Classification, Identification, and Clinical Significance of Proteus, Providencia, and Morganella

Phenotypic Differentiation of the GeneraTable 4 shows the conventional biochemical tests necessary for the differentiation ofProteus, Providencia, and Morganella(29). All three genera are positive for phenylalanine deaminase and negative for arginine decarboxylase, malonate utilization, and acid production from dulcitol, d-sorbitol, and l-arabinose.

Current ClassificationThe genus Proteus currently consists of five named species (P. mirabilis, P. penneri, P. vulgaris, P. myxofaciens, and P. hauseri) and three unnamed genomospecies (Proteus genomospecies 4, 5, and 6).

The literature abounds with studies on the taxonomy of the genusProteus since the original publication by Hauser, who first described the genus (Table 1) (42). The termProteus means “changeability of form, as personified in the Homeric poems in Proteus … and has the gift of endless transformation” (108).

The genus originally had two species: P. mirabilis andP. vulgaris, both first described by Hauser in 1885 (42). He noted the swarming nature of the organisms and divided the strains into the two species based on the speed of their ability to liquify gelatin: P. vulgaris liquefies gelatin “rapidly,” and P. mirabilis does so “more slowly”. Hauser also described “Proteus zenkeri,” which neither swarmed nor liquefied gelatin, but he rescinded this particular finding 7 years later (43).

In 1894, Theobald Smith reported the fermentative characteristics of the two species using glucose, sucrose, and lactose and their greatly diminished or complete loss of the ability to liquefy gelatin as the culture aged (93). The previous year, he had demonstrated the unusually small amount of gas produced from glucose by P. vulgaris compared to other then-known enteric organisms.

In 1919, Wenner and Rettger in Connecticut were studying the biochemical characteristics of a larger group of Proteusstrains (108). Consistent with Hauser's work of 1885, their strains also swarmed and liquefied gelatin. All of these strains also produced hydrogen sulfide and were lactose nonfermenters. The ability to ferment glucose, sucrose, and maltose served as a means to further subdivide the strains into two groups, as Hauser had done. P. vulgaris fermented glucose, sucrose, and maltose readily, whileP. mirabilis fermented glucose readily and sucrose slowly and did not ferment maltose.

It should be noted that in 1952 Kauffmann and Edwards published a taxonomic table listing “Proteus hauseri” var.vulgaris and var. mirabilis, an alternative classification that was not long-lived (56).

In 1966, Cosenza and Podgwaite described another new species,Proteus myxofaciens, that they isolated from the larvae of the gypsy moth (19). It produces slime and is not known to have been isolated from a human. The name derives from “myxo” (Greek for slime) and “faciens” (Latin for producing).

Until the early 1960s, bacterial classification had been based primarily on cultural observations and phenotypic analysis. In 1961, Marmur described a procedure for isolating stable, biologically active, highly polymerized DNA from bacteria that was relatively free from protein and RNA (62). This was to become the first step toward molecular genetic characterization of bacteria. In 1965, Britten and Kohne developed a technique of DNA hybridization that would become the tool to resolve many of the problems in bacterial taxonomy (10a). This technique used hydroxyapatite binding for the fractionation of DNA. This process used the fact that double-stranded DNA can be cleaved to single strands and that the single strands seek to reanneal with their complementary strands. The more closely related the organisms, the more efficient the DNA-reannealing process.

After the advent of techniques such as DNA-DNA hybridization and guanine-plus-cytosine (G+C) determination, which enabled scientists to place new species into their correct genera, biochemical testing remained important but only secondarily to the results of experiments in genetic relationships. It has become clear after years of experience in determining the current taxonomic stature of human isolates that recognizing the correct classification is often a key to ascribing appropriate etiologic relationships to these strains.

In a 1978 study of 122 strains, Brenner et al., utilizing this technology, showed for the first time the genetic heterogeneity ofP. vulgaris (9). One group of strains was indole, salicin, and esculin negative and was designated P. vulgarisbiogroup 1. In 1982, Hickman et al. proposed that this group be renamedProteus penneri in honor of John Penner, the Canadian microbiologist who made many contributions to studies of the three genera of Proteeae (46).

The mid-1980s saw the advent of high-resolution polyacrylamide gel electrophoresis of proteins with computerized analysis of patterns as another taxonomic tool to identify and type bacteria (59). In 1993, Costas et al. in England used this technique to further subdivide P. vulgaris into biogroups 2, 3a, and 3b, with the type strain (NCTC 4175/ATCC 13315) being included in biogroup 3a with only one other strain (20). During the same time, O'Hara et al. in the United States, in collaboration with Grimont in France, studied many of the same strains by DNA-DNA hybridization, phenotypic characterization, and carbon source utilization. Their results paralleled those of Costas et al. and revealed that the type strain ofP. vulgaris was genetically uncharacteristic of the hundreds of strains considered typical members of P. vulgaris(C. M. O'Hara, F. W. Hickman-Brenner, A. G. Steigerwalt et al., Abstr. 94th Gen. Meet. Am. Soc. Microbiol. 1994, abstr. C-253, p. 535, 1994). In 1995, Brenner et al. requested that a neotype strain be designated for P. vulgaris (10). In 1999, this request was approved by the Judicial Commission (103). The name did not change, but a new phenotypically accurate type strain, ATCC 29905, was designated.

The studies of O'Hara et al. cited above confirmed the existence of four genomospecies within biogroup 3, which were calledProteus genomospecies 3, 4, 5, and 6. Genomospecies 3 contains only the original type strain of P. vulgaris (ATCC 13315) and one other strain. These authors have proposed that genomospecies 3 be named Proteus hauseri and that genomospecies 4, 5, and 6 remain unnamed as Proteusgenomospecies 4, 5, and 6, respectively (71). Proteus hauseri would honor Gustav Hauser, the German microbiologist, who first described the genus. The respective Proteus type strains are listed in Table 5.

16S rRNA ClassificationIn the early 1980s, sequencing of 16S rRNA genes with subsequent comparison of these sequences and phylogenetic analysis became another promising taxonomic tool. The 16S rRNA gene of three strains ofP. vulgaris (GenBank file names PVU233425 [95], PRMRRD [13a], and PVRN16S [direct submission]) have been completely sequenced, but extensive studies have not been completed that would prove other taxonomic relationships.

Typing SystemsTyping systems for the Proteeae include phage, bacteriocin, protein profile, serological, restriction fragment length polymorphisms, and PCR. Because these systems are not routinely used in clinical laboratory work, they will not be discussed in this review. Senior reviewed all of these systems for the three genera in 1998 (87).

Clinical Significance Proteeae are widespread in the environment and make up part of the normal flora of the human gastrointestinal tract. AlthoughEscherichia coli accounts for the largest percentage of cases of uncomplicated cystitis, pyelonephritis, and prostatitis,Proteus ranks third as the cause of these infections, particularly in hospital-acquired cases (96). P. mirabilis accounts for approximately 3% of nosocomial infections in the United States (15) and is commonly isolated in clinical microbiology laboratories.

In a study by Müller, P. mirabilis and P. penneri were isolated significantly more often from stools of patients with diarrheal disease than from healthy patients, leading him to speculate that these species may play a role in some diarrheal disease (68). Their true role, however, remains unsubstantiated.

P. mirabilis has been implicated in bacteremia (3, 106), neonatal meningoencephalitis (39), empyema (49), and osteomyelitis (63). P. penneri has been implicated in a case of bacteremia and concomitant subcutaneous thigh abscess in a neutropenic patient with acute lymphocytic leukemia (23) and in nosocomial urosepsis in a diabetic patient from whom the organism was also subsequently isolated from bronchoalveolar lavage fluid and a pulmonary artery catheter tip (60). The urease enzyme of P. penneri is also believed to be a leading cause of kidney stone formation (40); indeed, the organism has been isolated from the center of a stone removed from a patient with persistent P. penneri bacteriuria (57). P. penneri has also been isolated from stool and infected conjunctiva.

Nosocomial transmission, while uncommon, has been reported. In 1983, Williams et al. reported on five patients in a cardiac surgery unit with septicemia caused by either P. mirabilis,Morganella morganii, or both organisms (109). No environmental source was identified, although O serotyping confirmed cross-infection of patients by both species. Other reports have included an outbreak of neonatal meningoencephalitis (92), infections in a hospital newborn nursery traced to a single nurse (12), and an outbreak in a surgical intensive care unit spread either by autoinfection or gastrointestinal colonization prior to cross-infection (16). In a review of 27 cases in Toronto, Canada, in 1987, Krajden et al. reported the isolation of P. penneri from urine, abdominal, neck, groin, and hip wounds, conjunctiva, sacral decubitus, and sputum (58). All of these infections were hospital-acquired infections. The report by Burke et al. also reviewed other cases where P. mirabilis was incriminated as the cause of hospital-acquired infections (12).

In a very unusual case reported by Engstrand et al., a patient withP. mirabilis bacteremia was shown to have contaminated a unit of platelet concentrate (24). This is in direct contrast to the chain of events which normally occurs in which blood or platelet concentrate is contaminated and the patient suffers a transfusion-transmitted bacteremia. Arbitrarily primed PCR typing was used to confirm identical patterns in strains from both the patient and the platelet concentrate.

In the last 10 years, there has been a report in the literature to suggest that P. mirabilis may play an etiopathogenic role in rheumatoid arthritis (110). This study showed that patients with rheumatoid arthritis have higher levels of urinaryProteus than do comparable healthy controls of either sex or women with non-rheumatoid-arthritis arthritic conditions, findings which are disputed by another group (63b), perhaps due to a difference in the methods used in their studies.

Antimicrobial SusceptibilityThe indole-negative P. mirabilis strains are generally more susceptible to antimicrobials than are P. vulgaris,P. penneri, and P. hauseri. P. mirabilis has intrinsic resistance to nitrofurantoin and tetracycline but is generally susceptible to the amino- and ureido-penicillins (ampicillin, amoxicillin, and piperacillin), cephalosporins (cefazolin, cefoxitin, cefuroxime, cefotaxime, ceftazidime, ceftriaxone, ceftizoxime, and cefepime), aminoglycosides (amikacin, gentamicin, and tobramycin), imipenem, ciprofloxacin, and trimethoprim-sulfamethoxazole (34, 82, 101, 112). However, high levels of ciprofloxacin resistance have been reported for P. mirabilis and Providencia spp. in hospitals where use of this agent is unrestricted (100). The intrinsic resistance to tetracycline can be used as an identification marker for this organism.

In 1979, Chow et al. reported an outbreak of P. mirabilisthat was resistant to ampicillin, cephalothin, tetracycline, chloramphenicol, carbenicillin, colistin, trimethoprim-sulfamethoxazole, streptomycin, and the aminoglycosides (16). An outbreak of P. mirabilis that was resistant to both gentamicin and the antiseptic chlorhexidine, as well as seven other antimicrobial agents, was reported as the cause of urinary tract infections in 90 patients in England in 1987 (21). The source of the outbreak was linked to the introduction of a catheter care policy involving chlorhexidine.

In an unusual outbreak in a hospital nursery, the strain of P. mirabilis that was responsible for bacteremias and meningitis in newborns was tetracycline susceptible. This very unusual antimicrobial pattern was used as a marker to trace the epidemiology (12).

P. penneri is generally more resistant to penicillin than isP. vulgaris, and its susceptibility pattern more closely reflects that of M. morganii than that of P. vulgaris. These Proteeae are generally susceptible to cefoxitin, broad-spectrum cephalosporins (cefotaxime, ceftriaxone, ceftizoxime, and ceftazidime), cefepime, aztreonam, aminoglycosides, ciprofloxacin, tazobactam, and imipenem (34, 112) and may be resistant to cefazolin, cefprozil, cefuroxime, cefamandol, cefdinir, cefoperazone, loracarbef, ampicillin, and the ureidopenicillins (5).

In a 1996 study, Fuchs et al. reported that the discrepancy between disk diffusion testing and broth microdilution testing for P. vulgaris was noteworthy (34). In that study, 100% of 25 P. vulgaris isolates were susceptible to four broad-spectrum cephalosporins by disk diffusion but only 64 and 40% were susceptible to cefotaxime and ceftriaxone, respectively, by broth microdilution. Laboratorians should be aware of this possible discrepancy in testing and should evaluate the results conservatively.

Current ClassificationThe genus Providencia consists of five species:P. alcalifaciens, P. heimbachae, P. rettgeri, P. rustigianii, and P. stuartii.

In 1904, Rettger isolated a previously undescribed organism from chickens during an epidemic resembling fowl cholera, but he did not submit the isolate to detailed study until 14 years later, when it was further characterized and named Bacterium rettgerei by Hadley et al. (Table 2) (41).

In 1920, Ornstein described an organism that he named Bacillus inconstans (75). This strain was isolated from the human intestine and would later be determined to be the first description of a strain of the genus Providencia. Over the years, many literature references, including Shaw and Clarke (88), have cited Ornstein's work as having been published in 1921. However, the original publication, as well as the 1921 edition of Index Medicus (36), has revealed that this work was actually published in 1920.

In 1941, Rustigian and Stuart studied a strain designated 33111 and learned that it attacked urea readily (83). The next year, Cope and Kilander published a study on a group of 83 “atypical” organisms that were biochemically similar to “Shigella paradysenteriae” Flexner but were antigenically distinct from the well-recognized types of Shigella (17). In 1943, Stuart et al., in a collaboration with Cope, realized that both of their laboratories were studying the same organism, whose strains then numbered 48, and that those organisms were clearly members of the genus Proteus (98). These strains were positive for both urea and indole, as were the strains of Shigella rettgeri studied by St. John-Brooks 20 years earlier (97). Neter in 1942 had already suggested that “S. rettgeri” be eliminated from the genus Shigella(70), a suggestion that now had sufficient justification. Rustigian and Stuart recommended that these strains be redescribed asProteus rettgeri, even though, unlike otherProteeae, they were positive for d-mannitol fermentation (84).

Changes were also taking place in the classification of a similar group of organisms being referred to as “anaerogenic paracolon 29911” (98). In 1943, Stuart had initially studied 23 of these strains, which were not Proteeae because there were no homologous reactions with Proteus antisera. The following year, Gomes described “Eberthella alcalifaciens” (38), which would later become the type species ofProvidencia. In 1951, Kauffmann designated the anaerogenic paracolon 29911 strains of Stuart (1943) as the Providence group because Stuart worked at Brown University in Providence, R.I. (53). Kauffmann showed that the only reliable difference between these Providence strains and those in the genusProteus was the inability of the Providence strains to decompose urea. An additional 35 strains of the Providence group isolated from urine specimens were described by Brooke in 1951 (11). By 1952, Kauffmann and Edwards had assigned the genusProvidencia to this group, with the species beingprovidenciae (56).

The years 1952 to 1962 saw a lot of taxonomic instability involving this genus. In another proposal in 1953, Kauffmann created a separate genus for Proteus rettgeri that was called “Rettgerella” (54). He reversed this opinion in 1954 (55).

In 1954, Singer and Bar-Chay suggested (92) and Buttiaux et al. proposed (13) that the Providence group of Stuart be placed into the genus Proteus as Proteus stuartii, because their physiological characteristic of smell as well as their biochemical characteristics were so similar to those ofProteus rettgeri. Singer also established that transformation of phenylalanine into phenylpyruvic acid was a valuable differential test for the separation of theProteus-Providence group, which are positive in this test, from other members of the Enterobacteriaceae, all of which were thought at this time to be negative in this test.

Ewing et al., also in 1954, further subdivided the Providence group into two biochemical groups designated 1 and 2 based on the production of gas from glucose as well as the fermentation patterns in adonitol and inositol (28). They also reported that the Providence strains appeared to be an intermediate group between Proteus morganii and Proteus rettgeri but differed from theProteus species based on their failure to utilize urea.

During 1955, Shaw and Clarke, utilizing additional biochemical tests, were able to reinforce the relationship of the Providence group of cultures to those within the genus Proteus. They wrote that the first reported description of a Providence culture appeared to be that of “Bacillus inconstans” Ornstein 1920, so that the type species of the Providence isolates should actually beProteus inconstans (88). In the same journal that month, Proom made a valid argument against including both the Providence group and strains of P. rettgeri in the genusProteus since several of their biochemical characteristics were dissimilar from those of other members of the genus. His alternative was to establish a new genus to include the Providence group and Proteus rettgeri isolates (79).

In what might be considered landmark papers in 1958 and 1962, Ewing reviewed the taxonomy of the Proteeae (25, 26). He agreed that the Providence group could not be incorporated into the genus Proteus and stated that the correct generic term for the Providence group should be Providencia and the proper species name would be Providencia inconstans. However, he further contended that there was insufficient evidence to either exclude Proteus rettgeri from the genus Proteusor create this new genus to contain only the Providence group andProteus rettgeri. He also proposed that the existing genusMorganella, first proposed in 1943 (35), might include the species morganii, rettgeri, andinconstans. Apparently this proposal was never acted upon by the Judicial Commission.

In the 1962 report, Ewing regarded the specific epithet “providenciae” as invalid, since the species was neither defined nor characterized (26). However, an original culture of Eberthella alcalifaciens de Salles Gomes 1944 was available that had been defined, characterized, and validly published (38). Phenotypically, E. alcalifaciens had been shown to closely resemble the description of the Providenciastrains. Ewing was satisfied that the phenotypic characteristics were similar enough to recommend that the type species forProvidencia should be Providencia alcalifaciens. As a result of continued work, Providencia subgroups A and B of Ewing could now be even more clearly divided. Subgroup A becameP. alcalifaciens, and subgroup B became P. stuartii (26). Ten years later, in 1972, Ewing et al. delineated four biogroups of P. alcalifaciens and two biogroups of P. stuartii based on the production of gas from glucose and the production of acid from adonitol and inositol (27).

The ability of Proteus rettgeri to produce acid from salicin, l-rhamnose, d-mannitol, adonitol,d-arabitol, and erythritol formed the basis used by Penner et al. in 1975 to divide these strains into five biogroups (77). Two years later, Farmer et al. (30) proposed that P. rettgeri biogroup 5 be reclassified asProvidencia stuartii urea positive.

In a 1978 study, Brenner et al. reclassified several organisms based on DNA-DNA hybridization (9). Proteus rettgeribecame Providencia rettgeri, and the assignment ofProteus rettgeri biogroup 5 to the genusProvidencia as P. stuartii was confirmed.

DNA hybridization in 1983 resulted in P. alcalifaciensbiogroup 3 being named Providencia rustigianii to honor Robert Rustigian, who did early studies on the Proteus group (48). This report also confirmed that P. alcalifaciens biogroup 4 was the same as P. stuartii. The four species of Providencia could now be separated by their ability to hydrolyze urea and produce acid fromi-inositol, adonitol, d-arabitol, trehalose, andd-galactose. Later that same year, Müller, working independently in Germany, published a report describingProvidencia friedericiana, which was isolated from fecal specimens of five varieties of penguins (67). Three years later, DNA hybridization studies would prove that P. friedericiana and P. rustigianii were identical, and the name P. rustigianii would be given priority overP. friedericiana because it was published and validated first (47). Coincidentally, in 1986, Müller et al. described another new species, Providencia heimbachae, also isolated from the feces of penguins (69). This specific name was selected to honor Friederike Heimbach, who isolated 12 of the original strains.

In 1987, Owen et al. confirmed the G+C content of the type strains ofProvidencia and reported that the genus had a narrow and homogenous range of 39 to 43 mol% (76). Table 5 lists the respective type strains for the Providencia genera.

16S rRNA ClassificationTo date, no sequencing of the 16S rRNA genes ofProvidencia has been reported or deposited.

Clinical SignificanceHuman isolates of Providencia species have been recovered from urine, throat, perineum, axilla, stool, blood, and wound specimens. P. heimbachae and P. rustigianii have also been isolated from penguins (48, 69).

When Gomes first described Eberthella (nowProvidencia) alcalifaciens in 1944, the strain with which he worked was isolated from an 11-month-old child with dysentery (38). Haynes and Hawkey found a higher incidence of P. alcalifaciens in patients with diarrhea than in healthy patients and suggested that this organism may be a cause of diarrhea, particularly in children (44). Albert et al. have shown that P. alcalifaciens is capable of invading HEp-2 monolayers in rabbits, but the relevance to human disease is not clear (1).

P. stuartii has long been recognized as a pathogen for nursing home patients with chronic indwelling urinary catheters. A total of 21 to 61% of urinary tract specimens in this population contain either P. mirabilis or P. stuartii, and the organisms may even result in a fatal bacteremia (105).

There have been rare incidents of P. rettgeri causing nosocomial infections. Traub et al. reported an outbreak of urinary tract infections caused by a highly resistant lactose-fermenting strain of P. rettgeri (102). While the organism was easily traceable because of this unusual biochemical characteristic, no common source of the outbreak was discovered. In a similar report, 10 patients had urinary tract infections caused by a highly resistant strain of P. rettgeri, and one death was believed to have been caused by these infections (22). The spread of infection was probably by contact with hospital personnel; the outbreak ended after the use of disposable gloves and contact isolation procedures were implemented. Other similar problems have been reported in the literature (61).

Antimicrobial Susceptibility P. rettgeri and P. stuartii are generally resistant to gentamicin and tobramycin but susceptible to amikacin. Urine isolates are susceptible to the expanded-spectrum oral cephalosporins, including cefaclor, cefuroxime, cefetamet, cefpodoxime, ciprofloxacin, and amoxicillin-clavulanic acid (18).Providencia spp. are also susceptible to thienamycin, ceftazidime, cefotaxime, ceftizoxime, and moxalactam. Alternative choices for antimicrobial therapy would include ceftriaxone, mezlocillin, imipenem, and trimethoprim-sulfamethoxazole (94).

In a continuous monitoring study of imipenem and ciprofloxacin use with nonfastidious clinical isolates, Fass et al. reported that the susceptibility of P. stuartii to ciprofloxacin decreased from 100 to 46% over a 6-year period in their institution, illustrating the potential for emerging resistance in this group and the need for routine susceptibility tests (31). Virtually all Morganella spp., Proteus vulgaris,Proteus penneri, and Providencia strains are capable of producing inducible β-lactamases that will hydrolyze primary and extended-spectrum penicillins and cephalosporins (99). For these reasons, the susceptibility ofProvidencia isolates needs to be monitored and specialized testing may be required.

A hospital-acquired outbreak of multiply resistant P. rettgeri occurred in 1976 and involved 127 patients over a 22-month period in Tennessee (52). These strains were resistant by disk diffusion to 15 antimicrobials and by broth microdilution to 3 antimicrobials. Exposure to multiple antimicrobials coupled with simultaneous gentamicin administration, polymyxin-neomycin bladder irrigation, or indwelling urinary tract devices predisposed the patients to infections with resistant strains.

Current ClassificationThe genus Morganella currently consists of one species,Morganella morganii, with two subspecies,morganii and sibonii.

During 1905, Castellani described a bacterium that he isolated from a human case of “fever” similar to typhoid fever. In 1914, he studied this isolate plus two additional identical strains. He called these “Bacterium columbense” after Colombo, the city in Ceylon where he worked, and noted that they were probably neither the paracolon nor paratyphosus D bacteria reported by other workers (Table3) (14). Many years later, these strains would be classified by Fulton into the genus Morganella (35).

In 1906, while studying the etiology of summer infantile diarrhea, Morgan described a non-lactose-fermenting organism that was completely different from the Flexner type of “Bacillus dysenteriae” that was implicated as the cause of the pediatric disease then occurring in the Phillipines, Germany, and the United States (66). This organism was to become known as Morgan's bacillus and in 1919 would be named “Bacillus morganii” by Winslow et al. (111). It was positive in tests for indole production and the fermentation of carbohydrates but negative for the liquefaction of gelatin.

Seventeen years after Winslow had named Morgan's bacillus “Bacillus morganii,” Rauss performed more extensive experiments on this group of bacteria (80). His work showed that these strains exhibited a spreading phenomenon, which he called emanation, and although it was less marked than that exhibited byProteus, it made these strains, in his mind, definitely part of the Proteus group. Indeed, in the fifth edition ofBergey's Manual of Determinative Bacteriology, published in 1939, this organism was called Proteus morganii(4).

A major development that occurred in 1943 was the work by Fulton, which showed that “Bacterium columbense”Castellani 1914 was actually the same organism as Proteus morganii Winslow 1919. He proposed the genus name Morganella for these strains, which were negative for the fermentation of lactose or sucrose but produced indole (35). The type species would be M. morganii Morgan 1906, with an additional species, “M. columbensis.”

In a review article in 1962, Ewing reported that the isolate of “Bacterium columbense” Castellani had been reidentified as Escherichia coli (26), thus negating this organism from the genus Morganella in which it had been placed by Fulton in 1943. This deletion would have resulted in M. morganii being the only species remaining in the valid genusMorganella. Therefore, the species morganii was relegated to the genus Proteus for another 16 years.

Since 1976, it has been known that trehalose fermentation could divide the genus into more than one biogroup (89). Studies by Hickman et al. in 1980 suggested that positive lysine and ornithine decarboxylase reactions correlated with additional divisions with the genus (45). In their 1978 study, Brenner et al. confirmed the assignment of P. morganii to the genusMorganella based on DNA-DNA hybridization (9). In 1985, Farmer et al. proposed that the nonmotile members of Hickman's lysine-positive group be designated M. morganii biogroup 1 (29).

In an extensive study of these groups in 1992, also based on DNA hybridization, Jensen et al. defined two subspecies containing four and three biogroups, as shown in Table 8 (50). M. morganii subsp. morganii contains four biogroups. Biogroup A contains the type strain of the species (ATCC 25830). Biogroup B is the previous biogroup 1 of Farmer.

The type strains for the two subspecies of Morganella are listed in Table 5.

16S rRNA ClassificationTo date, no sequencing of the 16S rRNA genes of the genusMorganella has been performed.

Clinical Significance M. morganii is an opportunistic secondary invader that was originally thought to be the cause of summer diarrhea (66). In 1986, Müller isolated M. morganiisignificantly more often from patients with gastrointestinal disease than from healthy controls (68). Case reports implicating this organism as a cause of disease, although rare, are scattered throughout the literature. For example, M. morganii has caused neonatal sepsis in an 11-day-old boy (85), a brain abscess in a neonate (104a), and a tubo-ovarian abscess (originally mistaken for vasculitis attributed to Henoch-Schonlein purpura) in a 15-year-old girl (78). Reports involvingM. morganii infections in immunocompromised individuals include chorioamnionitis and neonatal seizures in a pregnant woman (51), a postoperative foot infection in a diabetic (37), and pyomyositis (1a) and meningitis (63a) in AIDS patients. Schonwetter and Orson also described a case of atypical pyoarthritis due to M. morganii in an elderly patient (86). This case was atypical in that it had a very benign clinical presentation with minimal inflammatory response over a prolonged period. Sica et al. reported a patient with acute lymphoblastic leukemia who underwent a resolvent splenectomy for immune pancytopenia following an allogeneic bone marrow transplant (90). The patient developed pericarditis, from whichM. morganii was isolated. The authors conclude that splenectomy could have been a predisposing factor for the development of this unusual complication.

One report of nosocomial infections with M. morganiiinvolved three cases of septicemia in a cardiac surgery unit, for which no common source was discovered. Two of the three cases patients a polymicrobic infection including P. mirabilis. Two of the three cases were fatal (109). Another report described 13M. morganii infections scattered over four services and five floors of a hospital; this outbreak was eventually resolved when strict aseptic techniques, i.e., hand washing, were reinforced (104).

Additional human sources from which the organism has been isolated include urine, gallbladder, stool, sputum and other respiratory samples, and assorted wound sites.

Antimicrobial Susceptibility M. morganii is susceptible to many of the currently used antimicrobial agents, including ceftazidime, cefepime, aztreonam, imipenem, tazobactam, ciprofloxacin, tobramycin, and gentamicin. Strains are often resistant to the newer cephalosporins, including cefprozil, cefuroxime, loracarbef, cefdinir, and cefetamet (7). They can also be resistant to cefazolin, cefixime, cefpodoxime, and ampicillin.

As with strains of Providencia spp., Morganellaspp. are capable of producing β-lactamases. When automated susceptibility testing is performed on these organisms, a 3- to 6-h time frame may not be adequate for expression of all of the bacterial resistance mechanisms and could result in a report of false susceptibility (32). False resistance also may occur in testing with aztreonam because elongation of cells just before lysis can be interpreted by the instrument as growth (6). York et al. reported on the inability of the MicroScan Walk/Away rapid susceptibility panels to detect resistance to expanded- and broad-spectrum cephalosporins with some Morganella and indole-positive Proteus isolates (113). Laboratorians must monitor susceptibility results involving these antimicrobials when using commercial systems.