A 45-year-old woman has been referred to the High Dependency Unit from the Emergency department for haemodynamic monitoring following an episode of hypotension, which has responded to 3L fluid resuscitation.
She had presented with one day of worsening malaise and myalgia on a background of having just completed a six week course of intravenous flucloxacillin for osteomyelitis of her left foot administered through a peripherally inserted central line (PICC). Examination in the emergency department revealed that she was febrile (38.5oC), tachycardiac (120 bpm) and hypotensive (90/60mmHg) but otherwise was unremarkable. The PICC is still in situ.
No abnormality detected
The admitting team commences daily intravenous ceftriaxone 1gm and azithromycin 500mg with a provisional diagnosis of sepsis of unknown origin.
Please comment on the antibiotics chosen and justifications for your comments.
The rest of the viva focussed on antimicrobial prescribing.
The college clearly wanted you to criticise the choice of antibiotics as inappropriate. The agents chosen are for community acquired pneumonia.
If this was really PUO, the current Sanford gide recommendations are to use broad spectrum drugs early, (see under "Sepsis, adult") . The "non-neutropenic adult with clinical syndrome comaptible with bacterial infection" is supposed to get meropenem and vancomycin.
What antibiotic therapy would you recommend? Why?
The candidate should be able to debate the possible sources of infection here, which caould be numerous. Of these the most likely is the old line. The PICC should be mentioned at some stage.
Good gram-positive cover should be discussed.
Specifically, the candidate needs to specify doses.
The specific dose of Vancomycin is 30mg/kg
What other specific management would you recommend?
Specific to source control
- Pull the line out.
- Send it for culture.
- Resite another central line.
Specific to sepsis
- Immediately, give the antibiotics
- Immediate fluid bolus
- Endpoint of therapy is MAP >65, u/o > 0.5ml/hr, and a decreasing lactate
The PICC is removed and sent for culture.
The ED registrar is in the process of putting in a fresh IJ central line. She asks you whether you would like to get some cultures taken.
- Generally speaking, the practice of taking cultures from CVCs is discouraged by guideline-makers (eg. the American College of Physicians).
- Cultures collected during CVC insertion are more likely to yield contaminants than peripheral blood cultures (8% of the time vs. 3% of the time)
- The resulting false positive results can increase laboratory costs by 20% and antibiotic costs by 39%, not to mention the costs involved in resiting the line, and the increased risk of repeated central line cannulation.
- Almost half of the patients with coagulase-negative staphylococci in their CVC cultures end up getting antibiotics (usually vancomycin) which, apart from its expense, can't be good for the development of antibiotic resistance.
- However: There are no good quality studies to confirm that these concerns are valid; none of the available studies were blinded, and there is thus far no "gold standard" definition of bacteraemia against which they could be held.
She does not listen to you and takes CVC cultures anyway. The patient is stabilised in the ICU on a low dose of noradrenaline.
Those blood cultures come back positive for "Gram-positive Cocci".
Which among such organisms would classically represent "true" bacteraemia, and which are usually contaminants?
Audits of blood culture results have revealed a series of organisms which almost always represent a true systemic bacteraemia or fungaemia:
- Coagulase-negative staphylococci.
- Staphylococcus aureus
- Streptococcus pneumoniae
- Streptococcus pyogenes
- Streptococcus agalactiae
The organism is identified as S.epidermidis. What is the meaning of this result? How will you react?
The correct answer would include a caution to trust the culture (rather than dismissing it immediately as a contaminant).
Are you aware of any techniques which could be used to discriminate a true bacteraemia from a contaminated sample?
There are a couple:
Differential time to positivity
- When you draw a positive blood culture from the CVC, you are left guessing: is the CVC really contaminated with that organism, or did I just suck up bacteraemic blood through a nice clean CVC (and the source is elsewhere)?
- Differential time to positivity is a potential means of discriminating "true" CVC -related bacteraemia from systemic bacteraemia.
- One takes two sets of cultures: one from the central line, and another peripherally.
- Basically, if the CVC culture becomes positive earlier than the peripheral culture, the CVC is likely to be the source.
- Differential time to positivity of 120 minutes or more was associated with 81% sensitivity and 92% specificity for short term catheters. It is less specific in long-term lines.
- However, one ends up taking two sets of cultures, which is somewhat counterproductive if one's intention is to save money on laboratory fees.
Number of positive culture sets
- For true bacteraemias, multiple blood culture sets will usually grow the same organism .
- For patients with CVCs and a coagulase negative staph growing from different numbers of cultures, the positive predictive value was:
- 55% when one of one culture was positive,
- 20% when one of two cultures was positive,
- only 5% when one of three cultures was positive.
- The abovementioned multiple culture sets should be taken from different sites. For two positive culture sets, the positive predictive value was:
- 98% if both samples were obtained through the vein
- 96% if one sample was obtained through a central line
- only 50% if both samples were obtained through a catheter.
What are the risk factors for a clinically significant S.epidermidis bacteraemia?
- Anyone at risk of native valve endocarditis
- Artifical valves
- History of rheumatic heart disease
- Implated pacemaker, or any other surgical implant
- Low birth infant
- Elderly person (>65 years of age)
he patient remains febrile and noradrenaline-dependent during her Day 3 in ICU. The central line tip culture and previously collected peripheral cultures also come back positive for S.epidermidis.
How does this influence your management?
Source control clearly has not been achieved. The patient is likely bacteraemic from another source. The candidate should begin thinking about investigating the patient for other possible sources. If they do not start thinking in this fashion...
What additional investigations do you think would be valuable at this stage??
- Further cultures
- Susceptibility testing
- TTE, TOE
- Bone scan
- MRI of the left foot (progress of the osteomyelitis)
- CT of the chest and abdomen
The ICU registrar reports that he thinks he can hear a new murmur. What other clinical features would confirm the diagnosis of infective endocarditis?
An excellent review article form 2009 lists the following clinical features:
- Osler's nodes
- Janeway lesions
- Splinter haemorrhages
- Roth spots
- Focal neurological signs suggestive of embolic phenomena
- A new murmur or a worsening of an old murmur
- Arthralgia and arthritis
- Elevated ESR, CRP or rheumatoid factor
Are you aware of any criteria which might help you make this diagnosis?
These Duke criteria were proposed in 1994 on the basis of an analysis of 405 consecutive cases of infective endocarditis. In order to qualify for IE, one must have either
- two major and one minor criteria
- one major and three minor criteria
- 5 out of the 6 minor criteria
- Blood culture evidence of persisting bacteraemia:
- Typical microorganisms in 2 separate blood cultures, or
- Typical microorganisms in 2 blood cultures taken 12 hours apart, or
- Typical microorganisms in 3 out of 4 blood cultures all taken within 1 hour.
- Positive echo findings:
- Cardiac abscess
- Partial dehiscence of prosthetic valve
- Predisposing condition (eg. mechanical valve, IV drug use)
- Fever > 38.0°
- Vascular manifestations eg. Janeway lesions
- Immunologic manifestations, eg. glomerulonephritis
- Blood cultures which do not meet the Major Criteria
- Echo findings which do not meet the Major Criteria
A major limitation of this set of criteria is the fact that up to 20% of patients have "culture-negative" IE and end up being misclassified. Particularly, patients with Q-fever endocarditis would grow nothing in their cultures, and their diagnosis would be delayed. Some have used this to call for an inclusion of Q-fever serology among the major criteria.
On TOE, a 1.2cm mobile mass is visualised on the anterior mitral leaflet. The ID physician demands an urgent referral to cardiothoracic surgery.
What are the indications for urgent valve replacement in IE?
- Haemodynamic instability
- Aortic root abscess
- Ongoing embolic phenomena
What is evidence for benefit in patients who meet these criteria?
- A 1994 article reports that " surgical replacement of the infected valve led to significantly lower mortality (23%) as compared with medical therapy alone (56%)".
- IE recurrence was observed in 30% of patients after 30 days, and 69% of patients after 60 days.
- surgical management of infected valves decreases mortality largely by decreasing the risk of death from embolic phenomena. ((2012, NEJM)