Outbreak of Pseudomonas aeruginosa on a neonatal intensive care unit: Lessons from a Qatari setting

Abstract

Background

Pseudomonas aeruginosa is a major cause of morbidity and mortality in neonatal intensive care units (NICUs). Robust infection prevention and control is key to reducing risk.

Aims

We describe lessons learnt from an NICU outbreak of P.aeruginosa in the main maternity hospital in the country.

Methods

Cases were identified from clinical samples and active screening. Clinical information was collected from the electronic patient record. Infection prevention and control (IPC) practice observations were made using organisational checklists and unit observations. Microbiological testing was by conventional microbiological methods. Statistical analyses were performed using R program. Associations were assessed using the Mann–Whitney U or Fisher exact test. Isolates were typed by pulsed field gel electrophoresis; gel was analysed in Bionumerics software from Applied Maths, Belgium.

Results

Five cases were identified – one was excluded as maternal acquisition. Typing showed a polyclonal outbreak. Widespread contamination of tap outlets of handwashing sinks in clinical areas was found. Main contributing factors were extensive misuse of hand wash sinks for waste disposal, improper sink cleaning, poor hand hygiene compliance and inadequate environmental cleaning.

Discussion

Successful management required a multi-disciplinary approach. All potential water sources and moist environments within and outside the unit were investigated. Interventions successfully addressed the main contributing factors, supported by good communication and robust auditing. With a diverse workforce, the challenge was to ensure housekeeping staff understood handwash sink cleaning procedures; existing training programmes were delivered in multiple languages tailored to the workforce.

Background

Pseudomonas aeruginosa is a major cause of morbidity and mortality in neonatal intensive care units (NICUs) worldwide. It is a Gram-negative bacillus, commonly found in the environment, and capable of causing severe infection through a number of virulence mechanisms such as secreted toxins, quorum sensing and biofilm formation (Reynolds and Kollef, 2021). We describe a P.aeruginosa outbreak on the Tiny Baby Unit (TBU). P.aeruginosa infections on the NICU were uncommon prior to the outbreak, averaging 2 cases a month across the entire NICU. This paper highlights lessons learnt in our healthcare setting, which employs a diverse workforce of locals and expatriates delivering high quality neonatal care.

Setting

The TBU is part of the biggest tertiary level NICU in the country. It is housed in a new, modern facility. The NICU covers two floors. The TBU was located on the west side of 4 South. The unit has babies born at less than 28 weeks gestation and/or having a birth weight of less than 1000 g. Babies have 1:1 nursing care. Staffing levels were adequate over the outbreak period.

The unit has a well-established infection control programmme focussing on 5 moments of hand hygiene, standard and transmission-based precautions, appropriate use of personal protective equipment, environmental cleaning, aseptic technique and care bundles for central venous catheters, ventilators and urinary catheters, with regular audits to monitor compliance. In the 3 months prior to the outbreak, observation audits showed a downward trend in hand hygiene (as low as 87%) and environmental cleaning (as low as 60%) compliance on some occasions.

The hospital water distribution system is designed to Health Technical Memorandum (HTM) 04-01 (England, 2021). All handwashing sinks have sensor taps with integral thermostatic valves and aerators: taps are positioned to minimise splash back from the drain. The hospital has a Water Safety Group that oversees a water testing programme, which includes random monthly sampling of tap water in clinical areas and annual testing by culture for legionella and P.aeruginosa. There had been no isolation of P.aeruginosa from any water samples prior to this outbreak.

Methods

Case definition

All babies admitted for 48 h or more in the TBU who tested positive for P.aeruginosa from any sample, irrespective of whether they had infection or colonisation (Bicking Kinsey et al., 2017).

Cases were identified from clinical samples and active screening of all TBU babies. Clinical information was collected from the hospital’s electronic patient record.

Infection prevention and control practice was audited using organisation checklists. Audits were carried out both openly and through the use of secret auditors to compare practice. This was supplemented by observations by the IPC team during frequent unit rounds.

Statistical methods

A retrospective case-control study was undertaken to identify significant risk factors for acquisition, including from the published literature (Bicking Kinsey et al., 2017; Jefferies et al., 2012). The study was undertaken prior to the typing results becoming available. All statistical analyses were performed using R program. Clinicopathological information was presented and summarised. Length of stay was presented as median and range. Categorical data such as age of gestation, birth weight, ventilation and medication type were expressed as frequencies and percentages. Association between P.aeruginosa groups and birth weight group was assessed using the Mann–Whitney U test, while the association with the other clinicopathological data were assessed using Fisher exact test.

Laboratory methods

Microbiology results were obtained from the laboratory’s information management system (LIMS). A retrospective review of the LIMS was also undertaken to identify babies from whom P.aeruginosa was isolated since the beginning of 2019 to determine if they had any epidemiological links to the TBU. Microbiology culture results of the mothers during pregnancy were also reviewed. Active laboratory surveillance for new cases was undertaken over the 12 months following termination of the outbreak.

Screening samples included rectal, nose, groin, ear and umbilical swabs and endotracheal secretions. Swabs were plated onto MacConkey agar and incubated at 37°C for 24–48 h. Endotracheal secretions were plated onto blood, chocolate and MacConkey agars as per the laboratory’s standard operating procedure for lower respiratory samples and incubated at 37°C for 18–24 h. Oxidase positive colonies were identified by the BD Phoenix™ Automated Microbiology System (Beckton-Dickinson).

A total of 90 environmental samples were cultured:

• • Swabs from tap outlets, aerators and drains of all TBU hand washing sinks

• • Tap water samples from all TBU handwashing sinks, 4South milk preparation and incubator cleaning rooms, sinks near Bed 6 and Bed 11 in 4North NICU (where cases 1 and 4 were detected) and random samples from other NICU sinks. Pre-flush samples were taken initially, and where positive, repeat pre- and post-flush samples were collected.

• • Random samples from sterile water used for irrigation bottles and humidifiers.

• • Random swabs from TBU medical equipment including incubators, ventilators, monitors

• • Random environmental swabs from TBU rooms

• • Swab and water sample from the outlet of the water plant in the centralised pharmacy compounding area used for the preparation of oral medications such as caffeine for the TBU

  • • Random samples from cleaning fluids used by housekeeping staff

Swabs were plated onto MacConkey agar and incubated at 37°C for 24-48 h. For samples from cleaning fluids and sterile water samples, 10 mL was inoculated into an aerobic blood culture bottle and incubated for up to 5 days in the BACT/ALERT Automated Blood Culture System (bioMérieux, Marcy L’Etoile, France). Positive bottles were sub-cultured onto MacConkey agar and incubated at 37°C for 18-24 h. Oxidase positive colonies were identified by the BD Phoenix™ Automated Microbiology System (Becton Dickinson Co., Sparks, Md.)

Water samples were cultured for P.aeruginosa at the Central Food Laboratories. They typed all clinical and environmental isolates using pulsed field gel electrophoresis (PFGE), using standard WHO-PulseNet ME guidelines. The gel was analysed in Bionumerics software from Applied Maths, Belgium. Of note, we deliberately sent 2 isolates from Case 2 (endotracheal secretions and nasal swab) to act as a form of quality control for the PFGE analysis.

Results

Cases

On 11th May 2019, P. aeruginosa was isolated from endotracheal secretions and blood culture respectively of two babies in different TBU rooms. The previous year, there had been a total of 22 P.aeruginosa isolates from all clinical samples across the entire NICU. As two cases had occurred within a span of 2 days on just the TBU, an outbreak was declared pending further investigation. An outbreak team was formed that included a microbiologist, neonatologist, infection prevention and control practitioners, NICU nursing head and charge nurses, an engineer, senior respiratory therapist and the Head of Housekeeping.

A total of 5 cases were identified. Case 1 in 4North from late April was found to have been transferred from the TBU and so was assumed to be the index case.

The layout of the TBU and the epidemiological curve are shown in Figure 1.

Figure 1.

Basic floor plan of the TBU with location of cases and epidemiologic curve. The TBU consists of seven patient rooms 3001-3003 and 3006-3009. All rooms have a single hand washing sink with sensor tap and two patient beds except room 3009 which is a single bedded isolation room. The incubator cleaning room is opposite room 3006. The milk preparation room is along the corridor behind the incubator cleaning room. The 4 North NICU is separated from 4 South NICU by a large reception area. 4 North consists of beds in an open area, with 4 separate rooms on the west side of the unit. The location of cases is shown. Rooms with P.aeruginosa in tap outlets/tap water are highlighted in blue.

One mother had vaginal colonisation with P.aeruginosa. She had a full term, normal vaginal delivery; her baby developed bacteraemia within a week of admission and had sadly died. Epidemiologically, this was considered probable maternal acquisition. Of the remaining four babies, two had pneumonia and two bacteraemia. One of the bacteraemia cases sadly died. All were low birth weight, with a gestational age of 28 weeks or less and diagnosed with respiratory distress syndrome. All were on invasive ventilation. All had peripherally inserted central venous catheters (PICC) and a peripheral line; two had umbilical catheters as well. Details are provided in Supplemental Table 1.

The retrospective case-control study (Supplemental Table 2) did not identify any statistically significant risks between babies with and without P.aeruginosa, including by gestational age, birth weight, gender, presence of central and peripheral lines, invasive versus non-invasive ventilation, receipt of oral medication or intravenous antibiotics, receipt of total parenteral nutrition, bathing with tap water and being in a room with P.aeruginosa in tap outlet/tap water.

Laboratory findings

P.aeruginosa was found in tap outlets and/or water samples from rooms 3001, 3002, 3003, 3008 and the milk preparation room on 4 South and the sink nearest to Case 1 on 4 North.

Active screening did not identify any new cases.

Laboratory surveillance over 12 months post-outbreak identified 2 further cases (a conjunctivitis and a bacteraemia); both with positive pre-flush samples from room handwash sinks.

Typing results

(Figure 2) showed two main clusters with only 69% similarity. Only two clinical isolates (HMC 50 and 51) had identical band patterns and both came from Case 2. Two environmental isolates (HMC 56 and 59) from the tap outlet and tap aerators of rooms 3001 and 3008, respectively, were identical, suggesting cross-contamination of these taps. No clinical isolates were identical to any environmental isolates. The closest association was found between the case 3 isolate and the one from the milk preparation room (92% homology), suggesting a common clonal origin possibly also including the case 2 isolate. In summary, the results were consistent with a polyclonal outbreak of infection.

Figure 2.

Dendrogram of PFGE results.

Observations and interventions

The outbreak team identified significant breaches to IPC practices including babies sponged with tap water instead of sterile water, handwash sinks used to discard clinical waste, domestic staff cleaning the basins first and then using the same cloth to wipe down the taps and/or not disinfecting the sinks or the taps, no documentation of the adequacy of cleaning and disinfection of incubators, no engineering protocol for the regular internal cleaning and disinfection of the sensor taps and no protocol for the changing of respiratory circuits, especially those that were opened.

A number of interventions were made as the investigation progressed (Supplemental Table 3). These included contact isolation precautions for all positive babies, a push to improve hand hygiene compliance, switch to sterile water for sponging, retraining of all domestic staff on proper handwash sink cleaning, additional 4 hourly tap disinfection with hypochlorite solution, education and extensive reminders to all unit staff to not use hand wash sinks for waste disposal, monitoring and documentation of incubator cleaning, enhanced environmental cleaning of clinical areas and the introduction of written protocols for engineering and respiratory therapy teams.

Positive hand wash sinks were removed from use until taps were cleaned and disinfected and pre-flush samples were negative. All taps on the unit were eventually dismantled, mechanically cleaned and disinfected by the engineering team, starting with those on clinical areas, then moving to milk preparation, medication and incubator cleaning rooms and then the rest of the ward. The frequency of cleaning was changed from quarterly to monthly.

There was extensive communication of findings and interventions to all unit and support staff including nursing, medical, respiratory therapy, pharmacy and engineering through safety huddles, morning report sessions, leadership huddles and via email alerts. The hospital’s public relations team were also kept up to date.

Frequent auditing demonstrated increasing compliance with the interventions over the course of the outbreak. When there were no further cases for 1 month, the outbreak was declared over.

The two cases in the subsequent 12 months were likely related to poor sink cleaning practices. Compliance with practice in other areas continued to remain high. Language barrier was identified as a major challenge to domestic staff training – most of their multinational workforce understood neither English nor Arabic. Further discussions were held with the hospitality leadership focused on ensuring only trained staff are assigned in the unit and that the focus is on training and materials in multiple languages.

Discussion

Most NICU P.aeruginosa outbreaks are from a common source related to the use of contaminated tap water (Jefferies et al., 2012). Outbreaks have also been attributed directly to the tap water in patient rooms (Bicking Kinsey et al., 2017). Between 9.7% and 68.1% of randomly taken tap water samples on different types of ICUs may be positive for P.aeruginosa (Trautmann et al., 2005). In our outbreak, P.aeruginosa was isolated from tap outlets and/or pre-flush water samples, suggesting contamination locally and not of the central water system.

The main contributing factors for sink/tap contamination are the tap design and position in relation to the drain, improper cleaning of handwash sinks that allows cross contamination from a bacterial source and misuse of sinks for purposes other than hand washing (England, 2021; Lowe et al., 2012; Roux et al., 2013). We discovered significant misuse of handwashing sinks by staff and visitors, including cleaning of used instruments, disposing of used milk and even mouth rinsing. We also found improper sink cleaning by domestic staff, that is, cleaning the sink first and then cleaning the taps with the same cloth. The fact that identical isolates were recovered from the tap aerators in rooms 3001 and 3008 which are on opposite sides of the TBU also supports external cross-contamination of the 2 outlets, most likely from housekeeping staff who have direct contact with all TBU taps during cleaning. The two sporadic infections post-outbreak were associated with tap outlet contamination of the room handwashing sinks and coincided with the arrival of new, poorly trained staff on the unit. In our multicultural setting with employees from all over the globe, our training for housekeeping staff had to be specifically tailored in multiple languages in order to achieve effective outcomes. Reports on the control of carbapenemase-producing bacteria outbreaks on intensive care units have shown that common measures for dealing with sink contamination have included sink removal, use of physical barriers or design modification to protect patients from sink splashes, engineering controls to mitigate bacterial dispersal and administrative controls (Kearney et al., 2021). Whilst we agree that such measures may be necessary to control some outbreaks, a strict implementation of proper cleaning and proper sink use helped achieve the same result.

A prospective study (Valentin et al., 2021) on the incidence of and risk factors for sink contamination with multi-drug resistant P.aeruginosa and Enterobacterales found that sinks disinfected daily with bleach had lower contamination rates than those disinfected with quaternary ammonium compounds and sinks with no disinfection. We believe introducing hypochlorite spray to the cleaning regimen further minimised sink contamination.

The tap design was not considered to be a contributing factor in our outbreak. Our taps aerators have a low surface to volume ratio and had been approved by the IPC team prior to installation. The position of the sensor does not create a splash back from the drain. However, we did increase the frequency of mechanical cleaning and disinfection of the taps to minimise the buildup of biofilm in view of the widespread contamination found. The role of electronic taps in the spread of water-borne pathogens is not clear cut. One study (Charron et al., 2015) found no difference in the prevalence rates of P.aeruginosa in water from manual or electronic taps except electronic taps with a more complex internal design and therefore a higher mitigating volume. This was supported by another study (Walker et al., 2014) that found the highest incidence of P.aeruginosa colonisation in complex aerator designs in sensor taps. Another report (Mayes et al., 2014) also showed that repeated simplifications to their complex sensor tap design over months during a P.aeruginosa outbreak, beginning with the removal of the aerators, significantly reduced contamination. HTM-04-01 part C (England, 2021) does not make specific recommendations regarding manual or sensor taps; where used, an aerator design with a low surface area to volume ratio is advised.

A number of risk factors have been associated with P.aeruginosa acquisition in intensive care. Factors identified in NICUs have included: multiple courses of and prolonged antimicrobial therapy (Jefferies et al., 2012), use of umbilical (Jefferies et al., 2012) and peripherally inserted central venous catheters (Bicking Kinsey et al., 2017), administration of total parenteral nutrition simultaneously with glucose/electrolyte solution (Jefferies et al., 2012), invasive ventilation (Bicking Kinsey et al., 2017), non-installation of point of use filters on tap outlets (Bicking Kinsey et al., 2017) and poor healthcare worker (HCW) hand hygiene including use of artificial nails (Jefferies et al., 2012). One study (Hoang et al., 2018) on adult intensive care units highlighted risks as: use of antibiotics inactive against P. aeruginosa, tap water contamination at the entry in the room and mechanical invasive ventilation. Another study (Venier et al., 2014) in adult ICUs found patient factors for acquisition as cumulative duration of mechanical ventilation and cumulative days of antibiotics not active against P. aeruginosa. They also found that nursing staff shortages measured as cumulative daily ward ‘nine equivalents of nursing manpower score' (NEMS) and contaminated tap water in patient’s room were also risk factors. Our case-control study was limited by a very small size and did not identify any statistically significant patient risks including for, somewhat surprisingly, sponging with tap water.

Despite staffing numbers being adequate, there was a steady deterioration in IPC practices leading up to the outbreak suggesting this area was of low priority for staff. A renewed emphasis particularly on hand hygiene through education and good communication facilitated the implementation of interventions.

Typing showed a polyclonal outbreak. Outbreaks by a single strain are often associated with an environmental water source such as water baths, milk pasteurisers, humidifying equipment for ventilators, multi-dose vials of parenteral nutrition, bottled mineral water used for multi-dose milk preparation and feeding bottles (Jefferies et al., 2012). However, genetic diversity of clinical and environmental strains found in intensive care is common (Bicking Kinsey et al., 2017). Multiple genotypes of the organism are often present in tap water and up to 50% of infection or colonisation episodes may be from strains that had been previously isolated from tap water outlets (Trautmann et al., 2006). All clinical isolates did belong to the same cluster as the isolate from the milk preparation room so a common clonal origin is possible. As typing could only be carried out on a limited number of colonies, closer associations could have been missed.

Conclusion

Successful management required a multi-disciplinary approach. All potential water sources and moist environments within and outside the unit were investigated. Interventions successfully addressed the main contributing factors, supported by good communication and robust auditing. With a diverse workforce, the challenge was to ensure housekeeping staff understood handwash cleaning procedures; existing training programmes were delivered in multiple languages tailored to the workforce.

ORCID iD

Hawabibee Mahir Petkar https://orcid.org/0009-0005-0326-3708