets obtained Endocarditis or other bloodstream infections: all or majority are positive Contaminant culture: usually only positive in a single blood culture (when 2 sets are obtained) True bacteraemia: multiple culture sets will usually grow the same organism Obtaining > one set of blood C&S help in interpretation of positive results e.g. baseline blood culture contamination rate of 3% The probability of recovering the same organism in 2 culture sets from a patient, and of that organism being a contaminant = 0.03 X 0.03 = [9 in 10,000] Weinstein JCM 2003

23 Number of positive culture bottles within a culture set Clinically significant isolate may grow more often in multiple bottles within a set contaminants may more often grow in only one bottle of a set But this criteria is not clinically useful for CONS Peacock et al Lancet 1995 Weinstein JCM 2003

24 Interpretation of CONS-positive blood cultures: sample source & number matter When multiple cultures are obtained, PPV for true bacteraemia improve 2 sets of different site preferred maximize the diagnostic utility No. blood C&S set taken via CVL PPV 1 positive out of 1 set 55% 1 positive out of 2 sets 20% 1 positive out of 3 sets 5% Sample source when both sets are positive PPV Both from veins 98% 1 from CVL, 1 from vein 96% Both were from CVL 50% Tokars Clin Infect Dis 2004

25 Antibiogram & biochemical profile of the blood isolates The isolates have 1. IDENTICAL antibiogram & biochemical profile, they are PROBABLY identical (but only molecular typing provides 100% proof) they are likely true pathogens 2. DIFFERENT antibiogram & biochemical profiles (i.e. 2 differences in biochemical results and susceptibility pattern) they are likely to be contaminants Specificity is lower when non-quantitative methods is used Specificity level correlates with the number of antibiotics used to compare Mono- vs poly- micorbial Hall et al CMR 2006 Weinstein JCM 2003

26 Preventing blood culture contamination [1] 1. Skin preparation - Most common source of contamination: the patient s skin at collection site - Most common cause of contamination: inadequate skin preparation - Several options exist: Skin antiseptics Contamination rate (%) Min contact time 10% povidone-iodine min iodine-tincture min 70% isopropyl alcohol 2.50 povidone-iodine + 70% ethyl alcohol 2.46 P=0.62

27 Preventing blood culture contamination [2] 2. Blood culture bottle preparation - Disinfect the tops of the culture bottles before inoculating - Rubber stopper is clean but not sterile - Use alcohol or iodine to let it dry and followed by alcohol 3. Single vs double needle technique - Double needle [2.0%] vs single needle [3.7%], p < Drawback: needle stick injury

28 Preventing blood culture contamination [3] 4. Blood source: vascular catheter vs percutaneously - Common practice: not ideal but convenience & patient-friendly - Culture obtained from vascular catheter can be difficult to interpret Possible reasons for catheter-drawn blood cultures being positive true bacteraemia catheter colonisation catheter contamination. - Drawback: misleading result diagnostic error unnecessary interventions

29 Catheter-associated [CA] vs catheter-related [CR] Blood stream infection [BSI]: Sound the same but are they really? CA-BSI: BSI caused by organism not related to another infection when a central line has been in place >48H before collection of a blood culture CR-BSI: BSI with either (i) Please acknowledge the author if you are adapting and using this slide set. a positive catheter tip culture, or (ii) a positive blood culture drawn from central line consistent with a culture drawn simultaneously from a peripheral vein

30 Catheter-associated [CA] vs catheter-related [CR] Blood stream infection [BSI]: Sound the same but are they really? CA-BSI: BSI caused by organism not related to another infection when a central line has been in place >48H before collection of a blood culture Assume the catheter is THE DEFAULT focus if no other site is found CR-BSI: BSI with either (i) Please acknowledge the author if you are adapting and using this slide set. a positive catheter tip culture, or (ii) a positive blood culture drawn from central line consistent with a culture drawn simultaneously from a peripheral vein Definitive microbiologic proof of catheter involvement is required

31 How do I know the central line is infected (colonized)? Catheter tip culture [requires removal] Differential time to positivity [no removal] central line drawn culture became positive 120 minutes before that of peripheral site Ratio of quantitative culture 5:1 for the same organism [no removal] CA-BSI CR-BSI

32 18 months old boy - Presented with fulminant myocarditis - Intubated, arterial line, femoral line and peripheral lines - Cardiac function improved and extubated - Asymptomatic - Day 3 extubation bld C&S when femoral line was removed: E coli - Day 4 extubation bld C&S when arterial line was removed: Kleb pneumoniae

33 Summary Blood culture is an important tool for the diagnosis of blood stream infection Care should be taken to avoid contamination Systematic evaluation of positive blood culture report could help distinguish true infection from contamination & guide appropriate treatment

34 Thank You! Questions?

35 Thank You for Supporting Antibiotic Update 2.0 & SOSKIDS! 1. Digital hand-out 2. Certificate of attendance & evaluation form 3. Remove all bottles, papers etc from your seat

36 Next Course by PICU & SOSKIDS: July 8 & 9 Topics include: 1. Child development & learning 2. Hearing & speech 3. Common ENT problems 4. Childhood obesity 5. Chest problem 6. Skin problems in children 7. Food allergy Keep an eye on registration open date at SOSKIDS website!

37 Safe Journey!

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