Pseudomonas aeruginosa bloodstream infection at a tertiary referral hospital for children

Pseudomonas aeruginosa (PA) is a ubiquitous Gram-negative bacterium usually found in water, soil and plants. Studies from South Africa and Ghana have shown that it causes between 4 and 6.5% of Gram-negative BSI [1‐3]. PA typically causes healthcare-associated BSI among children with chronic or malignant diseases that are associated with impaired defence mechanisms [4, 5]. Community-acquired PA bloodstream infection (PABSI) may manifest in children with other immunodeficiency states including hypogammaglobulinaemia and neutropaenia [6‐8]. Community-acquired PABSI has also been reported among previously healthy, young children without underlying medical conditions [9, 10].

The mortality of PABSI is high. In retrospective studies from Argentina and Taiwan, case-fatality rates of 30 and 35% respectively were documented [9, 11]. Risk factors for mortality in children with PABSI include septic shock, multidrug-resistant (MDR) PA isolates, admission to an intensive care unit (ICU), the presence of an underlying disease, a pulmonary source of infection, inappropriate empiric antibiotic therapy and diarrhoea as a presenting feature [11‐14].

PA is intrinsically resistant to certain commonly used beta-lactam antibiotics such as ampicillin and ceftriaxone and can acquire resistance during therapy to other antibiotics such as the carbapenems [15, 16]. This makes the selection of empiric antibiotic therapy for suspected PABSI challenging. In a study done at a Korean university hospital in 75 children with PABSI, the prevalence of MDR PA was 11.3%. In that study, the fatality rate was higher among children with PABSI caused by MDR isolates compared to those with non-MDR PA isolates, 57.1% versus 9.1% [17].

While previous studies from sub-Saharan Africa have reported on the prevalence of PA in children with BSI, there are no paediatric studies providing detailed description of PABSI in children in sub-Saharan Africa. The present study was undertaken to address this knowledge gap.

This retrospective descriptive study was conducted on laboratory confirmed PABSI in children admitted to RCWMCH between 1 January 2009 and 31 December 2017. To the best of our knowledge, this is the first study from sub-Saharan Africa describing PABSI in detail among hospitalised children. The majority of the PABSI episodes, 69/104(66.3%) were HAIs. This is consistent with previous research that showed that PA infections are mostly healthcare-associated [11, 17]. Environmental analysis suggests that PA is found in the moist areas of hospitals such as sinks and colonises respiratory equipment in Intensive Care Units (ICUs) [13], highlighting the importance of good infection prevention and control practices in preventing healthcare-associated PABSI.

In addition to hospital admission, host factors are important determinants of infection. The prevalence of underlying chronic diseases and HIV infection were significantly higher in children with IPOA in this study. In these children, impaired host defence mechanisms are likely to increase the risk of PABSI as described in previous studies [12, 19]. The CDC definition for IPOA used in the present study includes all infections in whom the corresponding isolates were cultured on the day of admission, 2 days before admission or the day after admission, irrespective of a recent hospitalisation. In the present study 20/31 (64.5%) of the PABSI episodes classified as IPOA were preceded by hospitalisation occurring within 28 days prior to the current hospitalization, suggesting that prior exposure to the hospital environment may have led to PA colonisation of the children, and effective IPC practices may have prevented some of these PABSI episodes.

PABSI can present with common childhood symptoms of a febrile illness such as respiratory distress, diarrhoea and discharging ears or with severe manifestations such as septic shock [4, 19]. In this study, respiratory distress and diarrhoea were the most common presenting symptoms.

Healthcare-associated infections were significantly more frequent in children who developed PABSI in the ICU, those with a central venous access device and/or endotracheal tube, and those who had had surgery during the current admission. Patients treated in the ICU tend to be immunocompromised, require invasive procedures and may be exposed to broad-spectrum antibiotics, and in this study those who had received intravenous broad-spectrum antibiotics such as piperacillin-tazobactam or meropenem 12 months prior to the current admission had significantly more HAI than IPOA. Implementation of appropriate infection prevention and control intervention bundles and antimicrobial stewardship must be part of ICU management to decrease the incidence of HAI caused by PA.

The overall in-hospital mortality rate of 24.2% was lower than reported in previous paediatric studies. At a single centre in China, the overall mortality rate was 52.0% over a 5-year period among 36 children, with a significant association between mortality and ineffective initial antibiotic therapy [19]. In Buenos Aires, a high overall mortality of 31.0% was reported among 100 children over a 3-year period. The deaths were associated with admission to ICU, primary bacteraemia or multidrug-resistant isolates [11]. However, in our study those who were admitted to the ICU prior to PABSI diagnosis had a lower mortality at 14 days, which may be the result of early initiation of effective empiric antibiotics, most likely meropenem which was the antibiotic commonly used as an empiric antibiotic in severely ill patients admitted to the ICU. The lower mortality in our study is likely to have been the result of the majority, (50/91(54.9%), of BSI events receiving appropriate empiric antibiotic therapy, as confirmed in the analysis of the determinants of 14-day mortality. In other studies, MDR PA and carbapenem resistance were found to be associated with mortality [20], but this was not demonstrated in our study.

At RCWMCH, the combination of piperacillin-tazobactam and amikacin is frequently used empirically when HAI is suspected. However, a carbapenem antibiotic, usually meropenem is frequently used with or without vancomycin as empiric antibiotic therapy in children with severe HAI including when septic shock is present. Of the HAI and IPOA isolates, 83.3 and 90.3% respectively, were susceptible to amikacin, whereas 58.3 and 61.3% of the HAI and IPOA isolates respectively, were susceptible to piperacillin-tazobactam. Thus, most PA isolates were susceptible to at least one antibiotic in this empiric combination.

Of 19 isolates that were resistant to meropenem, 10 remained susceptible to ceftazidime, an effective antipseudomonal antibiotic. This implies that ceftazidime can be prescribed in a subset of carbapenem-resistant PA infections, as a colistin-sparing intervention. Furthermore, the polymyxins have a narrow therapeutic window, and the major adverse effects of neurotoxicity and nephrotoxicity, makes the use of alternative agents such as ceftazidime desirable when applicable [21].

The study provides useful insights about PABSI at our institution. The most common presenting symptom was respiratory distress, whilst independent determinants of 14-day mortality were empiric antibiotic therapy to which PA isolates were not susceptible, and infections present on admission to hospital. Further research is required to determine whether the presentation of PABSI, PABSI-associated mortality and the determinants of PABSI mortality differ in other parts of sub-Saharan Africa.