Venous catheters are the alternative for patients who do not have an arteriovenous fistula or functioning prosthesis for renal replacement therapy with haemodialysis. Although the design of the current tunnelled catheters (TCs) has improved, they continue to present higher morbidity and mortality and complication rates than other vascular accesses.1–3 Infections are the main problem, with a high risk of bacteraemia, which determines the life expectancy of patients on renal replacement therapy.4 Prophylaxis measures for handling the catheters are crucial for preventing this type of complication. Applying an aseptic solution for TC handling is a recommended practice for decreasing the risks in patients with this type of catheter.5,6 The most common causative agent for catheter-associated bacteraemia is Staphylococcus aureus, with a high associated comorbidity. While other germs are more unusual, secondary bacteraemia with less conventional germs can also be observed.7–9 We present an unusual outbreak of Serratia marcescens (S. marcescens) bacteraemia in patients with TCs for haemodialysis in 4 hospitals in the Autonomous Community of Madrid.

The study was conducted at 4 sites where cases of S. marcescens bacteraemia were identified in patients with TCs for haemodialysis. On 17 December 2014, after identifying 2 patients with TCs with positive blood cultures for an uncommon germ (S. marcescens), prevention mechanisms were activated because of the possibility of a nosocomial outbreak. The entire haemodialysis unit, the staff, and the possible sites of infection were investigated, starting with using blood cultures to monitor the at-risk patients, those with catheters, prostheses, those using the button-hole technique. Cultures were taken from the lines, dialysis machines, and the aseptic solutions applied per protocol in the units. A retrospective, multi-centre, descriptive study was conducted of all the cases identified from the first event until the outcome was considered over. The objective was to identified the number affected, the patient characteristics, the treatment received, and the course. A case was considered any patient with S. marcescens identified by blood culture with a TC for haemodialysis, whether or not there were associated symptoms. No patients who were not on renal replacement therapy were included. The 4 sites that conducted a joint analysis along with the measures applied are shown in Table 1. The sites were independent, and the treatment regimens were personalised in each hospital. Each site had its own Nephrology and Preventive Medicine section. To establish whether it was the same strain of S. marcescens, genotyping was performed using pulsed-field gel electrophoresis: the blood cultures and the samples from the contaminated solutions had to coincide.

Statistical analysis: The results are expressed as the mean and standard deviation. The median and range are included when required by the series.

The first case confirmed by blood culture was on December 6th 2014. The outbreak was suspected on December 17th given the presence of 2 other patients with positive blood cultures for the same germ. The outbreak ended on 19 February 2015, the date of the last positive case. Once the outbreak was over, 21 total patients were identified, all with positive blood cultures for S. marcescens and using TCs. Once the first cases were confirmed in different haemodialysis units, it was reported to the heads of Preventative Medicine at each site. During this period, an epidemiological study of the potential sources of infection was conducted according to each site's protocol, including the healthcare staff, materials, and machinery. Preventative control measures were also ramped up. Lastly, 11 male and 10 female patients were affected, with a mean age of 72±10 years. The mean time on haemodialysis of the affected patients was 33±13 months (range: 3–83) and the mean time since the catheter implantation was 22±13 months. The patients did not all coincide in the shifts, dialysis site, or the staff who cared for them. The most common presentation was the onset of hypotension, general discomfort, and shivering, with no fever associated with the bacteraemia in 11 cases, during the dialysis session. Temperature over 38°C was recorded in 7 cases. Three (3) cases whose were diagnosed via positive cultures were asymptomatic. The blood cultures were extracted from the lines during the haemodialysis session, in both the symptomatic and asymptomatic patients. The distribution by site and TC location are shown in Table 1. The treatment regimen was different at the 2 sites with the most patients affected. One used a treatment with ceftazidime IV (2g) after dialysis and antibiotic lock therapy with a solution of the same antibiotic (1ml of 500mg ceftazidime in 50 cc of saline solution, with a heparin solution until completing the catheter branches) for 2 weeks (in 11 patients), after confirming sensitivity. Another site used a regimen with gentamicin IV at a dose of 1mg/kg/body weight after dialysis and antibiotic lock therapy using a solution of ciprofloxacin (3ml of antibiotic [vial 200mg/100ml]+3 cc heparin 5%) for 3 weeks, after verifying sensitivity via antibiogram. Three (3) cases were given oral quinolone given the rareness of the infection, 2 cases also received vancomycin IV (1g after dialysis), one patient received oral ciprofloxacin exclusively, and another ceftriaxone IV (2g after dialysis) along with a ceftazidime lock therapy. The attack rate in the sites with the most cases described was 36.8% (7 patients affected out of 19 with TC catheters) and 46.15% (12 S. marcescens infections in 26 patients with TCs). No patients with prostheses or using the button-hole technique presented bacteraemia and their blood culture screens were negative.

Once the risk prevention measures were taken, the potential transmission vectors were reviewed and the healthcare authorities were notified. On December 19th 2014, a report was received regarding the presence of lots of the BohmClorh healthy skin chlorhexidine 2% aqueous solution (250 cc, lots I-33, I-34, and I-35) antiseptic colonised by S. marcescens. A few weeks later, the prohibition on using this solution was expanded to the 0.05% lots. Given that these formulations are routinely applied when handling catheters in these hospitals, this contaminated chlorhexidine was deemed the source of infection. After withdrawing the compromised lots, both the alcoholic and aqueous solution, no new cases were reported. The last recorded case was in February 2015. The timeline of the cases is shown in Fig. 1. Sites 3 and 4 presented one isolated episode. At site 1, after the first notification all chlorhexidine solution lots were withdrawn; at site 2 only the 2% lots were withdrawn after the first recommendation and later the 0.05% lots. To establish whether it was the same strain of S. marcescens, genotyping was performed: the blood cultures and the chlorhexidine sample from of the withdrawn lots coincided. The course was favourable in all cases, with no recurring fever, and none of the TCs needed to be removed because of the infection. The only TC removed was scheduled, since the patient recovered residual kidney function. The positive blood culture was detected a posteriori in this case, during the general unit screening. Given the absence of symptoms and that the focal point was removed, no associated antibiotic treatment was started. No patients died due to a complication secondary to the infection.

Fig. 1.

Timeline of the Serratia marcescens outbreak cases.

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S. marcescens is a gram-negative bacilli included in the same Enterobacteriaceae family as Klebsiella, Proteus or Escherichia. It is a significant cause of nosocomial infections such as bacteraemia, pneumonia, and urinary tract infections. It commonly affects patients admitted to the ICU and in neonatal units.10–12 Nosocomial outbreaks in adults are commonly related to colonisation of the respiratory and urinary tracts. It has the ability to colonise the gastrointestinal tract, skin, and inorganic treatment vehicles, as well as to survive in disinfecting substances. Its presence in intensive care units has been described, and although there are descriptions of outbreaks more than 20 years ago in haemodialysis, finding it in dialysis units is rare.13,14 In a paper published in 1991, the colonisation of the dialysers used at that time was considered the source of the outbreak.15 Presently this possibility is very low with the current control and sterilisation methods.

Bacteraemia-associated morbidity and mortality secondary to catheter infection is high, and therefore the care measures for TCs are extreme in haemodialysis units.2,4 It is well known that the contamination rates were reduced in the equipment involved, with good training and periodic retraining; with special attention to hand washing, as different papers have made it clear.16,17 Nevertheless, despite these measures, bacteraemia occurs and accounts for one of the main causes of death in haemodialysis patients. Applying antiseptic solutions prior to handling the TCs is an accepted practice for decreasing the risks of infection.5,18 The high attack rate and the onset of cases in a short period of time at several sites at the same time suggested the presence of a common vehicle. Although all sites applied conventional prevention measures, the fact that the source of contamination was the antiseptic solution used resulted in a high infection rate. Initially, the withdrawal notice was only associated with a chlorhexidine concentration, although it was later extended to all concentrations, given the common origin. This fact is likely the one that led to the outbreak being prolonged. Although all concentrations in the haemodialysis unit were removed at site 1, at site 2 other formulations were kept, according to the recommendations from the healthcare authorities, until the definitive indication to completely withdraw all the dosage forms from the same brand.

In turn, only the patients with TCs were affected, with no bacteraemia being detected in other patients who were also potentially at risk, such as the patients with PTFE prostheses or using the button-hole technique. This makes it clear that the TC patients had a higher exposure to the contaminated solutions.

The most commonly implicated germ in TC-associated bacteraemia is Staphylococcus aureus, although bacteraemia can also be secondary to other gram-positive or gram-negative bacteria, and even of fungal origin.7 In general, for any secondary bacteraemia in catheters, its removal is indicated as the main measure.19,20 Nevertheless, in haemodialysis patients with TCs, pharmacological treatment is acceptable if no severity criteria are met in order to avoid removing the TC, given its vital condition as a vascular access.21 A situation of severe sepsis, haemodynamic instability, presence of infection elsewhere, evidence of complicated tunnel-associated infection, persistent fever for 48–72h after starting antibiotic therapy or finding infection by Pseudomonas, Candida, or other fungal infections, as well as detecting multi-resistant pathogens or resistant Staphylococcus aureus are criteria for removing a colonised TC.22 In our series, the patients did not meet the severity criteria and pharmacological treatment was used. TC maintenance is a reasonable treatment option if the bacteraemia is not accompanied by severity criteria, as proposed by some guidelines. In these conditions, attempting IV antibiotic therapy for at least 2 weeks is acceptable.23 This treatment should include, as some studies have previously demonstrated, along with systemic antibiotics (oral or IV), TC antibiotic lock therapy.21,24

It is known that the presence of a biofilm in the catheter can act as a reservoir; therefore, the treatment should include this antibiotic lock therapy.25 In our series, the treatment was established with an IV regimen and catheter lock therapy based on the antibiogram, applying two different formulations that showed similar results. Both the ceftazidime and the gentamicin were effective with gram-negative bacteria, and although there is more experience with gentamicin in dialysis, it can cause more side effects.26,27 Although the antibiotic therapy regimens are usually advised for 2 weeks of treatment, site 1 opted to lengthen it to 3 weeks given the uncertainty of the course with an atypical germ.22,24 In our series, the course was favourable, without requiring the TC to be removed and with no significant associated complications. The early treatment and practice of using lock therapy probably enabled this outcome, once the source of contamination was removed from the haemodialysis units.

The appearance of bacteraemia caused by an unconventional germ like S. marcescens should put us on alert in haemodialysis units. Colonisation in aseptic solutions is rare, but it can occur. Therefore it should be a vector to be analysed in these situations. Treatment should be as early as possible and it should include TC antibiotic lock therapy. Removing the catheter may not be necessary if no severity criteria are present. Fast action, collaboration of all the facilities, and applying screening measures are key for interrupting the spread of the outbreak and achieving a favourable course for the infections. In this situation the main risk factor was using a TC. Therefore, as long as it is possible, it would be advisable to insist on reducing the number of TCs in the dialysis units.

None.