Morganella morganii: An unusual analysis of 11 cases of pediatric urinary tract infections

Abstract Background The increase in rare opportunistic microbial infections caused by Morganella morganii is alarming across the globe. It has been reported that in cases of urinary tract infections (UTIs) caused by M. morganii, however, few studies investigated children. Our study aimed to analyze the risk factors, antimicrobial susceptibility, and clinical characteristics, so as to improve the clinical diagnosis and therapy of M. morganii infection. Methods Between April 1, 2017 and April 1, 2021, 11 cases of pediatric UTIs caused by M. morganii were included in this retrospective study. Medical records were reviewed and analyzed. Results The study population included 10 males and one female between 11 months and 13 years old (mean age: 4 years 9 months). The most common comorbidity was nephrotic syndrome (72.7%, 8/11). Six patients (54.5%) were in the immunosuppressed state due to chemotherapy or immunosuppressant therapy. Ten cases defined as lower UTIs with no specific clinical manifestations had normal or slightly elevated leukocyte counts and procalcitonin (PCT) levels, and normal C‐reactive protein (CRP) levels. One child diagnosed upper UTIs accompanied with fever, high level of leukocyte counts, CRP, and PCT. The M. morganii presented 100% susceptibility to aztreonam, ertapenem, meropenem, piperacillin/tazobactam, cefepime, ceftazidime, cefotetan, ticarcillin/clavulanic acid, and cefoperazone/sulbactam. Almost all patients had good responses to third‐generation cephalosporins antibiotic therapy. Conclusion Clinical vigilance for the possibility of M. morganii in pediatric UTIs in combination with underlying disease or immunosuppression is warranted. Treatment strategies should be proposed according to the clinical condition and the antibiotic susceptibility results.


| INTRODUC TI ON
Morganella morganii is a gram-negative, rod-shaped, and facultative anaerobic bacillus, which belongs to human gut commensal microbiota. 1 It is considered as a non-negligent opportunistic pathogen that mainly causes various infections, such as sepsis, abscess, urinary tract infections (UTIs), chorioamnionitis, and cellulitis. 2 Furthermore, on rare occasions, it may cause potentially fatal systemic infection, especially in postoperative environment and nosocomial as well as in young children and patients with impaired immune system. 1 UTIs are among the most common bacterial infections in children and are associated with significant short-and long-term morbidity. 3,4 Precise treatment decisions help to prevent chronification of UTIs in children, related the development of antibiotic resistance, voiding dysfunctions, renal scarring, and systemic abiosis.
Uropathogens involved in UTIs should be identified with precision to allow targeted therapeutic decisions. 5 In recent years, more and more published clinical case reports have attempted to clarify the clinical manifestation and management strategies of UTIs caused by M. morganii. 6,7 M. morganii is recognized as a new clinical treatment challenge because of ongoing acquisition of antimicrobial resistance genes, which may bring more extensive and challenging multidrug resistance issue. 8 The first study investigating community-acquired UTIs caused by M. morganii in children has been reported in Turkey. 9 Our study aims to explore the risk, antimicrobial susceptibility, and clinical characteristics, so as to improve the treatment and prognosis

| Instruments and reagents
Urine specimens may have originated from clean-catch midstream urine or aseptic bladder catheterizations. Urine samples were inoculated onto eosin methylene blue agar (Autobio Diagnostics Co Ltd.) and Colombian blood agar medium (Autobio Diagnostics Co Ltd.).
All inoculated plates were incubated in Thermo M3111 incubator (Thermo Inc.). Pathogen identifications were performed using the Vitek MS-CHCA (BioMérieux Inc.) and Vitek-MS automated microbial identification system (BioMérieux Inc.). The cut-off used for significant bacterial presence was ≥1000-50,000 colony-forming units (CFU)/ml for urine specimen from bladder catheterization (≥10 4 CFU/ml with symptoms or ≥10 5 CFU/ml without symptoms for urine specimen from midstream void). 10 BioMerieux mini Vidas automated immunoassay analyzer (BioMérieux Inc.) and procalcitonin (PCT) kit were used to detect serum PCT. C-reactive protein (CRP) was detected by VITROS 5,1 FS analyzer (Ortho-Clinical Diagnostics) using the manufacturer's reagents. The new UF-1000i analyzer (Sysmex) was used for urinalysis. The urinalysis with positive leucocyte esterase and/or nitrite, bacteriuria, or pyuria is highly sensitive for UTI.

| Antimicrobial susceptibility testing
Antimicrobial susceptibility testing of M. morganii isolates was determined by the automated VITEK 2 compact microbiology analyzer (BioMérieux Inc.) using antimicrobial susceptibility testing (AST)-GN67 and XN04 cards (BioMérieux Inc.). Results were inter- sensitivity results. Multi-drug resistance was defined as resistance of an isolate to three or more antimicrobial classes tested. 16

| Quality control
The quality control strains of pathogen identification were E. coli ATCC 8739 strains (Biomerieux Inc.). For quality control of susceptibility tests, E. coli ATCC25922 strains (National Center for Clinical Laboratories) were used.

| Ethical clearance
The study was approved by Ethical Review Committee of the   Table 1). Ten cases defined as lower UTIs with no specific clinical manifestations observed had normal or slightly elevated leukocyte counts and PCT levels, and normal  Table 2.
The susceptibility testing demonstrated 72.7% (8/11) susceptibility to ciprofloxacin, moxifloxacin, nalidixic acid, gentamicin, ticarcillin, levofloxacin, but 100% resistance to cefuroxime axetil     to amikacin. Compared to the data of Turkish study, 9 our study proved the same susceptibility rate of meropenem, piperacillin-tazobactam and amikacin, but susceptibility rate of imipenem (44.4%, 4/9) was lower in our survey. Although the exact reasons for conflicting results of imipenem susceptibility are unclear, differences in age, race,

TA B L E 3 Clinical information of patients
Case Antibiotics before urine culture results In summary, our study described that lower UTIs caused by

ACK N OWLED G M ENTS
We would like to acknowledge all staff members for participation in and contribution to this study. We also thank all patients included in this research.

CO N FLI C T O F I NTE R E S T
The authors declare no conflict of interest.

AUTH O R CO NTR I B UTI O N S
Chen Xianrui and Shi Huixuan designed the study. Shi Huixuan analyzed and interpreted the data, and drafted the article. Yao Yonghua and Xu Jinping acquired the data. Chen Xianrui is the corresponding author who contributed to conception and design, critical revision of the article for important intellectual content. All authors read and approved the final manuscript.

DATA AVA I L A B I L I T Y S TAT E M E N T
The data that support the findings of the current study are available from the corresponding author upon reasonable request.