Managing Staph aureus bacteraemia

Typically - blood cultures are taken out of the incubator when they flag positive. Ideally, it should be taken out as and when they flag positive but in most laboratories, it is done at designated times depending on local protocol– for example, 6 am, 11 am, 3 pm, 7 pm.

Biomedical scientists process the blood culture - they do the gram stain, set up culture plates and direct sensitivity. Gram stain result is conveyed to the microbiologist. In some laboratories, the identification could be performed directly from a positive blood culture using MALDI-ToF technology. In these cases, microbiologists become aware of the species of the bacteria within a few hours or blood culture flagging positive. This is not that common yet. For the purpose of this discussion, we will assume that microbiologists only receive the gram stain result, i.e. gram-positive cocci in clusters.

Microbiologist armed with the gram stain result (gram-positive cocci in clusters i.e. a possible Staphylococcus species) assesses the patient.

They check all the potential sources of Staph aureus infection

• skin and soft tissue infection

• bone and joint infection

• discitis (check for back pain and point tenderness)

• line or prosthesis related infection

• endocarditis (check for murmurs, and peripheral signs of endocarditis)

• abscess, including any potential intraabdominal collections (signs/symptoms- may not be obvious)

• pneumonia (Staph aureus pneumonia often follows a viral infection or it could be very severe pneumonia by PVL producing Staph aureus)

• thrombophlebitis (especially in intravenous drug abusers) & evidence of septic emboli (may need a high degree of suspicion)

Microbiologist will also, at this point check for any potential infection that could be caused by a coagulase-negative Staphylococcus (CoNS). CoNS being low virulent organisms (except S lugdunensis), typically causes infection in severely immunocompromised patients and/or prosthesis related infection.

• Is there a central line/longline/ port?

• Is there a pacemaker or other implanted device?

• Is there any other prosthesis – stent? Prosthetic joint? Graft? Mesh?

and are we suspecting an infection at any of these sites?

Now microbiologist ensures that appropriate antibiotic is in place to cover any potential pathogen.

• If we are extremely sure that it is a Staph aureus infection, we can go for a narrow-spectrum antibiotic like flucloxacillin. However, if the patient has a history of MRSA or the prevalence of MRSA in the local population is high we may have to consider vancomycin (with therapeutic drug monitoring).

• If we are not sure, for example, the primary diagnosis is pneumonia, which could be due to Staph aureus or it could be caused by other organisms like pneumococcus or H influenzae, we may consider a broader spectrum antibiotic (coamoxiclav/pip-tazobactam) until we have more information.
  If we have to cover MRSA, we may add vancomycin.

• If CoNS infection is a possibility, e.g. a potential line infection, we may consider teicoplanin or vancomycin as our drug of choice, as many CoNS are not susceptible to beta-lactam antibiotics.
  If the patient is showing signs/symptoms of sepsis, we may consider adding gram-negative cover as well (coamoxiclav/pip-taz).

• If patient is clinically well, has no signs/symptoms of infection an not on antibiotics, we may consider keeping the patient off antibiotics but with a plan to start an appropriate antibiotic if the patient becomes unwell in due course. For example, the patient presented with acute non-infective exacerbation of COPD.

At this point, microbiologist may advise to investigate if there is any obvious/highly likely source of infection is present, for example -

A new murmur and/or peripheral stigmata of endocarditis present - request a transthoracic ECHO.
A new back pain with a point tenderness - may consider requesting an MRI.
A fluctuant swelling at the injection site of an IV drug abuser - request an ultrasound scan etc.

As laboratory identification is not available yet, usually we rely on clinical information to request an investigation, if any.

Repeat blood culture: It can be considered based on the clinical situation. If CoNS infection is a possibility one or two sets of repeat blood culture may help to fetch the diagnosis. If line infection being suspected a paired blood culture (line culture & peripheral culture) or even two peripheral cultures could be useful.
If endocarditis is being suspected one/two repeat blood cultures separated in time may prove helpful. Bacteraemia in endocarditis tends to be continuous.

Although it is possible that with advancement in technology we will get the identification with one or two hours of blood culture being positive (it is actually being done in some laboratories using Maldi-ToF), still most laboratories take 8-24 hours for identification and sensitivity (could be longer).

Microbiologist, revisit the ward, to check the progress of the patient and assess the result of any investigation.

• Advice is given to the clinicians to review any potential source (see above) and direct investigation according to the clinical finding.

• Investigations: Trans-thoracic ECHO (TTE), CT scan - thorax/abdomen/pelvis, USS abdomen, CXR, doppler, MRI spine etc.

• Initiate appropriate antibiotic - based on likelihood/confirmed MSSA or MRSAMSSA - flucloxacillinMRSA - vancomycin or linezolid; alternative daptomycin. (See MRSA guideline). Antibiotics may differ based on the source of infection.

• Source control - advice the clinicians on source control. For example - drainage of abscess/empyema, line removal etc.

• Repeat blood culture - request repeat blood culture 48-96 hours after starting an appropriate antibiotic.

• Infection control - inform the infection control team. They may do a root cause analysis if it is a hospital acquired bacteraemia (post 72 hours). MSSA and MRSA are under mandatory surveillance - all the NHS trust have their targets for these bacteraemias and they try to keep the numbers below the target.

• Fill in the Enhanced Mandatory surveillance form.

• Check the progress of the investigations and suggest additional investigations if required. For example, if strongly suspecting endocarditis and TTE is negative; microbiologist may advise a cardiology review with/without trans-oesophageal ECHO (TOE).

• Check the repeat blood culture. If the repeat blood culture is negative - it is assuring that the source is likely to have been controlled, unless the investigation/ clinical examination suggests otherwise.
  If the repeat blood culture is positive, "bad news" - a source is still present. Microbiologist may advise the clinicians to investigate further. If TTE is negative or inconclusive, request TOE.

• If it is uncomplicated bacteraemia, source control achieved, repeat blood culture-negative, the patient is clinically improving, microbiologist may suggest a 2 weeks course of antibiotic, counted from the day of first negative blood culture. Although some microbiologists may prefer to give 14 days IV, most prefer to step down to oral antibiotics after an initial IV course.

• If a deep source is diagnosed, the antibiotic regimen is altered according to the diagnosis. For example, Staph aureus endocarditis may need 4- 6 weeks of antibiotics.

• Adequate source control is always important for a successful outcome.

• Renal/hepatic function, and inflammatory markers should be monitored to adjust the treatment.