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Nosocomial infection in the community hospital: severe infection due to Serratia species.

BACKGROUND: Serratia bacteremia is an uncommon illness in hospitalized patients. The aim of this study was to determine how frequently this disease occurs nosocomially and to discover the most common portals of entry and the underlying disorders. METHODS: Fifty-six cases of Serratia bacteremia documented by blood culture (17 cases over a 4-year period in a community hospital in Gainesville, Florida, and 39 cases over a 3-year period in three community hospitals in Dayton, Ohio) were reviewed. Comparison was made with 60 control cases of general bacteremia from three Dayton hospitals. RESULTS: Of the 56 study cases of Serratia bacteremia, 45 (80.4%) were classified as nosocomial, compared with 13 (21.7%) of the controls. Twenty-seven (48.2%) of the 56 Serratia cases occurred in intensive care units. The cases were evenly distributed over the two study periods, and no outbreaks on specific units were noted. The most common portals of entry for Serratia organisms were, in descending order, lung, genitourinary tract, unknown, intravenous line, gastrointestinal tract, and skin. The most common underlying disorder for Serratia bacteremia was malignancy, followed by renal failure (acute or chronic) and diabetes mellitus. Most of the Serratia organisms tested were sensitive to carbenicillin, trimethoprim/sulfamethoxazole, ceftizoxime, ceftriaxone, ceftazidime, cefotetan, aztreonam, ticarcillin/clavulanate, and ciprofloxacin. The organisms were largely resistant to ampicillin, tetracycline, cefazolin, cephalothin, and cefuroxime. Twenty-five percent of the patients with Serratia bacteremia died, compared with 13.6 of the bacteremic controls. CONCLUSION: Serratia bacteremia is often acquired nosocomially. The mortality rate among the study population was surprisingly low for this opportunistic bacteremia, but was higher (though not significantly so) than that of the controls.

Adolescent↗

Effects of Serratia marcescens on the F1 generation of laboratory-reared Heliothis virescens (Lepidoptera: Noctuidae).

The effects of the bacterium Serratia marcescens (Bizio) was investigated on the F1 generation of laboratory-reared Heliothis virescens (F.). There was no difference in adult male or female longevity (i.e., parental generation) for individuals inoculated with S. marcescens as larvae (Serratia treatment) and those that were free of the bacterium (control treatment). However, the number of eggs laid and the prevalence of eclosion of eggs from Serratia treatment adults were reduced relative to control treatment adults. A very low number of F1 Serratia treatment eggs exhibited signs of infection, but a higher prevalence of mortality was observed for F1 larvae (n = 2,888) for the Serratia (3.5-4.6%) than for the control (1.1-1.5%) treatment. No S. marcescens was isolated from dead control larvae; whereas, 48 -54% of dead F1 larvae for the Serratia treatment were positive for the bacterium. However, there was no significant difference in larval weights between treatments. There were also no differences in either mortality or weight of F1 male pupae between treatments, but F1 female pupae were significantly smaller and prevalence of mortality was higher for the Serratia treatment. Serratia marcescens was not isolated from any of the control F1 pupae, but 6% of pupal cadavers for the Serratia treatment were positive for the bacterium. No S. marcescens was recovered from the meconia of any of the F1 adults (n = 2,600) regardless of treatment, and there were no differences in adult weights between treatments. Although sublethal effects of S. marcescens were detected, the impact and prevalence of the bacterium were tremendously reduced over the F1 generation in the absence of all but the most basic management strategies.

Animals↗

[Multiple drug resistance of Enterobacter-Serratia group isolated from clinical materials (author's transl)].

We determined the drug susceptibility of Serratia-Enterobacter group isolated from clinical materials between October 1973 and May 1974 by disk method and agar plate dilution method, and compared the drug susceptibility and multiple resistance among pigment-producing Serratia, pigment non-producing Serratia and Enterobacter. We used following drugs for susceptibility tests; ampicillin, carbenicillin, sulbenicillin, cephaloridine, streptomycin, kanamycin, dibekacin, gentamicin, chloramphenicol, tetracycline, colistin, nalidixic acid, nitrofurantoin and erythromycin. Above one half of strains of Serratia and Enterobacter was isolated from sputa and pharyngeal swabs. Almost all strains of Serratia and Enterobacter wer resistant to ampicillin, cephaloridine and erythromycin, but sensitive to gentamicin and dibekacin. Resistant strains were more found in Serratia than in Enterobacter. Pigment non-producing strains of Serratia were more sesistant to chemotherapeutics than pigment producing strains. There were many multiple resistant strains in Serratia and Enterobacter, especially in pigment non-producing strains of Serratia, and the strains isolated from urine were resistant to more drugs compared with the strains from other materials.

Ampicillin↗

L-Arabinose-ornithine-Irgasan medium for differentiating Serratia species.

A semisolid medium (designated Serratia differentiation medium) containing L-arabinose, ornithine, and selective inhibitor was used to differentiate three clinically encountered Serratia species. The inhibitor, Irgasan DP-300, was incorporated to eliminate false-positive reactions from most remaining Enterobacteriaceae. The suspected Serratia colony was inoculated as a stab into the medium. Serratia marcescens was indicated by a change in color from olive to purple following 18 h of incubation, whereas S. rubidaea (not listed in Bergey's Manual of Determinative Bacteriology) was indicated by a change to bright yellow. S. liquefaciens (described in Bergey's Manual of Determinative Bacteriology [8th ed., 1974] as Enterobacter liquefaciens) produced a small purple band at the top of the medium and a yellow or yellow-green butt. Absence of growth and color change following incubation indicates that the suspected colony is a non-Serratia. Thirty-six Serratia strains and 97 other Enterobacteriaceae and Pseudomonadaceae strains were tested. Two strains of the non-Serratia Enterobacteriaceae (one each of Citrobacter freundii and Proteus morganii) and two strains of Pseudomonas aeruginosa produced a color change in the medium. All of the Serratia strains tested were correctly identified using this medium, while 96% of the other species tested were inhibited.

Arabinose↗

A nursery outbreak caused by Serratia marcescens--scalp-vein needles as a portal of entry.

Serratia marcescens rarely causes infections in newborn infants. We recently studied an epidemic caused by a multiply-resistant, serotype 014:H12 Serratia marcescens that involved 42 infants. Cutaneous abscesses at previous intravenous infusion sites occurred nine times, usually required surgical drainage, and were the most striking infections during the outbreak. Six infants developed Serratia bacteremia and two died with Serratia meningitis; 34 patients were colonized with Serratia but remained uninfected. An epidemiologic investigation of the 83 infants at risk in the nursery assessed factors predisposing them to colonization or infection with the epidemic organism. Colonization of the throat, umbilicus, gastrointestinal tract, or skin was frequent among infants as was carriage of Serratia on nursey employees' hands. Infected and colonized infants were the most important reservoir for Serratia in the nursery and cross-infection between infants readily occurred. Scalp-vein needles appeared to provide a portal of entry of Serratia in colonized infants, predisposing them to abscess formation and bacteremia.

Cross Infection↗

Serratia: opportunistic pathogen of increasing clinical importance.

Serratia marcescens can become a formidable nosocomial (hospital acquired) pathogen, and is reported increasingly in the world literature. However, it is only a recently recognized problem in Australia. Serratia can carry an antibiotic-resistance plasmid, and, after entry of the organism into very sick patients, it may be hard or impossible to eliminate. Initial experience of Serratia in 34 consecutive cases isolated in a three-months period is presented. Rapid increase in the number of Serratia infections occurred after the appearance of a resistant strain. Urinary infection was the commonest presentation (91% of cases). The presence of an indwelling urinary catheter in a debilitated patient was the major predisposing factor. Significant bacteraemia followed in four cases with one death. Contamination of burns (surfaces) and surgical wounds was found in four cases. Serratia strains were found to be highly resistant to most antimicrobial agents in routine sensitivity testing, 20% being fully resistant to all tested agents, and nalidixic acid being the most effective inhibitor in the remainder. With bacteriocin typing of Serratia, two types were found to be dominant. These two bacteriocin types were not identified among strains isolated from other sources such as soil, water and local hospitals. Pharyngeal carriage was found in only one case, but faecal excretion of Serratia was found in 11 cases and may be a significant portal of dissemination. Cross-infection from a hospital reservoir of resistant organisms is postulated. A model of cross-infection is also proposed, and methods of control are discussed. In view of the established danger of Serratia in the hospital setting, its isolation can no longer be ignored.

Anti-Bacterial Agents↗

Clinical and microbiological survey of Serratia marcescens infection during HIV disease.

Clinical charts of 2,398 consecutive HIV-infected patients hospitalized over an 8-year period were reviewed retrospectively to identify all cases of Serratia infection and to evaluate the occurrence and outcome of these cases according to several epidemiological. clinical, and laboratory parameters. Seventeen of 2,398 (0.71%) patients developed Serratia marcescens infections: nine had septicaemia, six had pneumonia, one had a lymph node abscess, and one had cellulitis. All patients were severely immunocompromised, as evidenced by a mean CD4+ lymphocyte count of < 70 cells/microl and a frequent diagnosis of AIDS (13 patients). When compared with other disease localizations, septicaemia was related to a significantly lower CD4+ cell count and a more frequent occurrence of neutropaenia. Antibiotic, corticosteroid, or cotrimoxazole treatment was frequently carried out during the month preceding disease onset. Hospital-acquired Serratia spp. infection was more frequent than community-acquired infection and was significantly related to AIDS, neutropaenia, and sepsis. Antimicrobial sensitivity testing showed complete resistance to ampicillin and cephalothin but elevated susceptibility to ureidopenicillins, second- and third-generation cephalosporins, aminoglycosides, quinolones, and cotrimoxazole. An appropriate antimicrobial treatment attained clinical and microbiological cure in all cases, in absence of related mortality or relapses. Since only 13 episodes of HIV-associated Serratia spp. infection have been described until now in nine different reports (7 patients with pneumonia, 3 with sepsis, 1 with endophthalmitis, 1 with perifolliculitis, and 1 with cholecystitis), our series represents the largest one dealing with Serratia marcescens infection during HIV disease. Serratia marcescens may be responsible for appreciable morbidity among patients with HIV disease, especially when a low CD4 + cell count, neutropaenia, and hospitalization are present. The clinician and the microbiologist facing a severely immunocompromised HIV-infected patient with a suspected bacterial disease should consider the Serratia spp. organisms. In fact, a rapid diagnosis and an adequate and timely treatment can avoid disease relapses and mortality.

AIDS-Related Opportunistic Infections↗

Listeria monocytogenes and Serratia marcescens infections as models for Th1/Th2 immunity in laboratory cats.

Five species of bacteria known to be naturally-occurring pathogens of cats were screened for their ability to grow in feline macrophages in vitro, and to induce antibodies and delayed type hypersensitivity (DTH) responses in vivo. Two of these organisms, L. monocytogenes and S. marcescens, were selected for further study based on clear-cut differences in their in vitro and in vivo behavior. Listeria was macrophage tropic, induced DTH, and evoked poor antibody responses post-recovery, whereas Serratia remained extracellular, did not induce a DTH reaction, and produced high titer of antibodies. Young specific pathogen free cats were then inoculated subcutaneously into the drainage areas of the right and left popliteal and auricular lymph nodes with either L. monocytogenes or S. marcescens. Each of the four lymph nodes were then removed in sequence over a two week period, weighed, cultured for viable bacteria, and RNA extracted for Th1/Th2 cytokine mRNA quantitation. Antibody responses and delayed type hypersensitivity responses were also measured. Identical to pilot studies, cats infected with Serratia developed very high levels of antibody compared to Listeria infected cats but no DTH, while Listeria infected cats produced negligible or low titers of antibodies and strong DTH. Immunity to Listeria occurred around 168 h post infection as evidenced by the disappearance of living bacteria from the nodes, while immunity to Serratia took over 264 h. Pronounced lymph node hyperplasia occurred in both infections, but persisted longer for Serratia. Enlargement of Serratia infected nodes was associated with marked follicular, primary and secondary germinal center and medullary hyperplasia. Germinal center formation in Listeria stimulated nodes was much less intense and dense accumulations of macrophages dissected between follicles downward from the subcapsular sinuses. Although functional and histologic studies showed a clear-cut cell-mediated vs. humoral response in the respective Listeria and Serratia infections, preferential cytokine mRNA upregulation was observed for only two of the five major Th1/Th2 cytokines measured. Interferon-gamma, a Th1 cytokine, was much more elevated in the Listeria stimulated nodes, but TNF-alpha (also a Th1 cytokine) was more elevated in Serratia infected nodes. Interleukin-12, an important Th1 cytokine, was elevated to equal levels in both infections as were the Th2 cytokines IL-4 and IL-10.

Animals↗

Nucleotide sequences of 16S rRNA from ten Serratia species.

Comparison of 16S ribosomal ribonucleic acid (rRNA) sequences has emerged as a powerful tool for bacterial phylogeny. However, earlier studies often only included one or a few species per genus, and it is not sure whether the rRNA sequences could discriminate closely related species. The genus Serratia is composed of ten species, some being up to 60% related by DNA hybridization. The reverse transcriptase/primer extension method was used to determine 1,492 to 1,509 nucleotides in each of ten Serratia 16S rRNA sequences. All rRNA sequences determined were unique. The phylogenetic tree obtained with the neighbour-joining method showed a cluster of Serratia species distinct from both Escherichia coli and Proteus vulgaris. S. fonticola--whose position in the genus Serratia is questioned--was clearly included in the Serratia branch and grouped within the psychrophilic Serratia species. Variable regions in the Serratia rRNA molecules were identified and could serve as the basis for a specific probe design.

Base Sequence↗

On the advantage of being a dimer, a case study using the dimeric Serratia nuclease and the monomeric nuclease from Anabaena sp. strain PCC 7120.

The extracellular endonucleases from Serratia marcescens and Anabaena sp. are members of a family of nonspecific endonucleases. In contrast to the monomeric Anabaena nuclease, the Serratia nuclease is a dimer of two identical subunits. To find out whether the two active sites of the Serratia nuclease function independently of each other and what the advantage of being a dimer for this enzyme might be, we produced (i) dimers in which the two subunits were cross-linked, (ii) heterodimers consisting of a wild type and an inactive mutant subunit which were also cross-linked, and (iii) monomeric variants which are unable to dimerize. The monomeric H184R variant and the cross-linked S140C variant exhibit the same activity as the wild type enzyme, while the cross-linked heterodimer with one inactive subunit shows only half of the activity of the wild type enzyme, demonstrating functional independence of the two subunits of the Serratia nuclease. On the other hand at low enzyme and substrate concentrations dimeric forms of the Serratia nuclease are relatively more active than monomeric forms or the monomeric Anabaena nuclease in cleaving polynucleotides, not, however, oligonucleotides, which is correlated with the ability of dimeric forms of the Serratia nuclease to form large enzyme-substrate networks with high molecular weight DNA and to cleave polynucleotides in a processive manner. We conclude that in the natural habitat of Serratia marcescens where the supply of nutrients may become growth limiting the dimeric nuclease can fulfil its nutritive function more efficiently than a monomeric enzyme.

Anabaena↗

The Serratia gene cluster encoding biosynthesis of the red antibiotic, prodigiosin, shows species- and strain-dependent genome context variation.

The prodigiosin biosynthesis gene cluster (pig cluster) from two strains of Serratia (S. marcescens ATCC 274 and Serratia sp. ATCC 39006) has been cloned, sequenced and expressed in heterologous hosts. Sequence analysis of the respective pig clusters revealed 14 ORFs in S. marcescens ATCC 274 and 15 ORFs in Serratia sp. ATCC 39006. In each Serratia species, predicted gene products showed similarity to polyketide synthases (PKSs), non-ribosomal peptide synthases (NRPSs) and the Red proteins of Streptomyces coelicolor A3(2). Comparisons between the two Serratia pig clusters and the red cluster from Str. coelicolor A3(2) revealed some important differences. A modified scheme for the biosynthesis of prodigiosin, based on the pathway recently suggested for the synthesis of undecylprodigiosin, is proposed. The distribution of the pig cluster within several Serratia sp. isolates is demonstrated and the presence of cryptic clusters in some strains shown. The pig cluster of Serratia marcescens ATCC 274 is flanked by cueR and copA homologues and this configuration is demonstrated in several S. marcescens strains, whilst these genes are contiguous in strains lacking the pig cluster.

Bacterial Proteins↗

The 1.8 A crystal structure of a proteinase K-like enzyme from a psychrotroph Serratia species.

Proteins from organisms living in extreme conditions are of particular interest because of their potential for being templates for redesign of enzymes both in biotechnological and other industries. The crystal structure of a proteinase K-like enzyme from a psychrotroph Serratia species has been solved to 1.8 A. The structure has been compared with the structures of proteinase K from Tritirachium album Limber and Vibrio sp. PA44 in order to reveal structural explanations for differences in biophysical properties. The Serratia peptidase shares around 40 and 64% identity with the Tritirachium and Vibrio peptidases, respectively. The fold of the three enzymes is essentially identical, with minor exceptions in surface loops. One calcium binding site is found in the Serratia peptidase, in contrast to the Tritirachium and Vibrio peptidases which have two and three, respectively. A disulfide bridge close to the S2 site in the Serratia and Vibrio peptidases, an extensive hydrogen bond network in a tight loop close to the substrate binding site in the Serratia peptidase and different amino acid sequences in the S4 sites are expected to cause different substrate specificity in the three enzymes. The more negative surface potential of the Serratia peptidase, along with a disulfide bridge close to the S2 binding site of a substrate, is also expected to contribute to the overall lower binding affinity observed for the Serratia peptidase. Clear electron density for a tripeptide, probably a proteolysis product, was found in the S' sites of the substrate binding cleft.

Amino Acid Sequence↗

Caprylate-thallous agar medium for selectively isolating Serratia and its utility in the clinical laboratory.

A defined agar medium (hereinafter designated caprylate-thallous [CT5 agar) containing 0.01% yeast extract, 0.1% caprylic (n-octanoic) acid, and 0.025% thallous sulfate is highly selective for all Serratia species and effectively discriminates against most non-Serratia strains likely to be in the same habitats. The selectivity of CT agar is demonstrated by the very high efficiency of colony formation (mean, 80.7% of that on a nonselective complex medium) on CT agar by known Serratia strains and the very low efficiency of colony formation (close to zero) on CT agar by bacterial strains known not to be Serratia. The utility of this medium in actual clinical laboratory practice is demonstrated by the more rapid and higher recovery of Serratia on this selective medium as compared to conventional procedures of in-tandem runs of 513 consecutive urine, feces, and sputum specimens. Pigmented and nonpigmented Serratia strains deliberately added to fecal specimens can be selectively and quantitatively recovered on CT agar. CT agar compares favorably with, or in some cases is an improvement over, other selective media which have been recommended for isolating Serratia. This selective CT agar medium could be quite useful in ecological surveys, especially those related to hospital-acquired infections.

Agar↗