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Review

The Emergence of the Genus Comamonas as Important Opportunistic Pathogens

Department of Applied Sciences, Technological University of the Shannon Midwest, Moylish, V94 EC5T Limerick, Ireland
*
Author to whom correspondence should be addressed.
Pathogens 2022, 11(9), 1032; https://doi.org/10.3390/pathogens11091032
Submission received: 28 June 2022 / Revised: 15 August 2022 / Accepted: 8 September 2022 / Published: 12 September 2022
(This article belongs to the Section Bacterial Pathogens)

Abstract

:
Comamonas spp. are non-fermenting Gram-negative bacilli. They were first discovered in 1894, and since then, twenty-four species have been characterized. The natural habitat of these bacteria is soil, wastewater/sludge, fresh water such as ponds and rivers, and the animal intestinal microbiome. They were also isolated from industrial settings, such as activated sludge and polluted soil, and from the hospital environment and clinical samples, such as urine, pus, blood, feces, and kidney. Comamonas spp. are associated with environmental bioremediation and are considered an important environmental bacterium rather than a human pathogen. However, in the 1980s, they became a concern when several human infections associated with these species were reported. Here, the Comamonas genus was examined in terms of its members, identification techniques, and pathogenicity. Seventy-seven infection cases associated with these microorganisms that have been discussed in the literature were identified and investigated in this project. All relevant information regarding year of infection, country of origin, patient information such as age, sex, underlying medical conditions if any, type of infection caused by the Comamonas species, antibiotic susceptibility testing, treatment, and outcomes for the patient were extracted from case reports. The findings suggest that even though Comamonas spp. are thought of as being of low virulence, they have caused harmful health conditions in many healthy individuals and even death in patients with underlying conditions. Antimicrobial treatment of infections associated with these species, in general, was not very difficult; however, it can become an issue in the future because some strains are already resistant to different classes of antibiotics. Therefore, these pathogens should be considered of such importance that they should be included in the hospital screening programs.

1. Introduction

The growing range of severe infections caused by little-known non-fermenting Gram-negative rods is developing into a major cause of concern. These pathogens are opportunistic, infecting patients undertaking medical treatments in hospital and immunocompromised individuals outside of clinical locations. Bacterial species, including Ralstonia spp., Ochrobactrum spp., Pseudomonas aeruginosa, Sphingomonas paucimobilis, and Brevundimonas spp., all belong to this group [1,2,3,4,5,6]. Other emerging Gram-negative, non-fermenting rod bacteria that can cause potentially severe infections are members of the β-proteobacterial genus Comamonas [7].
Comamonas spp. have been isolated from a broad variety of environments, including water, aircraft water, soil, plants, and animals [8,9,10,11,12]. Several Comamonas spp. have been investigated for their potential to degrade xenobiotic pollutants and for heavy metal detoxification under a variety of environmental conditions [13,14,15,16,17,18,19]. Comamonas spp. are thought to be of low virulence. They have, however, caused infections, including serious infection such as septicemia or endocarditis, in immunocompetent hosts [20,21,22].
Analysis of the scientific/medical literature showed wide-ranging types of infections resulting from Comamonas spp. These were resistant to numerous different antibiotics. The data uncovered that this genus is a more commonplace pathogen than hitherto believed, with numerous infections/conditions caused by Comamonas spp. being severe and incapacitating. The purpose of this study was to give a general summation of infections caused by Comamonas spp., any underlying disorders/illnesses in patients that predispose them to infections with these bacteria and the antibiotic therapies that can be used for the management of these infections to aid medical professionals.

2. Genus Comamonas

Previously designated as Pseudomonas rRNA homology group III, the family Comamonadaceae now includes the genera Comamonas, Delftia and Acidovorax. The genus Comamonas, assigned to the Comamonadaceae lineage in the β-Proteobacteria, was originally proposed by Davis and Park [23] and the name validly published with the revival of the genus and the type species Comamonas terrigena by De Vos et al. [24]. In 1987, two Pseudomonas species, Pseudomonas acidovorans and Pseudomonas testosterone, were transferred to the genus Comamonas as Comamonas acidovorans and Comamonas testosteroni, respectively [24]. Based on a detailed 16S rRNA gene sequence-based phylogenetic study of the Comamonadaceae C. acidovorans was transferred as a type species to the novel genus Delftia as Delftia acidovorans [25]. Since then, the Comamonas genus has expanded to 24 species (see Table 1). The phylogenetic relationship between all Comamonas spp. described to date is presented in Figure 1.

3. Identification of Comamonas spp.

The Comamonas species are Gram-negative and comprised of straight or slightly curved rods or spirilla. They are usually 0.5 to 2 by 1 to 6 µm. They are generally motile by means of polar or bipolar tufts of 1–5 flagella (excepting C. koreensis). They are aerobic and chemoorganotrophic (De Vos et al., 2015) [50]. Some of the species are non-pigmented, some appear to be cream or yellow-white in color, and some can produce a brown halo around them (Willems and De Vos, 2006) [51], but they do not produce fluorescent pigments. Colonies appear pink-pigmented with a slimy and convex surface on blood agar. No hemolysis was observed on blood and chocolate agar. They are aerobic, oxidase and catalase-positive, non-spore formers, glucose non-fermenters, and chemoorganotrophic. Good growth was observed on media that contained peptone, organic acids, and amino acids (Public Health England, 2015) [52].

4. Comamonas spp. Virulence

Comamonas spp. are believed to be of low virulence. A study of the pangenome of 34 Comamonas genomes, however, showed that they have a diverse array of virulence factors, including polysaccharide biosynthesis for adherence and anti-phagocytosis, a motility system and metabolic enzymes for adaptation in vivo. All sequenced, clinically-isolated Comamonas strains and a number of environmental Comamonas spp. contain hemolysin genes. These analyses indicated that virulence might be species-specific as certain virulence factors are conserved in pathogenic-like strains [53].

5. Comamonas spp. Outbreaks

The overall knowledge gained from research into the scientific and medical literature can be seen in Table 2, Table 3 and Table 4. These tables show the year when the infection happened (if not available, the year of publication was used), country where the infection happened, patient information (age, sex, any reported underlying medical conditions), type of infection caused by the Comamonas infection, antimicrobial testing (susceptibility and resistance), treatment (focusing on the antibiotic therapies used) and patient outcome.
Table 2, Table 3 and Table 4 illustrate 77 instances of infection caused by Comamonas spp. that were found in literature sources. It was found that only five Comamonas species (out of 24 species so far identified) have caused infections in humans. Most of these infections were caused by Comamonas testosteroni (50 instances—65.3%), other infections were due to Comamonas kerstersii (23 instances—29.8%), Comamonas aquatica (1 instance—1.3%), Comamonas thiooxydans (1 instance—1.3%), and Comamonas terrigena (1 instance—1.3%). In 47 instances (61%) out of 76, the patients had underlying conditions. Twenty different types of infection were caused by the different Comamonas species. These included pneumonia, polymicrobial bacteremia, bacteremia/septic shock, purulent meningitis, and sepsis.
Most patients had one underlying condition, seven had patients with two underlying conditions, and eight had patients with multiple underlying conditions (for example, obesity and diabetes). The most abundant of these underlying conditions were diabetes (in 8 patients—10.3%), various types of cancer (in 5 patients—6.5%) and alcoholism (in 4 patients—5.2%). Other major underlying conditions included obesity (in 3 patients—3.9%), hypertension (in 4 patients—10.9%), and renal failure (in 3 patients—3.9%). A full list of underlying conditions can be seen in Table 2, Table 3 and Table 4. A total of 70 patients (92.1%) were treated successfully and recovered fully, and 6 patients (7.8%) died. All patients who died due to Comamonas spp. infection suffered from one or more underlying conditions. These cases are discussed in more detail below. Surprisingly, to date, no pseudo-outbreaks have been found associated with Comamonas spp.
Most of the reported infections caused by Comamonas spp. appear to be community-acquired [22].

Death Associated with Comamonas spp. Infection

Six instances of death associated with Comamonas spp. infection have been reported. All six cases were linked to C. testosterone (Table 2). The first two instances were reported by Barbaro et al. [54]. In one of these instances, a mother who was an intravenous drug abuser gave birth to a premature baby, and this newborn baby died of sepsis caused by C. testosteroni infection 24 h after he was born. The second instance was very similar as it was also associated with sepsis due to C. testosteroni infection in a premature baby who was stillborn by an intravenous drug abuser mother. The third instance of death was reported in 2008 by Jin et al. [55]. In this case, a 54-year-old homeless man alcoholic was hit by a car, he received multiple fractures of the facial bones and was hospitalized. He was diagnosed with multiple cerebral and cerebellar infarcts, which resulted in changed mental status. He died 15 days after the injury. An autopsy revealed diffuse purulent meningitis due to C. testosteroni infection. In the fourth instance reported by Swain and Rout, a 50-year-old woman who suffered from diabetes and had a chronic renal disease was hospitalized for bacteremia and septic shock [56]. She was treated with piperacillin-tazobactam antibiotics until C. testosteroni was identified. The microorganism was found to be resistant to piperacillin–tazobactam, so treatment was then changed to cefoperazone–sulbactam. However, despite this, the woman died due to septic shock. The fifth instance of death associated with Comamonas spp. was reported in 2017 by Yasayancan and Koseoglu [57]. A 68-year-old man with lung cancer and adrenal metastasis was diagnosed with polymicrobial bacteremia due to C. testosteroni, Staphylococcus haemolyticus, and Acinetobacter baumannii infection. The patient died on the 16th day, despite suitable treatments against these pathogens. The last reported instance of death due to C. testosteroni infection was reported in 2018 by Cetin et al. A 10-year-old boy with serious underlying conditions (cerebral palsy, scoliosis, and long-term support with home mechanical ventilation) was diagnosed with pneumonia due to C testosteroni infection [58]. The patient was treated with appropriate antimicrobial therapy, and after 21 days of treatment infection was cured but due to the patient’s poor health conditions, he died on day 50 of hospitalization. No deaths have been associated with C. kerstersii or any other Comamonas spp (Table 3 and Table 4).
Table 2. Incidences of Comamonas testosteroni infection from 1987 to 2022. Main characteristics of the case reports.
Table 2. Incidences of Comamonas testosteroni infection from 1987 to 2022. Main characteristics of the case reports.
Author (Ref.)YearSex/AgeCountryCo-MorbidityType of InfectionSusceptible to *Resistance to *Antibiotic TreatmentOutcome
Atkinson et al. 1975 [59]1966F/31 yr oldUSARheumatic heart diseaseSepticemiaN/AN/AKanamycin, TetracyclineFull recovery
Grover Smith, 1979 [60]1979M/48 yr oldUSAAtrophic
right leg
Pyarthrosis
Septicemia
Amikacin, Ampicillin,
Carbenicillin, Cephalothin, Chloramphenicol, Colistin, Gentamicin, Kanamycin, Tetracycline, Tobramycin
N/ACephalothin, Gentamicin. Followed by Ampicillin
for 21 days.
Full recovery
Barbaro et al., 1987 [54]1983M/31 yr oldUSANonePerforated appendixN/AN/ACefoxitin then drainage, then Ampicillin, Clindamycin, GentamicinFull recovery
Barbaro et al., 1987 [54]1983M/11 yr oldUSANonePerforated appendixN/AN/AAmpicillin, Clindamycin, TobramycinFull recovery
Barbaro et al., 1987 [54]1983F/59 yr oldUSAAlcoholicCirrhosisN/AN/ACefoxitinFull recovery
Barbaro et al., 1987 [54]1983F/24 yr oldUSAIv drug abuseMeningitisN/AN/AMoxalactam, NafcillinFull recovery
Barbaro et al., 1987 [54]1984F/21 yr oldUSAPregnantPerforated appendicitisCefoxitinN/ASurgery, Iv Cefoxitin for 9 daysFull recovery
Barbaro et al., 1987 [54]1984F/12 yr oldUSANonePerforated appendicitisN/AN/ACefoxitinFull recovery
Barbaro et al., 1987 [54]1985F/84 yr oldUSACongestive heart failureUrine tract infectionN/AN/AAmpicillinFull recovery
Barbaro et al., 1987 [54]1985M/24 yr oldUSANonePerforated appendicitisN/AN/ACefoxitinFull recovery
Barbaro et al., 1987 [54]1985F/New-bornUSAMaternal IV drug abuse, Premature birthSepsisN/AN/AAmpicillin, amikacinDied
Barbaro et al., 1987 [54]1985StillbornUSAMaternal IV drug abuse, premature birthSepsisN/AN/ANoneDied
Franzetti et al., [61]1992N/AItalyAIDSRespiratory infectionN/AN/ACeftazidimeFull recovery
Le Moal et al., 2001 [62]2001F/75 yr oldFranceBreast cancerBacteremiaAztreonam, Ceftazidime, Piperacillin, TicarcillinAmikacin, Ciprofloxacin, FosfomycinCeftazidime, Gentamicin for 10 daysFull recovery
Arda et al., 2003 [63]2003M/50 yr oldTurkeyUndergone cholesteatoma operationPurulent meningitisCeftriaxone, Ceftazidime, MeropenemN/ACeftriaxone (were 3 mg/mL), Ceftazidime (0.75 mg/mL), and Meropenem (0.47 mg/mL), then changed to Meropenem, 3 g/day and operation to remove the cholesteatomaFull recovery
Smith et al., 2003 [64]2003M/89 yr oldUSAN/ABacteremiaN/AN/ALevofloxacinFull recovery
Cooper et al., 2005 [22]2005M/49 yr oldUSANoneEndocarditisAmpicillin, Gentamicin, first, second, third generation Cephalosporins, Imipenem, Ciprofloxacin, Levofloxacin, Piperacillin, SXT, TobramycinN/AInitially Cefipime, Gentamicin, switched to Ampicillin, then followed by surgery and 6 weeks of IV antibiotic treatmentFull recovery
Gul et al., 2007 [65]2006M/22 yr oldTurkeyNoneBacteremia due to perforated appendicitisAmpicillin/Sulbactam, Amikacin, Cefazolin, Ceftazidime, Cefepime, Ciprofloxacin, Gentamicin, Imipenem, Levofloxacin, Piperacillin-Tazobactam, Imipenem, Meropenem, SXT, TobramycinN/AIv Cefazolin 1 g was given before surgery, Iv Cefazolin 1 g every 8 h after surgeryFull recovery
Abraham and Simon, 2007 [7]2007F/54 yr oldUSAMetastatic esophageal cancer, an indwelling central venous catheterBacteremia, septic shockN/AN/ACefepime, Vancomycin, Azithromycin, Drotrecogin alfa, Glucocorticosteroids, Norepinephrine Vasopressin, then was changed to Cefepime and Ciprofloxacin for 16 daysFull recovery
Garolo et al., 2007 [66]2007M/63 yr oldPolandLumbar discectomySpondylodiscitisN/AN/AEicoplanine (600 mg e.v./day), Ciprofloxacin (400 mg 2 times/day), then Ciprofloxacin, CotrimoxazoleFull recovery
Jin et al., 2008 [55]2008M/54 yr oldUSAAlcoholicPurulent MeningitisN/AN/AMoxifloxacinDied
Reddy et al., 2009 [67]2009F/82 yr oldIndiaDiabetes, Cataract surgeryPost-operative endophthalmitisCeftazidime, Chloramphenicol, Ciprofloxacin, Gatifloxacin, Moxifloxacin, OfloxacinAmikacin, Gentamicin, TobramycinIntraocular injection of 1 mg Vancomycin and 1 mg Ceftazidime, Ciprofloxacin (oral and topical), steroids (oral and topical) and Cycloplegics then intravitreal Ceftazidime (1 mg), topical ceftazidimeFull recovery
Katırcıoğlu et al., 2010 [68]2010M/83 yr oldTurkeyHypertension and ischemic cerebrovascular incidentSepsisAmikacin, Ciprofloxacin, Piperacillin-TazobactamAztreonam, Cefepime, Ceftriaxon, Ceftazidime, Cefoperazon-Sulbactam, Tobramycin, ImipenemPiperacillin-Tazobactam, Amikacin for 10 daysFull recovery
Nseir et al., 2011 [69]2011F/64 yr oldIsraelDiabetes mellitus Patient on hemodialysisBacteremia (Catheter-related)Ceftazidime, Gentamycin, QuinolonesAmpicillin Penicillin, Rocephin.Vancomycin, ceftriaxoneDied
Ozden et al., 2011 [70]2011M/10 yr oldTurkeyCerebral palsy, tracheostomyInfectionN/AN/ACeftriaxone, clarithromycinFull recovery
Tsui et al., 2011 [71]2011M/73 yr oldTaiwanChronic hepatitis B, liver cirrhosis, hepatocellular carcinomaBacteremiaN/AN/ARadiofrequency ablation for liver tumor, Cefmetazon (1 g every 8 h), Gentamicin (60 mg every 8 h), then changed for IV Levofloxacin (500 mg once a day), oral Levofloxacin (500 mg every day) for 4 daysFull recovery
Tsui et al., 2011 [71]2011M/54 yr oldTaiwanAlcoholic, Mild obstructive lung disease, replaced hip jointsBacteremiaN/AN/AIv Oxacillin (2 g every 6 h), Cephalosporin, then IV Ciprofloxacin (400 mg for every 12 h) 8 daysFull recovery
Farshad et al., 2012 [72]2010M/10 yr oldIranBrain Medullo-blastoma, chemotherapyBacteremiaAmikacin, Ampicillin, Aztreonam Ceftazidime, Ceftriaxone, Cefuroxime, Gentamicin, Cephalexin, Ciprofloxacin, Imipenem, Meropenem, Piperacillin/Tazobactam Tobramycin, Ticarcillin, Tetracycline,N/AIv Ciprofloxacin (10 mg/kg/day for 21 days), Amikacin (15 mg/kg/day for 21 days)Full recovery
Farshad et al., 2012 [72]2010F/19 yr oldIranOsteosarcoma, chemotherapyBacteremia, septic shockAmikacin, Ampicillin, Aztreonam Ceftazidime, Ceftriaxone, Cefuroxime, Gentamicin, Cephalexin, Ciprofloxacin, Imipenem, Meropenem, Piperacillin/Tazobactam Tobramycin, Ticarcillin, TetracyclineN/AIv Vancomycin (60 mg/kg/day for 14 days) and Imipenem (100 mg/kg/day for 14 days), then oral Ciprofloxacin (30 mg/kg/day for three weeks)Full recovery
Al Ramahi et al., 2013 [73]2013M/47 yr oldJordanRenal failure, maintained on hemodialysisBacteremiaCefepime, Ciprofloxacin, Cotrimoxzole, Levofloxacin, Ofloxacin, Polymyxin B, TigecyclineAmikacin, Gentamicin, Imipenem, Meropenem, Piperacillin/Tazobactam with intermediate sensitivity for CeftazidimeCefepime (1 g daily for 14 days), then oral Cyclosporine 200 mg twice daily, Mycophenolate Mofetil 360 mg twice daily Prednisone 30 mg twice daily, oral INH 300 mg once dailyFull recovery
Bayhan et al., 2013 [74]2013M/16 yr oldTurkeyNonePeritonitis due to perforated appendicitisAmicasin, Ampicillin, Ampicillin-Sulbactam, Ceftazidime, Cefazolin, Ciprofloxacin, Gentamicin, Imipenem, PiperacillinCeftriaxone, Cefuroxime, SXTRemoval of appendix, Saline peritoneal lavage, IV Amicasin, Ampicillin, Clindamycin (5 days)Full recovery
Altun et al., 2013 [75]2013F/29 yr oldTurkeyEnd-stage renal failure, hypertensive nephrosclerosis, CAPDPeritonitisN/AN/AIv Vancomycin, oral Ciprofloxacin (14 days)Full recovery
Orsini et al., 2014 [76]2014F/80 yr oldUSAHypertension, diabetes mellitus, hiatal hernia, osteoarthritis, cholelithiasis, obesityPolymicrobial bacteremiaCeftazidime, Carbapenems, Piperacillin/Tazobactam, SXTN/AInitially Ceftriaxone (2 g IV daily), then Nafcillin (2 g IV every 4 h), Cefazolin (1 g IV every 8 h) and Doripenem (250 mg IV every 8 h)Full recovery
Swain and Rout, 2015 [56]2015F/50 yr oldIndiaDiabetes mellitus complicated with chronic renal diseaseBacteremia, septic shockCeftazidime, Cefoperazone-Sulbactam, MeropenemAmikacin, Cefepime, Ciprofloxacin, Gentamicin, Piperacillin-TazobactamPiperacillin-Tazobactum (3.375 gm IV 6 hourly), then changed for Cefoperazone-SulbactamDied
Duran et al., 2015 [77]2015M/51 yr oldTurkeyTachycardiaEndocarditisAmikacin, Ciprofloxacin, Ceftazidime, Cefoperazone-Sulbactam, Cefepime, Colistin TigecyclineGentamicin, Imipenem, Meropenem, Netilmicin, Piperacillin-TazobactamCardiovascular surgery, CiprofloxacinFull recovery
Kim et al., 2015 [21]2015F/42 yr oldKoreaMeningioma was removed 6 days before infectionSeptic shockN/AN/AInitially Piperacillin/Tazobactam, Levofloxacin, Metronidazole iv, renal replacement therapy, Immunoglobulin IV Meropenem/Levofloxacin, then ceftazidime with levofloxacinFull recovery
Khalki et al., 2016 [78]2015N/A/18MoroccoNoneAcute appendicitisAmoxicillin—clavulanic acid, Cefoxitin, 2nd and 3rd generation Cephalosporins, Gentamycin, Amikacin, Carbapenems, Ticarcillin, PiperacillinAmino-penicillins, Aztreonam, Ciprofloxacin, Nalidixic acid, Norfloxacin, SXTSurgery, Amoxicillin-clavulanic acid IV for 48 h, then taken orally for 8 daysFull recovery
Pekintürk and Akgüneş, 2016 [79]2016M/62 yr oldTurkeyLeft hemiparesis and type II diabetesBacteremiaAmikacin, Ceftazidime, Cefepime, Ciprofloxacin, Gentamicin, Imipenem, Levofloxacin, Meropenem, Netilmicin, Piperacillin, Piperacillin-Tazobactam, Tetracycline Tigecycline, Tobramycin, SXTAztreonam, ColistinN/ADied
Parolin et al., 2016 [80]2016F/4 yr oldItalyEnd-stage renal disease, idiopathic epilepsyPeritonitisN/AN/AInitially IV Ceftazidime, Teicoplanin, then changed to Ciprofloxacin for 3 weeksFull recovery
Hung et al., 2017 [81]2017F/63 yr oldTaiwanHemodialysis patientAcute AppendicitisCeftriaxone, Ceftazidime, GentamicinCiprofloxacinCefazolin Followed by ceftriaxoneFull recovery
Ruziaki and Hashami, 2017 [82]2017F/1 yr oldOmanNoneSepsisCeftriaxone, Ceftazidime, Cefipime, Ciprofloxacin, GentamicinN/AIv Ceftriaxone (80 mg per kg per dose once a day for 14 daysFull recovery
Yasayancan and Koseoglu, 2017 [57]2017M/68 yr oldTurkeyLung cancer, adrenal metastasisPolymicrobial BacteremiaCefepime, Colistin, Levofloxacin, TigecyclineGentamycin, Imipenem, Meropenem, Piperacillin–TazobactamPiperacillin–Tazobactam and ciprofloxacin iv, then Cefepime Teicoplanin, then Tigecycline/ColistinDied
Tartar and Tartar, 2020 [83]2017M/14 yr oldTurkeyNonePerforated appendicitisAmikacin, Ampicillin–Sulbactam, Ceftazidime, Cefazolin, Ciprofloxacin, Gentamicin, Imipenem, Piperacillin, SXTN/ASurgery, IV Cefazolin (100 mg/kg), Amikacin (15 mg/kg), Metronidazole (30 mg/kg).Full recovery
Tartar and Tartar, 2020 [83]2017F/5 yr oldTurkeyNoneAcute appendicitisAmikacin, Ertapenem, Ciprofloxacin, Gentamicin, Imipenem, Piperacillin, SXTAmpicillin–Sulbactam, Ceftazidime, CefuroximeSurgery, IV Cefazolin (100 mg/kg), Amikacin (15 mg/kg), Metronidazole (30 mg/kg)Full recovery
Farooq et al., 2017
[20]
2017F/65 yr oldIndiaColostomyGastroenteritisAmikacin, Cefepime, Cefoperazone/Salbactam, Ceftazidime, Colistin, Gentamicin, Imipenem Cotrimoxazole, Minocycline, Meropenem, Piperacillin/Tazobactam, TigecyclineAztreonam, Ciprofloxacin, LevofloxacinOral Ciprofloxacin (500 mg for 3 days), probioticsFull recovery
Cetin et al., 2018 [57]2018M/10 yr oldTurkeyCerebral palsy, scoliosis, supported with long-term home mechanical ventilationPneumoniaAmikacin, Ceftazidime, Cefepime, Imipenem, Levofloxacin, Meropenem, Netilmicin, Piperacillin, Piperacillin-Tazobactam, Tigecycline, SXTAztreonam, Ciprofloxacin, Colistin, Gentamicin, TetracyclineAmikacin (1 × 225 mg), Piperacillin-Tazobactam (3 × 1.5 g) Vancomycin (4 × 150 mg),Died
Lovell and Forde, 2019 [84]2019M/39 yr oldBarbadosAlcoholism, asthma, pancreatitisBacteremiaCefepime, Cefotaxime, Ceftriaxone, Ciprofloxacin, Levofloxacin, Meropenem, Piperacillin-Tazobactam, SXTCefazolin, Ertapenem, GentamicinInitially Meropenem 1 g IV every 8 h, Fluconazole 800 mg IV, a 21-day course of Meropenem and a 14-day course of Fluconazole (unsuccessfully), then SXTFull recovery
Tiwari and Nanda, 2019 [85]2019F/46 yr oldIndiaNoneBacteremiaAmikacin, Cefuroxime, Ciprofloxacin, Colistin Gentamicin, Imipenem, Meropenem, Tigecycline, CotrimoxazolePiperacillin-TazobactamInitially Piperacillin-Tazobactam, Vancomycin, then changed for Gentamicin (4 mg/kg/daily) and Imipenem (25 mg/kg 8 hourly) for 10 daysFull recovery
Buyukberber et al., 2021 [86]2020F/4yr oldTurkeyPrevious urinary surgeryUrinary tract infectionCeftazidime, Ciprofloxacin; Meropenem Piperacillin/tazobactamAmikacin, Gentamicin, Imipenem, SXTAmikacin Followed by CeftazidimeFull recovery
Miloudi et al., 2021 [87]2020N/A/12MoroccoNoneAcute appendicitisAminoglycosides, Amoxicillin/Clavulanic acid, 2nd, and 3rd generation Cephalosporins, Carbapenems, Colistin, TicarcillinCiprofloxacin, Norfloxacin, SXTAppendectomy and surgical drainage, Amoxicillin/Clavulanic acid (3 g/24 h for 15 days)Full recovery
Ayhancı et al., 2021 [88]2021M/51 yr oldTurkeyNoneBacteriemiaAmikacin, Ciprofloxacin Gentamicin, Levofloxacin, Imipenem, MeropenemN/ALevofloxacin 500 mg/day wFull recovery
Sammoni et al., 2022 [89]2022M/16 yr oldSyriaBurn victimSepsisColistinN/ACefazolin and Ceftriaxone Followed by Colistin-amikacin for 14 daysFull recovery
F—Female, M—Male, N/A—Not Available, SXT sulfamethoxazole-Trimethoprim. * Antibiotic susceptibility testing was carried out using a variety of methods, including disk diffusion testing, agar and broth dilution testing and E-testing methods.
Table 3. Incidences of Comamonas kerstersii infection from 2013 to 2022. Main characteristics of the case reports.
Table 3. Incidences of Comamonas kerstersii infection from 2013 to 2022. Main characteristics of the case reports.
Author (Ref.)YearSex/AgeCountryCo-MorbidityType of InfectionSusceptible to *Resistance to *Antibiotic TreatmentOutcome
Almuzara et al., 2013 [90]2013F/43 yr oldArgentinaOvarian tumor with peritoneal metastasesSigmoid perforation by foreign body (biliary stent), rectovaginal fistula, and colostomyAmikacin, Ampicillin, Ampicillin-Sulbactam, Cephalothin, Cefoxitin, Cefotaxime, Ceftazidime, Cefepime, Colistin, Gentamicin, Imipenem, Meropenem, Piperacillin-Tazobactam, SXTCiprofloxacinAmpicillin-Sulbactam, Piperacillin-Tazobactam, ErtapenemFull recovery
Almuzara et al., 2013 [90]2013M/48 yr oldArgentinaNonePerforated appendixAmikacin, Ampicillin, Ampicillin-Sulbactam, Cephalothin, Cefoxitin, Cefotaxime, Ceftazidime, Cefepime, Ciprofloxacin, Colistin, Gentamicin, Imipenem, Meropenem, Piperacillin-Tazobactam, SXTN/AAmpicillin-Sulbactam, Ciprofloxacin, Amoxicillin-Clavulanic acidFull recovery
Almuzara et al., 2013 [90]2013F/10 yr oldArgentinaNonePerforated gangrenous appendixAmikacin, Ampicillin, Ampicillin-Sulbactam, Cephalothin, Cefoxitin, Cefotaxime, Ceftazidime, Cefepime, Colistin, Gentamicin, Imipenem, Meropenem, Piperacillin-Tazobactam, SXT, Ciprofloxacin, Colistin, SXTCiprofloxacinAmpicillin, Metronidazole, Gentamicin, and then Amoxicillin-Clavulanic acidFull recovery
Almuzara et al., 2013 [90]2013F/21 yr oldArgentinaNonePerforated gangrenous appendixAmikacin, Ampicillin, Ampicillin-Sulbactam, Cephalothin, Cefoxitin, Cefotaxime, Ceftazidime, Cefepime, Colistin, Gentamicin, Imipenem, Meropenem, Piperacillin-Tazobactam, SXTCiprofloxacinAmpicillin, Metronidazole, GentamicinFull recovery
Biswas et al., 2014 [91]2014M/10 yr oldUnited KingdomNonePerforated appendixAmikacin, Ceftazidime, Ciprofloxacin, Colistin, Gentamicin, Meropenem, Piperacillin-TazobactamN/AOpen appendectomy, Piperacillin-Tazobactam (5 days), Amoxicillin-Clavulanic acid, CiprofloxacinFull recovery
Biswas et al., 2014 [91]2014M/9 yr oldUnited KingdomNoneSeptic shock (due to perforated appendix)Amoxicillin-clavulanic acid, Ceftazidime, Colistin, Gentamicin, Meropenem, Piperacillin-TazobactamCiprofloxacinSurgery, Amoxicillin-Clavulanic acid, Gentamicin, Metronidazole (intravenously, 3 days), Amoxicillin-Clavulanic acid (orally)Full recovery
Opota et al., 2014 [92]2014M/65 yr oldSwitzerlandDiabetesBacteremia with sign of diverticulosisCeftazidime, Ciprofloxacin, Meropenem, Imipenem, Minocycline, Levofloxacin, SXTN/AImipenem-Cilastatin (10 days)Full recovery
Almuzara et al., 2017 [93]2017F/54 yr oldArgentinaObesity, hypertension, diabetesSeptic shockSXT, MetronidazolePiperacillin/Tazobactam, VancomycinSXT 15 mg/kg (intravenously every 12 h) and Metronidazole 500 mg (intravenously every 8 h), 30 daysFull recovery
Almuzara et al., 2017 [93]2017F/15 yr oldArgentinaNonePelvic peritonitis due to genital tract infectionN/AN/ACeftriaxone (intravenously 2 g/day, 6 days), Metronidazole (orally 500 mg/12 h, 8 days), Doxycycline (orally 100 mg/12 h, 8 days), Amoxicillin/Clavulanic acid (orally 500 mg/8 h, 14 days)Full recovery
Almuzara et al., 2018 [94]2018F/5 yr oldArgentinaNoneUrinary tract infectionAmikacin, Ampicillin, Ampicillin/Sulbactam, Cephalothin, Colistin, Cefotaxime, Ceftazidime, Cefepime, Ciprofloxacin, Gentamycin, Imipenem, Meropenem, Piperacillin-Tazobactam, SXTCeftriaxonePiperacillin/Tazobactam (intravenously 200 mg/kg per day, every 8 h, 10-days), Amoxicillin/Clavulanic (orally 50 mg/kg per day, 14 days)Full recovery
Zhou et al., 2018 [95]2018M/31 yr oldChinaNoneAcute peritonitis, perforated appendix (with abdominal abscess)All except Ciprofloxacin Levofloxacin, SXTCiprofloxacin Levofloxacin, SXTExploratory laparotomy, appendectomy, tube drainage, Cefuroxime and metronidazole (14 days)Full recovery
Liu et al., 2020 [96]2020M/62 yr oldChinaNoneIntra-abdominal infection due to perforated colonAmikacin, Ceftazidime, Cefepime, Ciprofloxacin, Colistin Imipenem, Levofloxacin, Meropenem, Minocycline, Piperacillin-Tazobactam, SXTCephalothin, Cefotaxime,
Ciprofloxacin, Gentamicin
Surgery (left thoracotomy exploration, repair of oesophageal hiatal hernia, laparotomy exploration, partial colectomy, colostomy), Piperacillin-Tazobactam (Intravenously 4.5 g, every 8 h, 14 days)Full recovery
Palacio et al., 2020 [97]2020M/16 yr oldUruguayNoneAcute appendicitisAmikacin, Ampicillin Sulbactam, Ceftazidime, Cefepime, Gentamicin, Piperacillin/Tazobactam, Meropenem, Imipenem, CotrimoxazoleN/ALaparoscopic surgery, Piperacillin/Tazobactam (intravenously, 4.5 g every 6 h, 10 days)Full recovery
Farfán-Cano et al., 2020 [98]2020M/14 yr oldEcuadorNonePerforated appendicitisN/AN/APiperacillin/Tazobactam (14 days)Full recovery
Farfán-Cano et al., 2021 [99]2020F/27 yr oldEcuadorObesity and being on lactation periodAcute appendicitisN/AN/ACiprofloxacin and Metronidazole IV for 10 daysFull recovery
Farfán-Cano et al., 2021 [99]2020M/29 yr oldEcuadorNoneAcute appendicitisN/AN/AConventional Appendectomy, Ciprofloxacin, and MetronidazoleFull recovery
Farfán-Cano et al., 2021 [99]2020M/68 yr oldEcuadorNoneAcute appendicitisN/AN/ALaparoscopic appendectomyFull recovery
Farfán-Cano et al., 2021 [99]2020F/16 yr oldEcuadorNoneAcute appendicitisN/AN/AConventional appendectomy, Ampicillin/Sulbactam + MetronidazoleFull recovery
Farfán-Cano et al., 2021 [99]2020F/16 yr oldEcuadorPsoriasisAcute appendicitisN/AN/AConventional appendectomy, Ampicillin/ SulbactamFull recovery
Rong et al., 2022 [100]2022M/82 yr oldCanadaType 2 diabetesBacteremiaCeftazidime, Gentamicin, Imipenem, Meropenem, Piperacillin/tazobactam, TobramycinCiprofloxacinPpiperacillin-tazobactam Followed by intravenous Ceftriaxone (1 g/day)Full recovery
Bennani et al., 2022 [101]2002M/8 yr oldMoroccoNoneAcute appendicitisN/AN/AIntravenous Amoxicillin-clavulanic acid, Gentamicin, and Metronidazole
Followed by oral Amoxicillin-Clavulanic acid.
Full recovery
F—Female, M—Male, N/A—Not Available, SXT sulfamethoxazole-trimethoprim. * Antibiotic susceptibility testing was carried out using a variety of methods, including disk diffusion testing, agar and broth dilution testing and E-testing methods.
Table 4. Incidences of Comamonas spp. infection from 2000 to 2022. Main characteristics of the case reports.
Table 4. Incidences of Comamonas spp. infection from 2000 to 2022. Main characteristics of the case reports.
Author (Ref.)YearSex/AgeCountryCo-MorbidityType of InfectionSusceptible to *Resistance to *Antibiotic TreatmentOutcome
Sonnenwirth, 1970 [102]1970F/71 yr oldUSARheumatic heart diseaseEndocarditisChloramphenicol,
Oxytetracycline Tetracycline
Ampicillin, Cephalothin, Colistin, Penicillin, StreptomycinPenicillinFull recovery
Isotalo et al., 2000 [103] Comamonas spp.2000M/35 yr oldCanadaNoneTenosynovitis (From an animal bite)N/AN/AIntravenous (IV) cefazolin at 1 g/8 h and gentamicin 80 mg/8 h for a total of 72 hFull recovery
Kaeuffer et al., 2018 [104] Comamonas aquatica2017M/66 yr oldFranceDiabetes, ischemic heart disease, removed sigmoid polypsBacteremia and septic shockAmoxicillin-Clavulanic acid, Ceftazidime, Cefepime, Ciprofloxacin, Imipenem, Piperacillin-TazobactamN/ANorepinephrine, Cefotaxime, Ciprofloxacin (10 days)Full recovery
Guo et al., 2021 [105] Comamonas thiooxydans2021F/60 yr oldChinaKidney stones.Urinary Tract InfectionChloramphenicol, Imipenem, SXTAmikacin, Aztreonam, Ceftazidime, Cefepime Ciprofloxacin, Gentamicin, LevofloxacinImipenem-cilastatin 1 g IV for 1 month to fightFull recovery
F—Female, M—Male, N/A—Not Available, SXT sulfamethoxazole-trimethoprim. * Antibiotic susceptibility testing was carried out using a variety of methods including disk diffusion testing, agar and broth dilution testing and E-testing methods.

6. Treatment of Comamonas spp. Infections

Antibiotic treatment of Comamonas spp. infections can be difficult. Comamonas spp. can be resistance to various antibiotic families including β-lactams (penicillins, cephalosporins and the development of resistance to carbapenems). To date, no controlled trials of antimicrobial therapies for Comamonas spp. infections in humans have taken place; consequently, antibiotic treatment ought to be based upon results of in vitro susceptibility testing on isolates. A variety of different antibiotics have been employed to treat Comamonas spp. infections found in the literature and, in most cases, they are susceptible to aminoglycosides, fluoroquinolones, carbapenems, piperacillin-tazobactam, trimethoprim-sulfamethoxazole, and cephalosporins (Table 2, Table 3 and Table 4).
Resistance to β-lactams class antimicrobials can be due to the possession of several genes by Comamonas spp. C. testosteroni S44 possesses a three-gene operon that codes for a Class A β-lactamases (resistance to benzylpenicillin, ampicillin, cefalexin, cefazolin, cefuroxime, ceftriaxone, and cefepime). These genes are CzoA (Class A β-lactamase encoding gene)—inhibits β-lactams antibiotics, CzoR (LysR type transcriptional regulator)—positively affects the expression of CzoA, and the IscR gene—enhances the regulatory effect of CzoR when bounded to its promoter region [106]. Several resistance genes were found in C. kerstersii 8943, including tetA, strB, sul1, blaOXA-1, strA, sul2, catB3 and floR. The blaIMP–8 gene (giving resistance to β-lactam antibiotics) has been found in a Comamonas thiooxydans isolate, which caused a urinary tract infection. This isolate also had a novel class D beta-lactamase gene blaOXA and a aac(6′)-Ib-c gene (resistance to aminoglycoside antibiotics). A variety of efflux pumps were also identified in the genomes of this bacterial isolate. [105]. A study in 2022 found another Comamonas thiooxydans isolate with a plasmid-based blaIMP–1 gene [107]. In a study by Hem et al., 2022, 32 Comamonas. denitrificans and 5 C. testosteroni from wastewater, 1 C. denitrificans from a wetland, and 1 C. aquatica from a lake with public access were sequenced. All were found to be resistant to carbapenem antibiotics. However, only 13 C. denitrificans isolates were found to have an identifiable carbapenemase blaGES-5. No identifiable carbapenemase genes were found in the other isolates. Other C. denitrificans isolates carried extended-spectrum b-lactamase (ESBL) blaOXA genes. This was the first report of resistance to carbapenem antibiotics in both C. denitrificans and C. aquatica; however, carbapenem-resistance was previously reported in a C. testosteroni infection in Turkey in 2015 [77,108].

7. Conclusions

Comamonas spp. are not currently considered important pathogens and are thought of as being of low virulence and of being a lesser danger in comparison to other non-fermenting Gram-negative bacteria such as Pseudomonas aeruginosa. Nevertheless, in this review, fifty-five separate outbreaks of Comamonas spp. infections have been identified from the scientific literature not taking into account unreported/undocumented cases. It must be recommended that the scientific community acknowledge the ability of this organism to elude antimicrobials and thus the potential for antimicrobial resistance transference between organisms, particularly in an era of growing antimicrobial susceptibility concerns.

Author Contributions

Conceptualization, M.P.R. methodology, M.P.R. and L.S.; investigation, M.P.R. and L.S.; data curation, M.P.R. and L.S. writing—original draft preparation, M.P.R., L.S., R.G. and S.W. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

Not applicable.

Conflicts of Interest

The authors declare no conflict of interest.

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Figure 1. Phylogenetic tree of the genus Comamonas (accession numbers are given alongside species name) with the closely related genus Delftia. The tree was built with 16S rDNA genes (partial sequences of ~1400 bp) using neighbor-joining with the Tajma-Nei method utilizing the MEGA 11 software package. Bootstrap values are represented by numbers at nodes. These are based on 1000 resamplings. Bar, 0.0050 substitutions per site [26,27]. It should be remembered that these analyses are based upon 16S rDNA and, as such, are suggestive only.
Figure 1. Phylogenetic tree of the genus Comamonas (accession numbers are given alongside species name) with the closely related genus Delftia. The tree was built with 16S rDNA genes (partial sequences of ~1400 bp) using neighbor-joining with the Tajma-Nei method utilizing the MEGA 11 software package. Bootstrap values are represented by numbers at nodes. These are based on 1000 resamplings. Bar, 0.0050 substitutions per site [26,27]. It should be remembered that these analyses are based upon 16S rDNA and, as such, are suggestive only.
Pathogens 11 01032 g001
Table 1. Listing of validly published Comamonas species.
Table 1. Listing of validly published Comamonas species.
SpeciesOrigin/Isolation SiteGenome SequencesReference
Comamonas aquaticaChina/Freshwater RiverStrain: CJG,
Size: 3.76 Mb
Ref Genome: GCA_000935165.2 (6 genomes)
Wauters et al., 2000
[28]
Comamonas aquatilisGermany/Garden PondNo GenomeKampfer et al., 2018
[29]
Comamonas badiaJapan/Activated sludgeStrain: IAM 14839, Size: 3.68 Mb
Ref Genome: GCA_000484635.1
Tago and Yokota, 2004
[30]
Comamonas compostiTaiwan/food waste compostStrain: YY287T, Size: 4.63 Mb
Ref Genome: GCA_000429845.1
(Young et al., 2008)
[31]
Comamonas denitrificansSweden/Activated sludgeStrain: 123T
Size: 3 Mb
Ref Genome:
GCA_017368815.1
Gumaelius et al., 2001
[32]
Comamonas fluminisChina/River waterStrain: CJ34T
Size: 4.86 Mb
Ref Genome:
NZ_CP066783.1
Park et al., 2022
[33]
Comamonas granuliKorea/Granules used in wastewater treatment plantStrain: NBRC 101663T,
Size: 3.51 Mb
Ref Genome: GCA_003604195.1
Kim et al., 2008
[34]
Comamonas guangdongensisChina/Subterranean Forest sedimentNo GenomeZhang et al., 2013
[35]
Comamonas humiJapan/SoilNo GenomeHatayama, 2014
[36]
Comamonas jiangduensisChina/Agricultural soilStrain: YW1T,
Size: 2.76 Mb
Ref Genome:
GCA_902829245.1
Sun et al., 2013
[37]
Comamonas kerstersiiDialysis effluent of a patientStrain: 8943,
Size: 3.55 Mb
Ref Genome:
GCA_002056725.1
Wauters et al., 2003
[28]
Comamonas koreensisKorea/WetlandStrain: YH12T,
T50-37
Size: 5.3 Mb
Ref Genome:
GCA_014076495.1
Chang et al., 2002 [38]
Comamonas nitrativoransUruguay/Denitrifying reactorStrain: 23310T, Size: 3.36 Mb
Ref Genome:
SAMN02746010
Etchebehere, 2001 [39]
Comamonas odontotermitisTaiwan/Termite Odontotermes formosanus gutStrain: Dant 3-8T, Size: 4.42 Mb.
Ref Genome:
GCA_020080045 (For WLL)
(Chou et al., 2007) [40]
Comamonas phosphatiChina/Phosphate rock powder—from phosphate mineStrain: WYH 22-41T,
Size: 4.1 Mb
Ref Genome:
GCA_014637085.1
Fuhong et al., 2016 [41]
Comamonas piscisKorea/Korean rockfish intestineStrain: CN1T,
Size: 5.2 Mb
Ref Genome:
GCA_014109725.1
Kang et al., 2016 [42]
Comamonas sediminisUSA/Lagoon sedimentsStrain: S3T,
Size: 4.42 Mb
Ref Genome: JAFBFN010000000 (for 4487)
Subhash et al., 2016 [43]
Comamonas serinivoransChina/Wheat straw compostStrain: SP-35T, Size: 4.52 Mb.
Ref Genome:
GCA_002158865.1
Daochen et al., 2014 [44]
Comamonas suwonensisRepublic of Korea/Stream waterStrain: EJ-4
Size: 4.72 Mb
Ref Genome:
GCA_012844455.2
Park et al. 2021 [45]
Comamonas terraeThailand/Agricultural soilStrain: A3-3T,
Size: 4.7Mb.
Ref Genome:
GCA_001544075.1
Chipirom et al., 2012 [46]
Comamonas terrigenaBoston/Hay infusion made from fresh waterStrain: NCIB 8193, Size: 4.7 Mb
Ref Genome:
AP019749.1
De Vos et al., 1985 [24]
Comamonas testosteroniOrganic compoundsStrain: KS 0043, Size: 5.41 Mb
GCA_000241525.2 (21 Genomes)
Tamaoka et al., 1987 [47]
Comamonas thiooxydansSulphur springStrain: S23T,
Size: 5.27 Mb
Ref Genome: GCA_000964545.1
Pandey et al., 2009 [48]
Comamonas zonglianiiChina/Phenol contaminated soilNo GenomeXin-Yan et al., 2011 [49]
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Ryan, M.P.; Sevjahova, L.; Gorman, R.; White, S. The Emergence of the Genus Comamonas as Important Opportunistic Pathogens. Pathogens 2022, 11, 1032. https://doi.org/10.3390/pathogens11091032

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Ryan MP, Sevjahova L, Gorman R, White S. The Emergence of the Genus Comamonas as Important Opportunistic Pathogens. Pathogens. 2022; 11(9):1032. https://doi.org/10.3390/pathogens11091032

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Ryan, Michael P., Ludmila Sevjahova, Rachel Gorman, and Sandra White. 2022. "The Emergence of the Genus Comamonas as Important Opportunistic Pathogens" Pathogens 11, no. 9: 1032. https://doi.org/10.3390/pathogens11091032

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