Pantoea dispersa: Is it the Next Emerging "Monster" in our Intensive Care Units? A Case Report and Review of Literature.

Hospital-acquired infections and their consequences are the main cause of morbidity/mortality in critically ill and immunocompromised patients. It becomes interesting when an unusual and uncommon microorganism is found to be the causative agent, rather than the known commensals and opportunists. We present such a case, when a multiparous female, in post lower uterine segment cesarean section period presented with fulminant septic shock, hepatic failure, coagulopathy, and ventilator-associated pneumonitis. The organism grown in the tracheal secretions turned out to be an uncommon, unusual Gram-negative Coccobacillus by the name of Pantoea dispersa, resistant to almost all the conventional antimicrobial agents. In spite of all the efforts, the patient could not be saved. However, the case has opened up a virtual "Pandora's box" of questions. Are these microorganisms, known plant pathogens, really harmful to humans? Are they commensals or virulent opportunists? Are we once again on the way to a new "Acinetobacter," like near-epidemic? This is an attempt to try and find some insight about this presently uncommon and not well known genus of Pantoea! We have tried to trace and review the related available literature in the clinical medicine.

INTRODUCTION

The ventilated patients in intensive care units (ICUs) are prone to contracting hospital-acquired infections (HAIs). In fact, it would not be an exaggeration to say that, “sepsis due to multiresistant strains” of these microbes may actually be the main cause of morbidity/mortality in such patients.[1]

Most of the ICUs have their own fair share of these “monsters,” such as Klebsiella spp., Pseudomonas spp., and the latecomer, but now well entrenched, Acinetobacter spp. All of these are from the Gram-negative (Gm-ve) spectrum, while on the Gram-positive side are of course Staphylococci spp., inclusive of methicillin-resistant Staphylococcus aureus and Streptococci spp. As the evidence stands, most of these have developed resistance to multiples of the antimicrobials leaving aside a very few at present, like, tigecycline, colistin and polymyxin-B.[2] Such is the dire state of affairs that the available literature is being flooded with the reports of very high incidence of multidrug resistant (MDR) Acinetobacter spp.[3]

We are reporting a case of a multiparous patient who in postoperative period following lower uterine segment cesarean section (LUSCS) developed sepsis, became critically ill, was referred to our ICU, had a very protracted, downward trend, did not respond to even the “reserve” antimicrobials, and succumbed. The peculiarity of this case was the isolation of an unusual and not so common microbial organism called “Pantoea dispersa.”

CASE REPORT

A 23-year-old female patient was brought to our casualty on May 16, 2018 (CR No. 18/17499); she was 2nd para (P2L1), with a cuffed endotracheal tube in situ, being ventilated with ambu bag and oxygen supplementation, while being transferred from a private hospital about 70 km from our hospital.

The elicited relevant history was very sketchy. In the referring hospital, on April 30 (17 days before referral), after doing ultrasound examination and finding, a single fetus of 38 weeks +1 day ±2 weeks, oligohydramnios, no fetal cardiac activity, no fetal movement, anterior placenta, an emergency LUSCS had been performed for intrauterine death (IUD). Apparently on the 4th postoperative day, the patient became oliguric, drowsy, developed jaundice and high-grade fever, and had to be intubated and ventilated. For the next almost 12 days, the patient remained on ventilator and was transfused four packed blood cells and 21 fresh frozen plasmas. It was also elicited that she had 2½-year-old female baby by previous LUSCS. Apart from this, there was no significant relevant present, past, family or personal history.

On examination, she was a young moderately built female, febrile, with temperature of 38.9°C, pulse rate of 140/min, blood pressure of 130/80 mmHg, SpO2 of 99% with 5–6 L/min of oxygen-enriched bag ventilation. Icterus+, pallor+, generalized anasarca, and abdominal distention++ were noted. Auscultation of the chest showed few scattered rhonchi and crepitations, abdominal wound was apparently clean, urinary catheter was in place, draining very high colored, scanty urine (about 200 ml), and nasogastric tube in situ draining dark green-colored aspirate of about 50 ml. There was bleeding per vaginum.

The patient was transferred to the ICU, where she was started on intermittent positive pressure ventilation, with volume control and pressure support.

Immediate blood investigations revealed the following: total leukocyte count of 22,000 cu/mm, polymorphonuclear leukocytosis (84%), hemoglobin of 9.3 g/dl, Prothrombin Time of (PT) 17.4 seconds. PTI Index of 74.7, and renal function tests were normal except urea of 50 mg/dl. Liver function was very severely deranged: serum glutamic-oxaloacetic transaminase 220 (6–40) IU/L, serum glutamic pyruvic transaminase 132 (6–40) IU/L, total bilirubin 3.4 (0.1–1.2) mg/dl, conjugated 2.1 mg/dl, alkaline phosphatase 120 (25–110) IU/L, total proteins 4.5 g/L (6–8), and albumin 2.0 g/L. Viral markers were nonreactive.

Subsequently, 24 h urine for albumin showed 2+ positive.

On the 2nd ICU day, May 17, all the samples, inclusive of secretions from endotracheal tube, were sent for culture and sensitivity. The patient's general condition remained critical and support with vasopressor noradrenaline and inotropic, dopamine had to be initiated.

On May 18, i.e., on the 3rd ICU day, in view of persistent abdominal distention, fever, worsening international normalized ratio (1.69), and finding of free fluid in abdominal cavity on ultrasonographic examination, the admitting team in conjunction with surgical team carried out an exploratory laparotomy. Intraoperatively, blood and blood products were provided. The intraoperative findings were insignificant except the collection of serosanguineous fluid.

On May 20, postoperative support was continued, but the patient's condition did not improve. The persistent hepatic derangement, hypoproteinemia, persistent pyrexia (38.9°C–39.4°C), polymorphonuclear leukocytosis (ranging from 25,000 to 33,000), and derangement of coagulation were the striking findings. The samples for culture and sensitivity of endotracheal secretions, which had been collected on the May 17 (next day of admission), after 72 h of incubation and reported on May 20, showed the presence of P. dispersa, as the microorganism isolated with the sensitivity and I D report, from Vitek® 2 (bioMérieux, USA) as follows:

Resistant to all the standard antimicrobials, like, amoxicillin-clavulanic acid, piperacillin/tazobactam, all the cephalosporins; all penems (mero, imi, and erta); all aminoglycosides; fluoroquinolones such as ciprofloxacin, nalidixic acid, nitrofurantoin, and trimethoprim + sulphamethoxazole, sensitive only to tigecycline minimum inhibitory concentration (MIC) 1 and colistin with MIC of ≤0.5. Hence, immediately, injection colistimethate with loading dose of 9 MU followed by 4.5 MU/day (in view of compromised renal function) was started. In spite of this treatment, the fever was persistently present, ranging between 38.9°C and 39.4°C. On May 23, the fibrin degradation products were positive and D-Dimer was negative (>200 ng/mL). The closed tracheal suctioning was revealing blood-stained secretions initially, and later on frank blood.

In addition, other samples such as blood (from central venous line), urinary catheter tip, pericardial tap, and ascitic fluid were negative for any microorganismal growth except urine on May 31, showing, “growth of Candida spp. after 24 h of incubation.”

In spite of all the possible efforts, her condition showed downward trend. The need for vasopressors and inotropes remained unabated. There was obvious and relentless progression toward frank acute respiratory distress syndrome (ARDS), with continued ventilator support varying from volume-controlled pressure support to at the end, pressure control with large amount of positive end expiratory pressure, and even inverse ratio ventilation had to be provided to maintain bare minimum oxygen saturation levels. The renal failure required multiple dialyses. Multiple packs of red blood cells, fresh frozen plasma, total parentral nutrition, enteral nutrition, and albumin were administered by appropriate routes.

On June 3, at around 12.30 AM (18th day of ICU admission), the patient suffered cardiac arrest, but was successfully resuscitated after three cycles of cardiopulmonary cerebral resuscitation. The intensive care management was continued with added support of inotropes and vasopressors. On June 5, 6.15 a.m. (20th ICU day), she had another episode of cardiac arrest, from which could not be revived in spite of sustained efforts. Hence, she was declared dead on June 5, 2018, at 7.38 a.m.

DISCUSSION

The patient came to us with the following major problems:

In postcesarean section period, already in sepsis

The sepsis was secondary to the infection by microorganism called P. dispersa, in her lungs, which she acquired in the previous hospital (most probably after the intubation and when she was on ventilator for pretty long time), from where she was referred to us (because before her admission and since then, we have no report of the same/similar organism)

As a result and secondary to complicated obstetrics, she was already in HELLP-like syndrome, with elevated hepatic enzymes, deranged coagulation profile, presence of hemolysis, and hypoproteinemia, which never improved despite of all the appropriate and timely measures/interventions

The clinical situation complicated by anemia, coagulopathy, hypoproteinemia, hyperpyrexia, and hepato-renal syndrome-like picture culminating into acute tubular necrosis and acute renal failure, requiring multiple dialyses and gradually worsening pulmonary fields leading to ARDS and its consequences, ultimately culminating into multiorgan failure syndrome (MOFS) leading to mortality.

This generally is a common presentation of patients, especially critically ill, when they land up with HAI. The propensity for hepatic derangement associated with complicated obstetrics (IUD of the fetus) was further augmented by the presence of the microorganism P. dispersa, which colonized the lungs, precipitating ARDS-like picture. Then onward, it was a downward spiral and end result was predictable. Whatever was the primary pathology, the sepsis was induced by this unusual and uncommon microorganism, which eventually blew into a fast-progressing cascade of systemic inflammatory response syndrome and MOFS and death.

The genus Pantoea belongs to family Enterobacteriaceae. They are disparate group of yellow-pigmented, rod-shaped species of Gm-ve bacteria. It was named first as Bacillus agglomerans, which was later called as Enterobacter agglomerans. Some other names such as Bacterium herbicola, Pseudomonas herbicola, Erwinia herbicola, and Erwinia millitiae were also given.[4] However, Gavini et al. in 1989 recognized all these as being synonymous, so a genus by the name of Pantoea was created for similar kind of species.[5] Genus Pantoea has around twenty different species. Two other genera, known as Tatumella and Erwinia, have close association with Pantoea, all three clubbed together in the family Enterobacteriaceae along with other groups/genera such as Citrobacter, Cronobacter, Enterobacter, Escherichia, Klebsiella, and Salmonella.[4]

Of the species reported, some like Pantoea anthophila were isolated from the plants and plant products, while some like Pantoea agglomerans from the human tissues lacerated by the plants, while some like Pantoea conspicua and Pantoea septica from human blood and stool, respectively. Surprisingly, P. dispersa was originally found from soil or processed products. Some species may have specific predilection to insects.[4]

Till recently, Pantoea was an ambiguous occurrence. In the words of researchers, “some species are plant pathogens while some are found in humans, especially Pantoea agglomerans.[6] It is noteworthy that, on the one hand, P. agglomerans is a well-documented human pathogen,[4789] even reported to be a confirmed contaminant, isolated from consumed powdered infant formula milk in neonatal ICU ward, a first report from Iran,[10] while on the other hand, it is being used for the production of “Andrimid,” a newer, promising acetyl-CoA carboxylase inhibitor, a potent, broad-spectrum antibiotic![11]

Hence, the researchers are flummoxed by the dilemma that whether Pantoea as a genus is harmless naturally existing, plant and insect pathogen, which can play a very crucial role as an antiherbicide, in chelation and absorption of heavy metals from the soil, killing of insect pests, improving the quality of soil, a producer of a promising new antimicrobial, or an innocent commensal or virulent opportunist. This most probably was true in our patient. Because of the already mentioned co-existing factors, the microorganisms acquired higher virulence, leading to rather deterioration and death.

The point of interest here is, since 2003 onward, there have been slowly, but steadily emerging evidence about the increasing involvement of P. dispersa spp. in producing opportunistic infections, especially in compromised, elderly patients.[1213] This was followed by apparently the self-proclaimed, first report of neonatal sepsis involving this subspecies in central India.[14] In 2014, there was a reported case of P dispersa, being the cause of bacteremia via a central line, again an opportunistic invasion.[15] Surprisingly, in another report from Iraq, the majority of samples contained P. agglomerans, followed by Pantoea ananatis and Pantoea calida. Their conclusion was that these are the opportunistic, MDR microorganisms commonly causing the nosocomial infections.[16] A latest report from Nepal has again shown P. agglomerans as the cause of infection in two pediatric cases, especially in the postsurgical period.[17]

Logically, based on these observations and the emerging evidence of the increasingly reported cases related to Pantoea spp. in general, recently occurring P. dispersa can be a cause for the concern, which led the authors to dwell upon the matter more in depth. The paucity of available literature, on the matter, especially related to P. dispersa, also was one of the reasons for this review.

CONCLUSION

It appears that the various subspecies of genus Pantoea, in their natural habitat, are plant or insect pathogens; although they may also play some beneficial roles, but in some special circumstances such as puncture/lacerated wounds because of plant matter; contaminated cotton bolls/dressing material, or in the hospital settings, in intravenous fluids, as virulent opportunists; in immunosuppressed or compromised, elderly or newborn, especially premature patients can produce life-threatening HAIs. The cause of concern is the increasing emergence of spp. P. dispersa with highly virulent form, shown by already acquired MDR nature, as was the case in our patient. With such a “monster” lurking around on the horizon, more awareness, about these, is needed to be spread so that the specialized systems of diagnosis, such as API® 50CHE (bioMérieux, USA) system and Vitek® system (bioMérieux, USA) and matrix-assisted laser desorption/ionization-time of flight mass spectrometry analysis (Shimadzu, Japan), are used to reach the correct identification and culture and sensitivity analysis. Rationalization of antimicrobial therapy, either empirically or with evidence, is the need of the hour!

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.