Neonatal septicemia caused by a rare pathogen: Raoultella planticola - a report of four cases

Raoultella planticola(R.planticola) is an oxygen-demanding, membrane-free, powerless Gram-negative E. coli [1],including three known species of lyophilized Raoultella, ornine raoulella and earthen raoulella according to the rRNA and rpoB sequences in 200 1[2]. R.planticola is found in the natural environment such as water, soil and plants, etc. It also can exist in animals mucous membrane, but it is rarely isolated from clinical specimens. In recent years,there were some literature been reported that R.planticola caused different infections (bacteremia, pneumonia, retroperitoneal abscess,cellulitis,cholangitis and soft tissue infection) in adults and children. In 2018,the first case of Raoultella planticola septicemia suspected secondary to bilateral conjunctivitis in a infant was successfully treated with piperacillin-tarzobatam [3]. In this study,4 cases of neonatal septicaemia caused by Raoultella planticol were retrospectively reviewed from an electronic database of our hospital,so as to characterize its risk factors, clinical features and antimicrobial susceptibility. We hope our works is helpful to understand the neonatal R. planticola infections for pediatricians.

Between July 2014 and July 2019, 13,995 cases were admitted to the Neonatal Intensive Care Unit in our hospital, of which 281 cases were diagnosed as sepsis and 4 episodes of R.planticola were detected from blood culture specimens. In the same period, we did not find Raoultella planticola isolates from different clinical specimens,which included 1890 samples of other body fluids (such as sputum, cerebrospinal fluid, broncho-alveolar lavage fluid, pleural effusion, abdominal effusion, secretion or exudate, etc.) and catheter (such as PICC, tracheal catheter, thoracic drainage tube, abdominal drainage tube, etc.)culture. The clinical data on 4 cases was shown in Tables 1 and 2.

Although the survival rate of premature infants has been significantly improved in recent years, neonatal sepsis is still one of the main causes of neonatal death, especially for premature infants with small gestational age and low birth weight [4]. The pathogen distribution of neonatal sepsis varies with age, region, and even NICU. R. planticola is a rare cause of clinical infection in children and especially in newborns, it has been recognized as an emerging threat. Early and precise identification of R.planticola infection are very important to improve the prognosis of premature infants and to control the spread of this bacteria.

In this paper, the overall rate of nosocomial infection associated with neonatal sepsis was was 0.02% (281/13995), the R.planticola infection is responsible for 1.4%(4/281) of nosocomial infection in our NICU. Demiray T et al. [5] reported that R. planticola constituted 0.40% (n = 42) of all infectious agents from more than 1000 culture samples,and the incidence of R.planticola infections were identified as high as 80.9% (34/42 )[5], especially in ICU. Furthermore,the results demonstrated that the rate of R.planticola infection was a gradual increase year by year, and even if there was no epidemic at present, it should be paid enough attention by clinicians. R.planticola generally lives in the external environment, but may also exist in the hospital environment, and cause water pollution. In 2014, Garcia-San et al. [6] reported that a batch of liquid soap for hospital use was contaminated by R.planticola, but fortunately there was no outbreak of epidemic infection.

In our cases, all infants received at least one broad-spectrum antibiotic for more than 7 days before R.planticola infection, which indicated that infants with low immunity or potential diseases were susceptible to infection. R.planticola infections in different patterns (such as sepsis, biliary tract infection, pelvic cellulitis, urinary tract infection, etc.) seemed to occur mainly in immunocompromised patients [1, 7, 8]. Chun et al. [9] retrospectively reviewed 20 R.planticola bacteremia cases with a nosocomial infection rate of 0.08%(20/26208) and found that of the 17 (85%)patients had underlying malignant conditions. In China, Li Gang et al .[10] also performed a retrospective review of the clinical distribution and drug-resistance patterns of 34 cases with R.planticola bacteremia and the majority of these patients had immunologic functions low or the flaw.

All our patients received ventilator-assisted ventilation for more than 1 week before R.planticola infection,which suggested that tracheal intubation mechanical ventilation may also be a risk factor for infection. However, no invasive peripheral venous tube and umbilical venous tube surgery in our cases were performed, it was inconsistent with some previously researches suggesting that invasive operations may provide an infection pathway [11]. The clinical manifestations of R. planticola infections are similar to other bacterial infections. In our study, 4 patients presented poor feeding,cyanosis, apnea,desaturation,tachycardia and lethargy after R. planticola bacteremia occured. Prior to R. planticola bacteremia, Case 2 had repeatedly hyperpyrexia due to Candida guilliermondii infection. As a consequence,the clinical features of neonatal sepsis by R. planticola infections lack specificity. All infants had no intracranial infection and this was consistent with the published reportes [1, 3, 9].

There were significant differences in drug resistance of R.planticola strains in 4 cases. For example, R.planticola from blood stream infections in cases 3 and 4 were sensitive to ciprofloxacin, gentamicin and cefepime,while cases 1 and 2 were resistant to them. We determined the multidrug-resistant R. planticola isolates,which were resistant to such as cefazolin,ceftetan,ampicillin/sulbactam, piperacillin,imipenem,etc. It is significantly different from the research results of li gang et al. [10], which showed that no carbapene-resistant isolates or multidrug-resistant isolates have been determined in 34 strains of R.planticola derived from sputum or tracheal secretions. According to susceptibility testing,most of R.planticola were resistant to ampicillin, cefuroxime, cefuroxime ester and piperacillin, while carbapenem and aminoglycosides compounds were still the most effective antimicrobial agents [5]. In 2019, Pacilli M et al .[12] systematically reviewed the literature about R.planticola bacteremia in children and found that R.planticola had a good sensitivity to all antibiotics except ampicillin. However,there were some data about the carbapenem-resistant isolates of R.planticola [13, 14], of which the rate of resistance to melopinan, ertaxpenem and amine peruminis is 7.1% (3/42) [5]. As more and more multidrug-resistant isolates of R.planticola were identified in different hospitals of the world,especially carbapenem-resistant R.planticola,it was presumed that these infections may be associated with the abuse of clinical antimicrobials [15]. In the future, carbapenem-resistant R.planticola may bring difficulties in diagnosis and management,physicians must pay special attention to it. The fulminant epidemics induced by drug-resistant strains are more likely to occur in neonates, especially those with underlying diseases and immature immunity. Therefore, timely detection, isolation and effective treatment is beneficial to recovery and prognosis. In our study, the overall outcome of all infants was favorable when R.planticola was treated with antibiotic. Pacilli M et al. [12] retrospectively analyzed the relevant literature indicating that no death occurred in newbrons with R.planticola infection, which may be associated to early recognition and effective therapy.

Although the infection time of the four infants were different, all the events occurred in May and June, which may be closely related to the hot and humid summer climate in our region. Koc S et al. [16] determined that the R.planticola isolated from a surface water was resistant to Penicillins and cephalosporins. Multidrug-resistant and multi-metallic resistant strains of R. planticola may also exist in the natural environment [16]. Pan Z et al .[13] found the gene New Delhi Metallo-β-lactamase-1 (blaNDM-1) in multidrug-resistant R. planticola. They think that R. planticola is a possibly underestimated pathogen that contributes to the spread of the blaNDM-1 gene. So,environmental bacteria can easily transfer drug-resistant genes to human pathogens, resulting in the emergence of clinical multi-drug resistant strains [13]. When the R.planticola infection occured, we tried an attempt to identify all possible sources of infections, including sampling and testing the drinking water, condensate pipe water, hand sanitizer, warm box cleaning water and domestic water in the ward. None of R.planticola were determined.

To conclude, R.planticola is also a potential etiologic agent of infections in NICUs, especially challenging infections caused by multidrug-resistant R.planticola strains will probably become a concern for clinicians [5].Herein,pediatricians should not only choose antibiotics according to susceptibility testing, but also timely isolate patients to prevent an outbreak of infection. To the best of our knowledge,there are few literature on neonatal R.planticola infection. Therefore,further pediatric studies will be helpful to understand the clinical characteristics of the R. planticola infections and establish adequate management .