Case Report: Cedecea lapagei Infection: Report of a Case in Peru and Review of the Literature

ABSTRACT.

Cedecea lapagei is a gram-negative, non-encapsulated, facultative anaerobic bacterium that has been reported in only a few cases with varying clinical presentations, drug susceptibility, and treatment since its first isolation in 1981. This study aimed to describe a case report of C. lapagei in Peru and systematically review the documented case reports of individuals infected with C. lapagei. A 59-year-old man who had become bedridden with Parkinson’s disease and had epilepsy presented with a 1-week history of fever and sore throat and was admitted. Physical examination revealed an obtundation state and abolished vesicular murmur in the right hemithorax. During hospitalization, the patient was diagnosed with various infections, including tuberculosis, for which he received broad-spectrum antibiotics. In the absence of clinical improvement, a urine culture was performed showing C. lapagei (detected by BD Phoenix M50 system, Vernon Hills, IL). The patient received amoxicillin/clavulanate and was discharged. Case reports of C. lapagei were also searched in five databases on January 28, 2023. Twenty cases of C. lapagei were reported worldwide between 2006 and 2022, 16 of which involved adults. Fever was the most common manifestation (75%), and pneumonia was the primary form of presentation (45%). Moreover, 90% of the patients had at least one comorbidity, and 15% died. Also, most of the isolates were sensitive to ciprofloxacin (81%), meropenem (62%), and amikacin (60%). Overall, C. lapagei should be suspected in compromised hosts, particularly those with pneumonia. Although the bacterium can affect various organs and the antibiotic susceptibility pattern is variable, quinolones, tetracyclines, and carbapenems seem to be the first therapeutic option.

INTRODUCTION

Cedecea lapagei is a gram-negative, non-encapsulated, facultative anaerobic, lactose-negative, catalase-positive, and non–spore-forming bacterium that belongs to the Enterobacteriaceae family. It was first isolated in 1981.¹ The Cedecea genus consists of five species: Cedecea davisae, Cedecea neteri, Cedecea lapagei, and two other unnamed species.^1,2 The members of the Cedecea genus are usually motile and grow well on nonselective laboratory media, producing convex colonies at 37.1°C. Cedecea lapagei can be distinguished from other Cedecea strains by its growing ability in media lacking thiamine.³ Although it was discovered more than 40 years ago, it was designated a human pathogen in 2006,⁴ and few cases have been reported worldwide.

The distribution of organ involvement is highly variable. According to reports, the infections produced include bacterial peritonitis, pneumonia, bacteremia, and wound infection^2,4–6 and may even lead to septic shock.^7,8 However, C. lapagei does not exhibit a clear tropism and affects different age groups. This bacterium belongs to the gastrointestinal and urinary microbiota and grows in acidic and alkaline conditions (pH 4–10).³ Its transmission mechanism is unknown, even though it could be related to the environment, hospital contacts, host immunity status, use of antimicrobials, or other factors that have not yet been studied.²

The treatment of infections caused by Cedecea strains represents both a challenge and a threat to health systems, especially in low- and middle-income countries owing to their drug resistance patterns. In Peru, where the health system is simultaneously dealing with multiple epidemics (arbovirosis and tuberculosis, among others) and has high antibiotic resistance rates,⁹ the emergence of new bacterial genera with a potentially high resistance profile is important. Hence, this study aimed to systematically review the documented case reports of individuals with C. lapagei. Secondarily, we describe the first case report of C. lapagei in Peru in a patient co-infected with pulmonary tuberculosis.

CASE REPORT

A 59-year-old man, a resident of Lima (the capital of Peru) who had a history of epilepsy and was bedridden secondary to Parkinson’s disease treated with valproate and methyldopa, was admitted to the emergency department. The patient presented with a 1-week history of fever and sore throat, according to a relative.

On admission, his vital signs showed a temperature of 36°C, heart rate of 72 beats/minute, respiratory rate of 24/minute, blood pressure of 82/46 mm Hg, and oxygen saturation of 92%. Physical examination revealed a sacral pressure ulcer grade IV, abolished vesicular murmur in the lower third and mid-third of the right hemithorax, rales in the pulmonary apex and left hemithorax, and diffuse rhonchi. The patient was obtunded, and his Glasgow coma scale score was 11/15. Laboratory results showed mild anemia (hemoglobin 11.4 g/dL), leukocytes 8.11 × 10³/m, platelets 179 × 10³/m, and hyponatremia (sodium 122 mmol/L). An arterial blood gas test revealed metabolic alkalosis with respiratory alkalosis. In addition, the urinalysis showed hematuria and leukocyturia. The blood culture was negative, and the urine culture presented the growth of Proteus mirabilis wild-type. The sputum smear was positive for acid-fast bacilli. A chest x-ray showed reinforcement of the pulmonary interstitium, a micronodular pattern with right predominance, elevation of both hemidiaphragms with right predominance, and the usual placement of a central venous catheter (Figure 1A). Computed tomography of the lung in a tree-in-bud pattern involving the left lower lobe, in addition to bibasilar atelectasis and mediastinal adenopathy (Figures 1B–D).

Figure 1.

Chest x-ray and computed tomography (CT). (A) Chest x-ray in antero-posterior view. (B) Chest CT in coronal view. (C) Chest CT in sagittal view. (D) Chest CT in axial view.

Broad-spectrum antibiotic therapy was initiated with ceftriaxone and clindamycin, which was administered for 12 days. Likewise, the patient received the basic tuberculosis treatment regimen (isoniazid, rifampicin, ethambutol, and pyrazinamide) from the Peruvian Ministry of Health throughout his hospital stay. The patient also received valproate for seizure prevention, and a nasogastric tube and a Foley catheter were inserted. After the initial antibiotic therapy was suspended for 13 days owing to clinical improvement, the patient presented with a fever and decreased consciousness; therefore, a new urine culture was performed and empirical treatment with ceftriaxone was reinitiated. The urine culture showed the growth of extended-spectrum beta-lactamase–producing Escherichia coli (detected by the BD Phoenix M50 system), and the treatment was changed to meropenem.

Nevertheless, in the absence of clinical improvement and persistent fever, another urine culture was performed, showing the growth of C. lapagei. The strain was resistant to cefazolin, cefuroxime, ceftriaxone, cefepime, cefoxitin, imipenem, meropenem, ertapenem, gentamicin, amikacin, trimethoprim/sulfamethoxazole, ciprofloxacin, and levofloxacin. The identification was performed in CLED agar using the Phoenix M50 system (Table 1). According to the susceptibility pattern, the patient received amoxicillin/clavulanate. After 14 days of treatment, the antibiotic was changed to piperacillin/tazobactam plus clindamycin for 5 days to widen antibiotic coverage. The patient was finally discharged and continued outpatient treatment of tuberculosis.

Table 1.

Antimicrobial susceptibility of Cedecea lapagei

Antibiotic	MIC (μg/mL)	Interpretation
Amoxicillin/clavulanate	≤ 8/4	Sensitive
Piperacillin/tazobactam	32/4–64/4	Intermediate
Cefazolin	≥ 8	Resistant
Cefuroxime	≥ 32	Resistant
Ceftriaxone	≥ 4	Resistant
Cefepime	≥ 16	Resistant
Cefoxitin	≥ 32	Resistant
Imipenem	≥ 4	Resistant
Meropenem	≥ 4	Resistant
Ertapenem	≥ 4	Resistant
Gentamicin	≥ 16	Resistant
Amikacin	≥ 64	Resistant
Trimethoprim/sulfamethoxazole	≥ 4/76	Resistant
Nitrofurantoin	64	Intermediate
Ciprofloxacin	≥ 2	Resistant
Levofloxacin	≥ 4	Resistant

MIC = minimum inhibitory concentration.

Mechanism of resistance: serine-based carbapenemases; phenotype MLSb.

MATERIALS AND METHODS

Registration and reporting.

This systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines, and the Cochrane Handbook for Systematic Reviews was used to draft this manuscript.¹⁰ A short version of the protocol was submitted to the International Prospective Register of Systematic Reviews database (ID: CRD42023404648).

Search strategy and databases.

We followed the guidelines of the Peer Review of Electronic Search Strategies for building the search strategy.¹¹ The search formula was based on MeSH, Emtree, and free terms. The search term was “Cedecea lapagei.” The search strategy was modified as needed for all databases.

The systematic search was simultaneously run in all databases from inception to January 28, 2023. We did not apply language restrictions for this systematic review. We searched through the following databases: PubMed, Web of Science, Scielo, Embase, and Scopus, and a manual search was also performed. We have attached the complete search strategy as supplementary material (Supplemental Table 1).

Eligibility criteria.

The case reports of C. lapagei infection in patients of any age were included. Studies that were published as abstracts or letters were also included, provided the available information made data collection possible.

Study selection process and data extraction.

After records were retrieved from all the databases, duplicates were removed using Rayyan QCRI (Rayyan Systems Inc., Cambridge, MA).¹² This software was used for screening by titles and abstracts. Three researchers independently performed this process (P. V.-P., A. A.-C., and J. R. U.-B.). The same researchers independently reviewed the full-text articles from the remaining records. Afterward, two authors (A. A.-C. and J. R. U.-B.) independently extracted the data from each of the included studies in pre-set Google Sheets. We resolved any conflict or discrepancy concerning the inclusion of articles at any stage of the selection process by consensus. The following information was extracted: author; publication date; country; patient’s age, sex, medical diagnosis, clinical presentation, and comorbidities; diagnostic method; antimicrobial susceptibility; antibiotic treatment; and outcome.

Quality assessment.

The quality assessment of case reports was performed with the Joanna Briggs Institute’s critical appraisal tool for case reports.¹³ A score of seven or more stars was deemed to have a low risk of bias, whereas a score of six or fewer stars was deemed to have a high risk of bias.

RESULTS

Search results.

The systematic search retrieved a total of 101 records, of which 63 duplicates were removed. According to the inclusion criteria, after articles were excluded by title/abstracts and full-text articles were assessed, 20 articles were identified as eligible for this systematic review.^{4–8,14–28} The detailed flow chart of the literature selection is shown in Figure 2.

Figure 2.

Flowchart of included studies.

Quality assessment.

In the quality assessment of the case reports, all studies were found to have a low risk of bias (Supplemental Table 2).

Study characteristics.

The characteristics of the case reports are summarized in Table 2. Of the 20 case reports included (17 males and 3 females), 4 cases were reported in children under 1 year and the rest in adults (> 18 years). The reports were published between 2006 and 2022. Most of the cases were reported in countries from Asian and American continents (Figure 3).

Table 2.

Summary of clinical cases of Cedecea lapagei

Author	Year	Country	Age	Sex	Medical diagnosis	Clinical presentation	Comorbidities	Diagnostic method	Antimicrobial susceptibility testing (antibiogram)	Antibiotic treatment	Outcome
Duperret et al.14	2020	United States	45	Male	Sinusitis	Foul rhinorrhea, sinus headache, and fever	Asthma	Culture from purulent nasal secretions	Resistant to: amoxicillin/clavulanate, ampicillin, and cefazolin Sensitive to: ciprofloxacin, gentamicin, meropenem, tetracycline, and tobramycin Intermediate sensitivity to: cefuroxime	Oral ciprofloxacin + nasal gentamicin/dexamethasone	Patient recovered (discharged)
Hai et al.7	2020	Vietnam	38	Male	Pneumonia and septic shock	Fatigue, cough, sputum, myalgia, fever, and shortness of breath	Diabetes mellitus type 2	Sputum culture	Resistant to: trimethoprim/ sulfamethoxazole Sensitive to: piperacillin/ tazobactam, ceftazidime, ceftriaxone, cefazolin, cefoxitin, aztreonam, imipenem, meropenem, amikacin, gentamicin, tobramycin, levofloxacin, and ciprofloxacin Intermediate sensitivity to: piperacillin	IV meropenem + IV ciprofloxacin	Patient recovered (discharged)
Ramaswamy et al.15	2019	India	35 days	Male	Nosocomial pneumonia and sepsis	Poor peripheral pulses, lethargy, fever, and severe respiratory distress	Late preterm	Blood culture	Resistant to: meropenem, colistin, amikacin, gentamycin, and ceftazidime Sensitive to: piperacillin, piperacillin/ tazobactam, trimethoprim/ sulfamethoxazole, ciprofloxacin, and levofloxacin	IV piperacillin/ tazobactam	Patient recovered (discharged)
Chavez Herrera et al.16	2018	Mexico	52	Male	Infection of hemorrhagic bullae causing necrotizing fasciitis and septic shock	Fever, pain, edema in his right lower limb, and multiple organ failure	Liver cirrhosis and treated hypertension	Bullae fluid culture	Resistant to: ampicillin, cefazolin, and imipenem Sensitive to: amikacin, aztreonam, ceftriaxone, ceftazidime, cefotaxime, ciprofloxacin, cefepime, cefuroxime, cefotetan, gentamicin, levofloxacin, meropenem, moxifloxacin, and piperacillin/ tazobactam Intermediate sensitivity to: ampicillin/sulbactam	IV clindamycin + IV ceftriaxone	Death
Kury et al.17	2017	Brazil	110 days	Male	Ventilator-associated pneumonia and sepsis	Fever and yellow sputum	Ischemic encephalopathy sequelae and chronic lung disease	Cultures from blood and tracheal aspirates	Resistant to: NR Sensitive to: piperacillin, imipenem, amikacin, gentamycin, ciprofloxacin, levofloxacin, meropenem, and trimethoprim/ sulfamethoxazole	IV meropenem	Patient recovered (discharged)
Biswal et al.18	2015	India	50	Male	Ulcer and pus formation at the cancer site	Fever and pain at the local site of ulcer, radiating to ear and forehead	Squamous cell carcinoma of the right buccal mucosa undergoing chemotherapy	Culture of pus samples from the ulcer site	Resistant to: ampicillin/sulbactam, tetracycline, and tigecycline Sensitive to: amikacin, gentamicin, ceftazidime, ceftriaxone, cefepime, ciprofloxacin, meropenem, and trimethoprim/ sulfamethoxazole	IV ciprofloxacin	Patient recovered (discharged)
Salazar et al.6	2013	Ecuador	24	Male	Traumatic wound infection	Fever, poor condition of healing tissue, increased discharge, and bad odor	No comorbidities	Culture of secretion obtained from granulation tissue	Resistant to: ampicillin and ampicillin/ sulbactam Sensitive to: cefuroxime, amikacin, trimethoprim/ sulfamethoxazole, ciprofloxacin, cefotaxime, carbapenems	IV ampicillin/sulbactam	Patient recovered (discharged)
Hong et al.19	2015	South Korea	76	Male	Pneumonia	Fever and dyspnea	Chronic obstructive pulmonary disease	Sputum culture	Resistant to: amoxicillin/clavulanate and cefoxitin Sensitive to: piperacillin, cefotaxime, ceftazidime, cefepime, imipenem, amikacin, ciprofloxacin, tetracycline, and trimethoprim/ sulfamethoxazole	IV cefpodoxime	Patient recovered (discharged)
Sanchez-Lopez et al.5	2013	Mexico	34	Male	Pneumonia	Fever, dyspnea, bilateral alveolar infiltrates, copious yellow sputum, and disseminated intravascular coagulation	Acute promyelocytic leukemia	Sputum culture	Resistant to: amikacin, ampicillin, aztreonam, cefazolin, cefepime, ceftriaxone, ciprofloxacin, ertapenem, imipenem, meropenem, moxifloxacin, nitrofurantoin, piperacillin/ tazobactam, and trimethoprim/ sulfamethoxazole Sensitive to: tigecycline Intermediate sensitivity to: ampicillin/sulbactam, gentamicin, and tobramycin	IV cefepime + IV vancomycin	Patient recovered (discharged)
Yetkin et al.20	2008	Turkey	38	Male	Pneumonia from the aspiration of upper airway secretion	Fever, dyspnea	Subarachnoid hemorrhage and chronic obstructive pulmonary disease	Culture from bronchoalveolar lavage fluid	Resistant to: amoxicillin, ampicillin, amoxicillin/clavulonate, and cephalothin Sensitive to: amikacin, ciprofloxacin, trimethoprim/ sulfamethoxazole, imipenem, aztreonam, cefepime, ceftriaxone, ceftazidime, cefotaxime, cefuroxime, piperacillin / tazobactam, gentamicin, piperacillin, and tetracycline	IV amikacin + IV vancomycin + IV meropenem	Death
Dalamaga et al.21	2008	Greece	47	Male	Wound infection	Fever, full-thickness burns in the right knee, and erythema, vesicles, and ulcerations in the left knee	Diabetes mellitus type 2	Blood and wound cultures	Resistant to: gentamicin, tobramycin, cephalothin, cefuroxime, cefoxitin, ceftazidime, tetracycline, and ampicillin Sensitive to: amikacin, meropenem, cefotaxime, cefepime, aztreonam, amoxicillin/clavulanate, piperacillin/tazobactam, trimethoprim/ sulfamethoxazole, ciprofloxacin, and levofloxacin	IV cefotaxime + IV amikacin	Patient recovered (discharged)
Davis and Wall4	2006	United States	55	Male	Peritonitis	Fever, abdominal pain, and cloudy dialysis effluent	Hypertension, orthotopic liver transplantation secondary to cirrhosis related to hepatitis C, continuous peritoneal dialysis, and end-stage renal disease secondary to glomerular disease	Culture from peritoneal fluid	NR	IV vancomycin + IV gentamicin	Patient recovered (discharged)
Mohamud et al.22	2022	Somalia	55	Male	Urinary tract infection	Acute exacerbations of renal failure and irritative voiding symptoms	Chronic renal failure, uncontrolled diabetes mellitus type 2, and hypertension	Culture from urine	Resistant to: ceftriaxone, cefazolin, ceftazidime, cefixime, ampicillin, and amoxicillin/clavulanate Sensitive to: amikacin, gentamicin, trimethoprim/ sulfamethoxazole, ciprofloxacin, levofloxacin, imipenem, and ertapenem	Oral levofloxacin	Patient recovered (discharged)
Cárdenas et al.23	2015	Colombia	47	Male	Acute osteomyelitis	Fever, edema, and erythema in the surgical area	No comorbidities	Culture from bone biopsy	Sensitive to: ertapenem	IV oxacillin + rifampicin empirically, switched to ertapenem after culture	Patient recovered (discharged)
Arellano Aguilar et al.28	2016	Mexico	67	Female	Bacteremia and burns on 20% of body surface	Burns in the granulation stage with moderate edema	Diabetes mellitus type 1, hypertension, and dyslipidemia	Culture from bronchial aspirate and blood culture	Resistant to: ampicillin, amikacin, and piperacillin/ tazobactam Sensitive to: meropenem and imipenem	IV piperacillin/ tazobactam + caspofungin initially, switched to linezolid on day 20 + imipenem/cilastatin on day 24	Patient recovered (discharged)
Çekin et al.24	2014	Turkey	40	Male	Urinary tract infection	Fever	Quadriplegia and use of urinary catheter	Culture from urine	Resistant to: ampicillin, gentamicin, tobramycin, cefazolin, cephalothin, amikacin, ampicillin/sulbactam, ertapenem, imipenem, meropenem, piperacillin, piperacillin/ tazobactam, cefepime, cefoxitin, cefotaxime, cefuroxime, and aztreonam Sensitive to: ciprofloxacin, levofloxacin, and trimethoprim/ sulfamethoxazole	IV ciprofloxacin	Patient recovered (discharged)
Islam et al.25	2016	India	First hours of life	Female	Sepsis with pneumonia	Respiratory distress immediately after birth	Meconium-stained amniotic fluid and low birth weight	Blood culture	Resistant to: amoxicillin/clavulonate, ceftazidime, ceftriaxone, trimethoprim/sulfamethoxazole, gentamycin, cefuroxime, and piperacillin/tazobactam Sensitive to: ciprofloxacin and imipenem	IV amikacin + IV ciprofloxacin	Patient recovered (discharged)
Ahmad et al.8	2017	India	26 days	Female	Late-onset sepsis	NR	Preterm, apnea	Blood culture	Resistant to: imipenem, meropenem, aztreonam, ceftazidime, cefotaxime, cefoxitin, cefepime, and cefoperazone/sulbactam	IV cefotaxime + IV amikacin	Patient recovered (discharged)
Deveci and Arpag26	2021	Turkey	76	Male	Pneumonia	Fever, shortness of breath, cough, sputum, wheezing, and impaired consciousness	COVID-19 2 weeks ago	Sputum culture	Resistant to: amoxicillin/clavulanate, piperacillin/ tazobactam, cefuroxime, cefuroxime acetil, ceftriaxone, ceftazidime, cefepime, amikacin, gentamicin, ciprofloxacin, tigecycline, and colistin Intermediate sensitivity to: meropenem and trimethoprim/ sulfamethoxazole	IV meropenem + IV moxifloxacin	Patient recovered (discharged)
González Rivera et al.27	2022	Mexico	57	Male	Pneumonia and septic shock	Fever, dyspnea, decreased amplection, use of accessory musculature with oxygen through nasal prongs at 5 L per minute, increased vocal vibrations on palpation, and bilateral infrascapular crepitant rales	HIV treatment discontinuation for the last 3 years	Culture from bronchial aspirate	Resistant to: ampicillin, gentamicin, tobramycin, cefazolin, cephalothin, amikacin, ampicillin/sulbactam, ertapenem, imipenem, meropenem, piperacillin, cefepime, cefotaxime, cefuroxime, aztreonam, ciprofloxacin, levofloxacin, and trimethoprim/ sulfamethoxazole	NR	Death

IV = intravenous; NR = not reported. Age is shown as years unless otherwise noted.

Figure 3.

Geographical distribution of Cedecea lapagei studies. Countries where C. lapagei was isolated are shaded in dark grey. (Source: Blank map political world territories.png [June 10, 2017]. Wikimedia Commons, the free media repository. Available at: https://commons.wikimedia.org/wiki/File:Blank_map_political_world_territories.png. Accessed March 8, 2023.)

Fever was the most common manifestation (75%). There were many forms of presentation, the most common being pneumonia (45%), followed by sepsis (20%) and septic shock (15%), whereas skin involvement was present in four cases and one case reported osteomyelitis. Cedecea lapagei was most frequently isolated from blood culture (30%), followed by sputum (20%) and bronchoalveolar lavage (20%). Although comorbidities were variable, 90% of cases had at least one comorbidity. All reports of children under 6 months of age were associated with septic shock or sepsis. Death was reported in 15% of cases (Table 2).

Antibiotic susceptibility was tested in 95% of cases. Most isolates were tested for susceptibility to ciprofloxacin: of 16 isolates, 3 showed resistance (18.8%). Most of the isolates were sensitive to levofloxacin (87.5%), ciprofloxacin (81.3%), cefotaxime (71.4%), trimethoprim/sulfamethoxazole (69.2%), meropenem (61.5%), imipenem (61.5%), amikacin (60%), and gentamicin (53.8%). On the other hand, all isolates were resistant to ampicillin (N = 10), cephalothin (N = 4), colistin (N = 2), nitrofurantoin (N = 1), cefuroxime acetil (N = 1), cefoperazone/sulbactam (N = 1), cefixime (N = 1), and amoxicillin (N = 1) (Figure 4). Regarding antibiotic treatment, most patients received ciprofloxacin (25%), followed by meropenem (20%) and amikacin (20%) (Figure 5).

Figure 4.

Susceptibility of clinical isolates of Cedecea lapagei to tested antibiotics.

Figure 5.

Antibiotics used for treatment of Cedecea lapagei infections.

DISCUSSION

This is the first case report of C. lapagei in Peru, involving a patient who was coinfected with tuberculosis and had epilepsy and a bedridden state secondary to Parkinson’s disease. The bacterium strain was extensively drug resistant, and the phenotype was MLSb. In addition, this is the first systematic review of cases of C. lapagei. A total of 20 cases were reported worldwide between 2006 and 2022, mainly in the Asian and American continents. Most patients had comorbidities, and 15% died.

Our case report revealed an extensive antibiotic resistance pattern, which is in line with the high rates of antimicrobial drug resistance reported in Peru.⁹ The patient had a lengthy hospital stay and was exposed to several broad-spectrum antibiotics before the isolation of C. lapagei. Both of these factors have been associated with an increased risk of antibiotic resistance, mainly the use of beta-lactams such as ceftriaxone or carbapenems, which our patient received.^29,30 The most concerning aspect of the clinical case was the presence of pulmonary tuberculosis, which is an endemic public health concern in Peru.³¹ This raises concern because the emergence of new bacterium outbreaks in low- and middle-income countries represents a latent threat owing to the vulnerability of their health care systems.

Most patients in our review had comorbidities that pose a significant risk factor for opportunistic infections. This is a common characteristic of the Cedecea species.³² Although it is too early to determine with certainty which comorbidities are associated with infection by this bacterium, it is clear that it affects mainly immunocompromised individuals, and further studies are needed to clarify this topic. Likewise, different species of Cedecea have been isolated from invasive medical devices such as central venous catheters and urinary catheters.^33–35 This suggests the possible role of biofilm in its pathogenicity; thus, the isolation of C. lapagei from an invasive device should not be underestimated, mainly in immunocompromised hosts or those with multiple comorbidities, such as our patient who had a urinary catheter in a nosocomial environment.

The antibiotic susceptibility pattern was variable among the isolates of C. lapagei. Although some antibiotic classes such as quinolones, tetracyclines, and carbapenems were the most sensitive, most isolates were resistant to penicillin and cephalosporins. This pattern is in line with the results of another review of Cedecea species.³² Consequently, most patients in our review received quinolones, tetracyclines, and carbapenems. Interestingly, the patient in our case report was resistant to all these groups except for amoxicillin/clavulanate. This highlights the importance of antibiotic susceptibility testing in directing therapy because of this bacterium’s variability.

There is little information on the mechanisms of resistance to antibiotics in Cedecea. Beta-lactamases have been reported as the main resistance mechanism in C. lapagei. Some of the genes detected were bla_NDM-1, bla_CTX-M, bla_SHV, and bla_TEM. A new ampC beta-lactamase–named CDA-1 combined with porin deficiency (with electrophoretic properties of E. coli ompC and ompF porins) has also been reported in C. davisae, which produced a carbapenem-resistant phenotype.³⁶

Likewise, sequencing of the complete genome of C. neteri³⁵ has shown the presence of multiple open reading frames with sequence similarity to ampC-type beta-lactamases (probably inducible) and four metallo-beta-lactamase–related proteins. Hence, the presence of some of these chromosomal enzymes in C. lapagei is not ruled out. It has also been observed that isolates of Cedecea possess natural resistance to colistin (Polymyxin E), probably associated with modifications of lipopolysaccharides by cationic substitution in their genome containing mgrB, phoP, and phoQ. However, no plasmid DNA has been found, which decreases the possibility of MCR-1 (mobilized colistin resistance) derived from the plasmid.³⁷

Our study’s limitations should be taken into account when interpreting the results. The main limitation of our case report is the inability to identify the bacterium by 16S ribosomal RNA gene sequencing and resistance genes, as this molecular technique is not available in our hospital. Nevertheless, a recent study reported that the BD Phoenix M50 system performs reliably for antibiotic susceptibility testing in clinical microbiology laboratories.³⁸ Regarding the systematic review, the case reports were not standardized; thus, some variables were not reported. In addition, because the reports were not representative of the population, it was not possible to gather data or report rates, ratios, incidence, or prevalence. Thus, our findings do not imply a cause-effect relationship and cannot be generalized.

CONCLUSION

Cedecea lapagei should be suspected in compromised hosts, particularly in those with pneumonia. Nevertheless, further reports on this bacterium are needed as it can affect several organs and its antibiotic susceptibility pattern is variable. Thus, individualized therapeutic management is required for each case. Given the emergence of this bacterium in new latitudes, microbiology laboratories need to be properly equipped to isolate it. Quinolones, tetracyclines, and carbapenems seem to be the first therapeutic option, and our findings suggest that mortality due to this bacterium is low.

Note: Supplemental tables appear at www.ajtmh.org.