A Rare Case of Multidrug-resistant Leclercia adecarboxylata Catheter-related Bloodstream Infection and an Updated Brief Literature Review

To the editor.

Antibiotic resistance is one of the most relevant problems in hospitals: the growth of resistant microorganisms in healthcare settings is a worrisome threat, raising the length of stay, morbidity, and mortality in patients infected with multidrug resistant bacteria.¹ Moreover, the steady progress in diagnostic techniques is rising concern about the emergence of new pathogens which were hardly known in the past years.

Leclercia adecarboxylata is a gram-negative, motile, facultative-anaerobic, oxidase-negative, mesophilic bacillus belonging to the Enterobacteriaceae family.² L. adecarboxylata was first described by H. Leclerc in 1962 and was previously known as Enteric group 410 or Escherichia adecarboxylata³ since Leclercia spp. shares several structural and microbiological properties with the genus Escherichia. Due to those similarities, L. adecarboxylata infections might be more common than what is believed so far since past clinical cases might have been erroneously defined as Escherichia spp. infections. Moreover, most bacterial assays often could not distinguish these morphologically and metabolically similar bacteria.⁴ Nevertheless, the availability of more sensitive testing methods (e.g., DNA hybridization, computer identification studies) like Matrix Assisted Laser Desorption/Ionization Time of Flight (“MALDI-TOF”) mass spectrometry allowed a more precise species identification, eventually leading to the present categorization.³ L. adecarboxylata can be found in various specimens and is involved in a wide range of clinical syndromes commonly related to immunocompromised hosts. Although most Leclercia spp isolates show high susceptibility to antibiotics, some multi-resistant strains have been reported in the literature. Here, we present a catheter related bloodstream infection caused by a multidrug resistant L. adecarboxylata.

Case Report

A 38-year-old transgender woman affected by gastric and duodenal diffuse large B-cell lymphoma in remission was admitted to our Infectious Diseases Department due to persistent and intense asthenia, weight loss, and recurring fever episodes. The last rituximab administration was performed 4 months before, and the antimicrobic prophylaxis was recently discontinued following bone marrow recovery. The patient assumed total parenteral nutrition through a tunneled central venous catheter (CVC) placed 5 months prior to the admission because of duodenal sub-stenosis subsequent to her hematologic condition. Moreover, she was affected by chronic hepatitis HBV-correlated, treated with tenofovir disoproxil fumarate, and several episodes of syphilis reinfection were recorded following her former sex worker activity. No HIV or HCV co-infections were detected. The chest CT scan performed in the Emergency Department showed a parenchymal and nodular thickening. Considering her risk factors for a healthcare-associated infection, piperacillin/tazobactam (4.5 g every 6 hours/day) was empirically started. At the admission, no catheter dysfunction and no signs of catheter-related infection were recorded, and neither an anti-methicillin-resistant Staphylococcus aureus (MRSA) nor an antimycotic agent was introduced.

A diagnostic bronchoscopy was also performed, but both microbiological tests (serology and cultures) and molecular biology assays performed on the bronchoalveolar lavage gave negative results. However, L. adecarboxylata was isolated from either peripheral and CVC blood culture performed at the hospital admission. Catheter-related bloodstream infection (CRBSI) was then diagnosed since a blood culture drawn from the line was positive 4 hours earlier than the peripheral vein. This result was also consistent with the anamnestic data concerning suboptimal domiciliary management of the CVC, as she referred a sporadic nonsterile handling of the catheter entry site (for instance, contact with tap water). The antibiogram showed resistance to amoxicillin/clavulanate, fosfomycin, and trimethoprim-sulfamethoxazole (Table 1), so piperacillin/tazobactam (MIC ≤1) was maintained, and the catheter was promptly replaced with a peripherally inserted central catheter (PICC). A progressive clinical improvement was observed with a significant reduction in inflammatory markers. On day 14, the targeted systemic antibiotic therapy was discontinued. An esophagogastroduodenoscopy was later performed to assess the severity of the duodenal stenosis. A mass-forming inflammatory non-lymphomatous tissue was observed, and on day 21, a duodenal prosthesis was placed. In the following days, the patient was discharged with a semi-liquid diet and parenteral nutrition to recover a complete oral feeding.

Table 1.

Multidrug-resistant L. adecarboxylata antibiograms (S= susceptible, R= resistant).

	Catheter-drawn blood culture		Peripheral blood culture
Microorganism	Leclercia adecarboxylata		Leclercia adecarboxylata
Incubation period	5 hours		9 hours
		MIC (mcg/ml)		MIC (mcg/ml)
Amikacin	S	2	S	2
Amoxicillin/clavulanic acid	R	>16	R	>16
Cefepime	S	≤0.12	S	≤0.12
Cefotaxime	S	≤0.25	S	≤0.25
Ceftazidime	S	≤0.12	S	≤0.12
Ceftazidime/avibactam	S	≤0.12	S	≤0.12
Ceftolozane/tazobactam	S	≤0.25	S	≤0.25
Ciprofloxacin	S	0.12	S	0.12
Colistin	S	≤0.5	S	≤0.5
Fosfomycin	R	>32	R	>32
Gentamicin	S	≤1	S	≤1
Imipenem	S	≤0.25	S	≤0.25
Meropenem	S	≤0.25	S	≤0.25
Piperacillin/tazobactam	S	≤4	S	≤1
Tobramycin	S	≤1	S	2
Trimethoprim/sulfamethoxazole	R	>160	R	>160

Discussion and Literature Review

Leclercia adecarboxylata is a gram-negative bacillus member of the Enterobacteriaceae family with many structural and microbiological properties in common with the genus Escherichia.^2,3 The reclassification of this bacteria was achieved thanks to more sensitive testing methods such as DNA hybridization and computer identification studies.²

L. adecarboxylata has been recently recognized as an emerging pathogen^3,5 for which, thanks to the currently available diagnostic methods, it is possible to obtain an accurate identification.³ Moreover, several analyses enlighten an ever-increasing number of multidrug-resistant strains^4,5,10 that should highlight the implications of this bacterial infection. L. adecarboxylata is a ubiquitous microorganism that may be found in aquatic environments and soil, as well as in the commensal gut flora of certain animals.² In our case, an exposition to an aquatic environment was identified (use of water to rinse the CVC), similar to a few cases reported in the literature.⁶ Moreover, L. adecarboxylata might also be isolated from blood culture, skin wounds, peritoneal fluid, abscesses (e.g., peritonsillar and periovarian), feces, urine, and synovial fluid.⁸ Several underlying conditions might favor L. adecarboxylata infections: for instance, wounds may act as a direct entry into the tissue, thus easing the pathogenicity, as well as catheters may be used as gateways in catheter-related bacteremia or peritonitis could be developed in patients undergoing dialysis or chemotherapy.⁴

The isolates more commonly mentioned in the literature show a high susceptibility to antibiotics.⁴ They could be controlled with a variety of antibiotics, such as B-lactams, without witnessing therapeutic failures or needing second-line treatments.¹⁰ Considering the EUCAST breakpoint for Enterobacterales and given the contemporary resistance to at least 1 antibiotic of 3 different classes showed in our L. adecarboxylata antibiogram, we consider peculiar our results since, to our best knowledge, only a few cases of resistant strains have been reported.² A more comprehensive evaluation regarding natural antimicrobial susceptibility patterns was reported by Stock et al. from 94 L. adecarboxylata strains collected from several human specimens: the bacteria were naturally resistant to numerous antibiotic molecules, such oxacillin, clarithromycin, erythromycin, roxithromycin, ketolides, rifampin, glycopeptides, streptogramins, fusidic acid, lincosamides, penicillin G and fosfomycin but susceptible to most B-lactams, quinolones, aminoglycosides, tetracyclines, nitrofurantoine, folate pathway inhibitors, azithromycin and chloramphenicol. In addition, Extended-spectrum beta-lactamase (ESBL) and New Delhi metallo-beta-lactamase 1 (NDM)-producing L. adecarboxylata are also described. Three cases of ESBL producer isolates were reported: the first case was described from a patient with acute myeloid leukemia,² the second in a 47-year-old female with breast cancer,¹⁰ and the third one in a 50-year-old female with end-stage renal disease.⁵ Regarding NDM-producing L. adecarboxylata, two cases were reported: the first regarding a patient hospitalized for a foot trauma-related injury, and the second concerned an outbreak of 25 patients in intravenous total parental nutrition.²

L. adecarboxylata might cause monomicrobial infection in immunocompromised patients, while it is thought that this pathogen generally requires other coinfecting bacteria to establish infection in immunocompetent subjects.⁴ However, some cases of monomicrobial infection were described in immunocompetent patients even without significant underlying comorbidities: only in one case the patient report a clinical history of chronic disease,⁸ while in the other cases, no history indicative of a clinically compromised state was observed.⁹ Prevalently, L. adecarboxylata infections are described in adults, but a wound infection and peritonitis were reported in two immunocompetent children.² L. adecarboxylata is implicated in several clinical syndromes, such as endocarditis,² bacteremia,^4,8 wound infection and cellulitis,⁶ pharyngeal and peritonsillar abscesses,⁹ urinary tract infections,³ pneumonia³ and peritonitis.³ Most of these infections, as reported in our case, have been linked to immunosuppression and the simultaneous presence of central vascular catheter.⁸ Additionally, as it appears from several reports, catheters could be considered important reservoirs for L. adecarboxylata bloodstream infection.^5,7,10 As a matter of fact, L. adecarboxyalta is not a fastidious pathogen: our strain grows both on blood and MacConkey agar.

Regarding treatment options, there are no shared guidelines or recommendations for L. adecarboxylata infections. Most isolates described are sensitive to tested antibiotics.⁴ However, as described by Spiegelhauer et al., several strains of L. adecarboxylata displayed resistance to ampicillin (9/30 isolates resistant) and fosfomycin (8/10 isolates resistant), so these antibiotics should not be used as first-line for treatment. Stock et al. described the natural susceptibility patterns of L. adecarboxylata, showing that most isolated strains were sensible to B-lactams. Thus, Leclercia could be treated with this antibiotic class.¹⁰ In our case, considering the multi-resistance pattern, we successfully treated our patient with the administration of piperacillin/tazobactam.