The Perils of MSSA
Sana Faruq Bsc. MBBS, Timothy Evans MRCS and Yogita Aggarwal MRCP
We present and discuss the case of a chronic dialysis patient who developed a Methicillin Sensitive Staphylococcus Aureus (MSSA) bacteraemia secondary to a tunnelled central dialysis catheter. MSSA bacteraemias are associated with significant morbidity and a mean mortality rate of nearly 25% . The risk of MSSA infections in renal patients with a central venous catheter is six times higher than those who have an arteriovenous fistula . To reduce the risk of deep-seated infections, disseminated disease, and to prevent the relapse of infection, central catheters need to be removed and replaced when the patient is infection-free .
A 72 year old chronic dialysis patient presented with a 24-hour history of pyrexia, rigors on dialysis, poor dialysis flow rates and a 7-day history of feeling non-specifically unwell.
The patient had end-stage renal failure (ESRF) secondary to an unknown cause, and was on thrice weekly haemodialysis via a right internal jugular tunnelled line. Arteriovenous fistula formation had been cancelled on numerous occasions due to cardiac and respiratory morbidity.
He also had a history of:
Gastric carcinoma with curative sub-total gastrectomy
Ischaemic heart disease - 3 myocardial infarctions with stents in his left anterior descending and circumflex coronary arteries
Atrial fibrillation (on warfarin)
A pacemaker for symptomatic complete heart block
Poorly controlled type 2 diabetes (insulin dependent)
The patient was reviewed on the dialysis unit and no obvious source for the pyrexia was found. The dialysis catheter tunnel and exit site were noted to be clean and free of inflammation.
Blood cultures were taken from the tunnelled catheter and from peripheral veins. As the dialysis line had become problematic, with the patient feeling worse on dialysis and with no other potential sources of infection being identified, the patient was treated empirically for a line-related blood-borne infection.
Line blood cultures rapidly grew a Staphylococcus species within 12 hours of sampling. Identification of the Staphylococci as a MSSA was available for his next review on dialysis.
At the next dialysis session: 48-hours after starting antibiotics
The patient was reviewed on his next dialysis session. He had on-going generalised malaise, and swinging pyrexias despite the initiation of appropriate first-line antibiotics. He also had positive blood cultures for MSSA. A decision was made to further manage the patient’s dialysis catheter-related MSSA bacteraemia as an inpatient.
On admission, the history and examination were no different to the information gathered some days earlier.
Throughout, the patient remained haemodynamically stable. His serum lactate was within the normal range at 1.3 and his CRP had increased from a baseline of 10 to 180 at the onset of his symptoms. On admission, 48 hours later, the level had risen to 280 and the total WCC was 32 with a significant left shift on the blood film.
The patient’s ECG, CXR and MSU were within normal parameters.
Management - 4 Point ‘excellent summary article’
1. Treatment of the MSSA bacteraemia
The keys to the successful eradication of a MSSA bacteraemia are:
- the rapid initiation and escalation of appropriate antibiotic therapy,
- removal of colonised foreign bodies and
- investigating and treating associated deep-seated infections and metastatic seeding if the clinical presentation is suggestive of this.
Vancomycin if often used in the treatment of MSSA due to the ease at which it can be given at the end of dialysis, thus ensuring compliance in patients with difficult vascular access. As it is partially removed on dialysis it should be given at the end or in the last hour. A trough level of at least 10 but preferably 15-20mg/L should be obtained to prevent the emergence of resistance during therapy and to maximise therapeutic efficacy. Vancomycin is bactericidal but is less effective when there is a high inoculation of bacterial load.
β-lactam antibiotics are superior to vancomycin in the treatment of invasive MSSA bacteraemias, associated pneumonias and endocarditis.They should be first-line in these cases. They have, in comparison to vancomycin, a more rapid killing curve and a higher efficacy. As a result they are associated with lower rates of recurrence compared to lone vancomycin therapy. Furthermore, they can be used as an adjunct to vancomycin therapy.
If patients fail to respond clinically after 24-48 hours then escalation to the addition of other anti-microbial therapies such as penicillinase-resistant antibiotics like rifampicin should occur.
The duration of successful therapy has been observed as being as long as 6 weeks if there is clinical suspicion of associated metastatic infections. In non-dialysis pauci-comorbid patients, those with uncomplicated MSSA infections tend to respond better to 2 weeks of antibiotic therapy.
2. Access Replacement or Salvage in those with Precious Access
Staph. aureus (SA) produces a biofilm matrix, made of extracellular DNA, proteins, and polysaccharides, in which it incorporates itself. The biofilm adheres strongly to foreign materials and is impenetrable. Long-term antibiotics reduce the rates of bacteraemia recurrence but do not eradicate the biofilm and act to increase the likelihood of antibiotic resistance. Thus foreign bodies should be removed.
The patient had two sources of foreign body – the tunnelled dialysis line and the pacemaker wires. The latter would have been replaced (albeit with difficulty given the patient’s frailty) had the patient failed to respond to treatment. The pacemaker wires would still be likely to be colonised with a SA biofilm, but in the absence of a bacteraemia, there is no strong clinical indication to replace them.
- The tunnelled line was removed within 12 hours of admission. The delay came about due to the correction of the INR.
- Temporary dialysis lines were used for dialysis until the patient was clinically and biochemically infection-free.
- ‘In and out’ dialysis and peripheral cannulae were used until blood cultures were negative (local unit practice).
- The tunnelled line was replaced when the CRP was close to baseline, the blood cultures were negative and the patient was afebrile for more than 72-hours.
- Had the patient had precious access then line salvage would have been considered as a last resort, given that it is associated with a greater risk of SAB recurrence and deep-seated seeding.
3. Ruling out deep-seated and or metastatic infection deposits
- As the blood cultures remained positive despite more than 72 hours of antibiotic therapy, evidence for deep-seated infection and metastatic seeding was sought.
- All patients with Staph. aureus bacteraemia (SAB) are recommended to have a trans-oesophageal echocardiogram, given the high risk of endocarditis. As this patient had PPM wires, the suspicion and risk of endocarditis was higher still.
- The patient had a normal transthoracic echocardiogram (TTE).
- A trans-oesophageal echocardiogram (TOE) could not be performed safely due to the risk of gastric perforation given the sub-total gastrectomy.
- The patient also had an US abdomen, CXR, and MRI spine (he complained of acute lower back pain) which were all within normal parameters for the patient.
- He empirically received 6 weeks of antibiotics.
4. Other Aspects in the Renal Management of this Patient
- Consideration and work-up for definitive dialysis access, such as an arteriovenous fistula.
Focus and review of local infection control policies and adherence, both at the patient level and service delivery level, to ensure measures are in place to reduce the risk of further MSSA bacteraemias in this patient and others.
Progress: The patient received empirical dual-antibiotic treatment for 6 weeks as there was a clinical concern he had a complicated bacteraemia as he was ‘slow-to-respond’ to antibiotics and had a foreign body in situ in the form of pacemaker wires which could not be easily replaced, unlike the dialysis catheter.
- SAB are common in dialysis patients with lines.
- SAB is associated with high rates of death and associated morbidity.
- Consider the likelihood of deep-seated infections and metastatic spread in clinically ‘slow-to-respond’ patients.
- In the presence of a SAB, remove foreign bodies as soon as possible in order to reduce the risk of invasive infection.We have a unit policy of 24hours from blood culture confirmation.
- Cosgrove S, Sakoulas, Perencevich EN et al. Comparison of Mortality Associated with Methicillin-Resistant and Methicillin-Susceptible Staphylococcus aureus Bacteremia: A Meta-analysis. Clin Infect Dis. (2003) 36 (1): 53-59.
- Crowleya L, Wilsonb J, Guyc R, et al. UK Renal Registry 14th Annual Report: Chapter 12 Epidemiology of Staphylococcus Aureus Bacteraemia Amongst Patients Receiving Dialysis for Established Renal Failure in England in 2009 to 2011: a joint report from the Health Protection Agency and the UK Renal Registry
- EdRen. Management of Staphylococcus aureus line-associated bacteraemia
- Stefaan J. Vandecasteele SJ, Boelaert JR, De Vriese AS. Staphylococcus aureus Infections in Hemodialysis: What a Nephrologist Should Know. CJASN August 2009 vol. 4 no. 8 1388-1400