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Proteus vulgaris urinary tract infections in rats; treatment with nitrofuran derivatives.

Ascending urinary tract infections with stone formation have been produced experimentally in rats, using a modification of the method of Vermuelen & Goetz (1954a, b). A zinc disc infected with a culture of Proteus vulgaris was inserted into the bladder by suprapubic cystotomy under ether anaesthesia. The pH of the urine rises from 6.9 to 8 or 9 and calculi develop in the bladder within a few days of infection. The bladder and ureters become swollen, distended and inflamed, and renal abscesses develop. Death from renal failure generally occurs within 10 days of infection. Oral treatment with nitrofurantoin was commenced three days after infection and continued for one month. This arrested the initial rise in urine alkalinity and stone formation, and few, if any, macroscopic lesions were found at post-mortem examination. Of nine nitrofuran derivatives examined for activity against this infection several showed slight activity, but only one, N-(5-Nitrofurfurylidene)-gamma-butyric acid, was as active as nitrofurantoin when given at four times the dose, but it was also one-third as toxic. It is concluded that this technique is suitable for the examination of potential urinary antiseptics.

Animals↗

In vitro activity of cephalothin and three penicillins against Escherichia coli and Proteus species.

The susceptibility of clinical isolates of Escherichia coli (67) and Proteus species (58) to cephalothin, ampicillin, benzyl penicillin, and phenoxymethyl penicillin was determined in vitro by using broth dilution and disk diffusion tests. The data were correlated by using a four-category scheme for interpreting minimal inhibitory concentrations (groups 1 to 4) as recommended by a subcommittee of an international collaborative study of susceptibility testing. With cephalothin and ampicillin, groups 1 (susceptible) and 2 (moderately susceptible) were susceptible by the disk test, and with benzyl penicillin, similar results were observed when the interpretive zone standards were changed. Strains categorized as group 4 (very resistant) were resistant by the disk method, but group 3 (moderately resistant) strains were not adequately distinguished by disk testing. Group 3 susceptibility to benzyl and phenoxymethyl penicillins can be predicted by extrapolating results from tests with ampicillin disks.

Ampicillin↗

Serious nosocomial infection caused by Morganella morganii and Proteus mirabilis in a cardiac surgery unit.

In July and August 1981, five patients in the cardiac surgery unit of the Bristol Royal Infirmary developed septicemia caused by Morganella morganii, Proteus mirabilis, or both of these species. Three of the patients had serious wound infections, and three of the patients died. Typing of the M. morganii isolates by O-serotyping and of the P. mirabilis isolates by O-serotyping, proticine production and sensitivity, and the Dienes reaction confirmed cross infection by both species. Although M. morganii has been regarded as a relatively unimportant human pathogen in the past, it may prove to be an important cause of nosocomial infection in the future.

Adult↗

Dienes typing of Proteus strains isolated from barrier-maintained animals.

The possible use of Dienes' phenomenon for typing proteus strains as an aid to bacteriological monitoring of barrier-maintained animal units was investigated. It was rare for more than 1 Dienes' type to be isolated from an individual animal. A persistent relationship between 1 or 2 Diene's types and each strain of animal was demonstrated, although these same types were shown to be capable of causing clinical disease in their normal host. The findings suggest that Dienes' phenomenon may be of value in detecting outside contamination of barrier-maintained animals and also might usefully be applied to experimental epidemiological studies.

Animals↗

Pretreatment with colistin and Proteus sensitivity to other agents.

The effects of pretreatment with colistin (polymyxin E) on the sensitivity of Proteus mirabilis, P. vulgaris and P. morganii strains to tris and sodium deoxycholate (DOC) have been studied. Pretreatment of two P. mirabilis strains (NCTC 60 and 4199) with low concentrations (0.25 approximately 1 microgram/ml) of colistin rendered them sensitive to lysis by tris (0.05M) or DOC (250 approximately 1,000 microgram/ml) although DOC induced lysis of control (non-colistin-treated) suspensions also. In contrast, the other P. mirabilis strains, as well as the P. vulgaris and P. morganii strains were little affected by tris (0.2M) or DOC (10,000 microgram/ml) even after exposure of the cells to high colistin concentrations (up to 500 microgram/ml). Colistin-pretreated or control cells of P. mirabilis NCTC 60 rapidly lost viability when suspended in water but not when held in 0.16M sodium chloride solution. Ethylenediamine tetraacetate-pretreated cells of strains 60 and 4199 were fairly sensitive to tris, although the extent of the lysis was less than when colistin was used as pretreating agent. One strain of P. vulgaris (NCTC 4175) became sensitive to tris and to DOC following exposure of the cells to ampicillin.

Colistin↗

[Intracellular nucleodepolymerase of bacteria, representatives of the Proteus and Providencia groups. Its isolation and properties].

High activity of enzymes, splitting native, denaturated DNA, deoxyribooligonucleotides and RNA, was observed in cell free extracts of bacteria--representatives of 5 strains of Proteus-Providencia. Some properties of nucleases were studied in cell free extracts. In the bacteria studied DNAases were thermolabile proteins, which were completely inactivated at 50-60 degrees, RNAases were more thermostable. The pH optima of the DNAases were at pH 9.0-11.0 in cell free system; RNAases were maximally active at pH 8.0-9.0

Cell Fractionation↗

Combinations of antimicrobial agents: II. The in vitro sensitivity of 52 strains of proteus species to sulphafurazole, polymyxins and combinations of sulphafurazole and polymyxins.

The sensitivity of 52 strains of Proteus species to sulphafurazole, polymyxins and the combinations of sulphafurazole and polymyxins was determined by means of discs and trays. It was found that 2 and 6 strains, respectively, were sensitive to discs containing 100 mug sulphafurazole and 300 mug polymyxin B, respectively, 41 strains were sensitive to the combination of discs containing 100 mug sulphafurazole and 50 mug colistin, respectively, and 38 strains were sensitive to the combination of discs containing 100 mug sulphafurazole and 300 mug polymyxin B, respectively. The tray method proved that 2 and 5 strains were sensitive to 25 and 200 mug sulphafurazole, respectively, and that 1, 2 and 3 strains were sensitive to 25, 50 and 100 mug polymyxin B, respectively. Also 41 strains were sensitive to the combination of 100 mug sulphafurazole and 25 mug colistin and 38 strains were sensitive to the combination of 25 mug sulphafurazole and 6.3 mug polymyxin B. There was good agreement between the results of the disc and of the tray studies. The synergism between sulphonamides and polymyxins may offer therapeutic possibilities.

Drug Synergism↗

[The enterotoxigenic capacity of hemolysin-producing strains of Proteus isolated in acute intestinal infections in children].

The capacity of P. mirabilis and P. vulgaris strains isolated in acute enteric infections in children for producing enterohemolysin, a new type of hemolysin, has been shown. The relationship between the capacity of Proteus cultures for producing enterohemolysin and their capacity for inducing toxic secretory reaction on a ligated loop on the small intestine of rabbits in the absence of known thermostable and thermolabile antitoxin in bacteria.

Acute Disease↗

[Antibiotic sensitivity of the H- and O-forms of bacteria in the genus Proteus].

Proteus strains isolated from the gastro-intestinal tract of children not older than 1 year were characterized by resistance to oxytetracycline, chlortetracycline, benzylpenicillin and erythromycin. The strains were more sensitive to neomycin, monomycin and streptomycin. Antibiotic sensitivity of Pr. mirabilis and Pr. vulgaris strains increased on transfer from H- to O-form. Inverse dependence of the urease activity of the strains on their sensitivity to tetracyclines was noted.

Anti-Bacterial Agents↗

[Response to antibiotics of Proteus strains isolated from different types of clinical material].

The data on the study of the antibiotic response to 42 Proteus strains isolated from different sources in the hospitals of Kharkov are presented. The isolates belonged to P. mirabilis and P. vulgaris. Many strains were resistant to gentamicin, ampicillin and carbenicillin irrespective of the isolation source. 58.0 and 90.3 per cent of the strains isolated from patients with intestinal infections, 66.6 and 100 per cent of the strains isolated from patients with otitis, 33.3 and 66.6 per cent of the strains isolated from patients with bronchopulmonary affections and 100 and 100 per cent of the strains isolated from patients with urological diseases were resistant to gentamicin and carbenicillin, respectively. As for ampicillin, the respective figures were 74.2, 66.6, 66.6 and 100 per cent. All the strains of P. vulgaris isolated from patients with otitis, urological diseases and bronchopulmonary affections were resistant to ampicillin. The MIC of carbenicillin for all the strains except 4 indole-positive strains of P. vulgaris isolated from the faeces and bronchial excreta was much higher than the borderline values.

Ampicillin↗

[Proteus septicemias. Apropos of 4 cases].

The authors record four cases of septicemia caused by Proteus, observed at the "Hôpital Girard et Robic" resuscitation department, in Tananarive, Madagascar. The patients were young and free from visceral disorders. The first case was a post-abortum etiology with a myocardial clinical picture. The second case also was a post-abortum etiology. The course led to the septic shock and to the death. The starting point of the third case was the urinary system, following upon the removal of an urinary obstruction due to post-operative anuresis. In the fourth case, the focus was urinary with a pulmonary clinical picture. The course led to the septic shock and to the death. In all instances, the germ showed sensitivity to amikacin and to the third-generation cephalosporins. The clinical course that led to the septic shock had deeply entailed the prognosis of these septicemias.

Abortion, Septic↗

Proticine typing of serologically defined Proteus strains.

Serologically defined Proteus strains including 120 P. vulgaris, 356 P. mirabilis, 47 P. morganii, 36 P. rettgeri and 66 P. inconstans cultures isolated from a wide variety of sources, were classified by proticine (bacteriocine) typing. Using Cradock-Watson's set of indicator and producer strains, the isolates were tested for proticine production (P type) and for proticine sensitivity (S type). P. vulgaris was typable by the P method in 4.1%, by the S method in 41.6%. The respective percentages for P. mirabilis were 60.1 and 48.9. Most strains of P. morganii, P. rettgeri and P. inconstans were untypable by both methods. A correlation has been demonstrated between P/S types and certain serogroups and serotypes of P. mirabilis. It has been concluded that, in combination with the determination of O and H antigens, the P/S method of proticine typing has a high differentiating value in the epidemiological tracing of P. vulgaris and P. mirabilis.

Bacteriocins↗

[In vitro effect of cephacetril and colistin combinations on Klebsiella pneumoniae and Proteus Strains (author's transl)].

In 14 out of 43 Klebsiella pneumoniae strains (33%) the combination cephacetril-colistin showed a synergistic, in 11 strains (25%) an additive effect. In Proteus strains no synergistic action was found. The combination was more likely to be synergistic or additive in strains requiring higher minimal inhibitory concentrations of cephacetril and colistin. Most highly resistant Klebsiella pneumoniae strains were synergistically inhibited by concentrations of both drugs, which can easily be obtained in serum by usual clinical doses.

Cephacetrile↗

Alternate pathway activation of complement in a Proteus mirabilis ulceration of the cornea.

A 63-year-old patient had an extensive infiltration, ulceration, and eventual perforation of the cornea caused by Proteus mirabilis. Histopathological examination of corneal tissue that was obtained at keratoplasty disclosed that the stroma was ulcerated with a diffuse infiltration of polymorphonuclear leukocytes. Immunopathological examination of the cornea revealed prominent and diffuse staining for properdin and C3 complement. There was an absence of staining for IgG, IgA, IgM, IgE, and C4 complement. These findings suggest that the alternate pathway of complement was activated in this ulcerated cornea and that immunopathological phenomena contribute to the polymorphonuclear infiltration found with Gram-negative ulcerations of the human cornea.

Complement C3↗

Amplification of Proteus mirabilis chromosomal DNA using the polymerase chain reaction.

A Proteus mirabilis-specific polymerase chain reaction (PCR) was developed and standardized. The origin of the primers was a recombinant clone that contained P. mirabilis-specific Hind III fragment DNA of 3.5-kilobase pairs. Based on the sequence data of P. mirabilis recombinant clone, two primers designated MMKAP 1 and MMKAP 2 were synthesized for use in the PCR. A P. mirabilis-specific 3.5-kb pair DNA product was amplified by the primers from 18 strains of P. mirabilis, but not from other Protease species and bacteria. The minimum amount of target DNA detected by P. mirabilis PCR was 10 fg using ethidium bromide/ultraviolet exposure of gels or Southern blot hybridization with a P. mirabilis recombinant DNA probe.

Bacteria↗

Flagellate and non-flagellate Proteus mirabilis in the development of experimental urinary tract infection.

Three isolates of Proteus mirabilis from symptomatic human urinary tract infections (UTI) were tested for their ability to cause renal infection in mice. All three strains were fimbriated as tested by hemagglutination. One of the strains, Pr 988, did not possess flagella, whereas the other two did and were capable of swarming on solid rich media. We compared the capacity of these strains to infect mice in both the ascending and hematogenous mouse UTI models. Infection was assessed by counting viable bacteria in kidney and bladder homogenates in ascending UTI or by the presence of abscesses in the hematogenously inoculated mice. All three strains were able to infect mice in both UTI models. These results suggest that flagella are not absolutely necessary for virulence in these experimental models.

Administration, Intravesical↗