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Amikacin therapy of patients with multiply antibiotic-resistant Serratia marcescens infections: development of increasing resistance during therapy.

Over a recent 22 month period, 222 patients in two adjacent hospitals became infected with a multiply antibiotic-resistant strain of Serratia marcescens; 13 were bacteremic. Nineteen patients with clinically significant infections received amikacin. Nine of 11 patients with urinary tract infections were cured. In contrast, only one of eight patients with pneumonia or other deep tissue infections was cured and four died. These eight patients were severely ill; many had infections with multiple microorganisms. In four of five patients in whom the infection failed to clear promptly. Serratia strains became increasingly resistant to amikacin during therapy and these strains contributed to the death of two of these patients. Amikacin proved useful in treating patients with infections due to gentamicin-resistant S. marcescens organisms, especially urinary tract infections. However, the capacity of some strains of S. marcescens to develop resistance to amikacin may limit the usefulness of this antibiotic in the treatment of deep tissue infections which involve this microorganism.

Adult↗

Four-valve polymicrobial endocarditis caused by Pseudomonas aeruginosa and Serratia marcescens.

This report describes what is believed to be the first case of mixed Pseudomonas and Serratia endocarditis, of probable nosocomial etiology, with involvement of all four heart valves in a 56 year old nonaddicted patient. Although both organisms were recovered in culture, infection and tissue invasion were documented by light and electron microscopy. The clinical course in this patient differed from more typical patterns of Pseudomonas or Serratia endocarditis that have been observed as complications of narcotic addiction or compromised cardiac status. Our patient had the rare occurrence of endocarditis with two organisms and four-valve involvement. Clinically, however, this presented as a right-sided endocarditis and behaved as though only a single organism were present.

Endocarditis, Bacterial↗

Purification and characterization of the extracellular proteinase of Serratia marcescens.

The extracellular proteinase produced by a depressed strain of Serratia marcescens ATCC 25419 was purified and characterized. This produces more than 10-times the amount of extracellular proteinase produced by other strains of Serratia tested. The purified enzyme was prepared from the culture supernatant by (NH4)2SO4 fractionation and DEAE-cellulose chromatography. The purified enzyme has an so20,w of 3.95 and is a monomer of molecular weight 51,900. The proteinase has a broad pH optimum in the alkaline range with a maximum at pH 9.5. The enzyme will utilize a number of proteins as substrate. The products of digestion are primarily in the size range of tripeptides to hexapeptides. Peptides containing a sensitive bond and a minimum size of size amino acids are hydrolyzed. The proteinase is inhibited by chelating agents but unaffected by sulfhydryl or serine reagents and is devoid of esterase activity.

Amino Acids↗

Crystallization and preliminary crystallographic analysis of a novel nuclease from Serratia marcescens.

Crystals have been obtained of the extracellular endonuclease from the bacterial pathogen Serratia marcescens. This magnesium-dependent enzyme is equally active against single and double-stranded DNA, as well as RNA, without any apparent base preference. The Serratia nuclease is not homologous with staphylococcal nuclease, the only other broad specificity endonuclease for which a structure exists, nor is it homologous with other nucleases that have been solved by X-ray diffraction. The structure of this enzyme should, therefore, provide new information about this class of enzyme. At present we have succeeded in obtaining large, high quality crystals using ammonium sulfate. They crystallize in the orthorhombic space group P2(1)2(1)2(1), with cell dimensions a = 106.7 A, b = 74.5 A, c = 68.9 A, and diffract to beyond 2 A. Low-resolution native data sets have been recorded and a search is under way for heavy-atom derivatives.

Endodeoxyribonucleases↗

Recurrent peritonitis caused by Serratia marcescens in a diabetic patient receiving continuous ambulatory peritoneal dialysis.

A diabetic patient treated by continuous ambulatory peritoneal dialysis for end-stage renal failure had recurrent peritonitis caused by Serratia marcescens. Thirty-eight isolates of S. marcescens recovered over a 14-month period from peritoneal-dialysis effluent, catheter tips and catheter-exit sites were biotyped and serotyped. The finding that most (90%) of these isolates belonged to the same biotype and serotype suggested that the patient had relapsing infections with the same strain. Similar isolates were recovered from the peritoneal dialysates of another two patients in the same ward, neither of whom developed Serratia-associated peritonitis.

Catheters, Indwelling↗

Epidemiological study of an outbreak of Serratia marcescens in a haemodialysis unit.

Twenty-three isolates of Serratia marcescens were isolated over a 10-month period from the blood and arteriovenous shunt sites of patients undergoing haemodialysis in an artificial kidney unit. Surveillance measures performed on the equipment, sterile materials, environment and personnel of this unit yielded Serratia from the air conditioner and one of the dialysis units. The isolates from the patients and dialyser unit were pigmented and had an identical biochemical profile, antibiograms, phage typing pattern and O serotype. The isolate from the air conditioner, though of the same biotype, had a different phage and serotype. It was concluded that the dialyser was the 'common source' and that the organism was persisting in the machine in spite of recommended sterilization procedures being implemented.

Cross Infection↗

Purification and characterization of the valine sensitive acetolactate synthase from Serratia marcescens ATCC 25419.

The valine sensitive acetolactate synthase (ALS) isozyme from Serratia marcescens ATCC 25419 was purified to homogeneity. Analysis of the native molecular weight of the purified enzyme by the native pore gradient polyacrylamide gel electrophoresis indicated the molecular weight of about 178,000 and sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed the enzyme to be composed of two different types of subunits with molecular weights of 62,000 and 35,000. The molar ratio of the two polypeptides was estimated to be 1, suggesting that native enzyme is composed of two large subunits and two small subunits. The enzyme exhibits homotropic allosterism with pyruvate unlike other enteric ALS isozymes. The specificity ratio R (V[acetohydroxybutyrate]/V[acetolactate] = R.[alpha-ketobutyrate]/pyruvate]), of the enzyme was found to be 0 suggesting that the Serratia ALS has very high specificity for pyruvate. The pH optimum was around 7.5, and the enzyme was stable at 50 degrees C for 30 min. The pI value for the purified enzyme was 5.2. The concentration of branched chain amino acids for 50% inhibition of the enzyme was 0.1 mM for valine, and 1 mM for leucine and isoleucine, respectively.

Acetolactate Synthase↗

Cloning and nucleotide sequence of a flagellin-coding gene (hag) from Serratia marcescens 274.

The pigmented enterobacterium Serratia marcescens shows a high frequency of color variation. In strain 274, color variation was shown to be closely associated with flagellar variation [Paruchuri and Harshey, J. Bacteriol. 169 (1987) 61-65]. As a first step towards understanding the genetic basis of this phenomenon, we have cloned and sequenced a flagellin-coding gene of S. marcescens 274. The gene codes for a protein product of 351 aa, with a predicted Mr of 36,862. Amino acid sequence comparisons reveal a high degree of homology between the N-terminal half and C-terminal third of the Serratia flagellin and flagellins from Escherichia coli and Salmonella typhimurium.

Amino Acid Sequence↗

Functional characteristics of the recA gene from Serratia marcescens strain Sb.

The cloned recA gene from Serratia marcescens Sb was expressed and complemented defects in the UV repair, recombination, and SOS induction of an Escherichia coli host deleted for recA. Moreover, the Serratia gene, recA (Sm), supported the same frequency of recombination per unit length of DNA as did the homologous Escherichia coli gene, recA(Ec).

Cloning, Molecular↗

The cell-bound hemolysin of Serratia marcescens contributes to uropathogenicity.

The contribution of the cell-bound hemolysin of Serratia marcescens to uropathogenicity was studied in an experimental urinary tract infection in rats. The strain carrying the Serratia hemolysin colonized the urinary tract more and lead to a stronger inflammatory response compared to the isogenic hemolysin negative strain.

Animals↗

Outbreaks of Serratia marcescens infections in a cardiothoracic surgical intensive care unit.

An outbreak of infections with pigmented Serratia marcescens involving 3 patients in a cardiothoracic surgical intensive care unit is reported. A respirator is thought to have been the source of pneumonia in 2 patients, and fomite spread from 1 of these is considered responsible for the induction of fatal endocarditis in the third patient. This outbreak demonstrates the rapid dissemination of a bacterial strain within the unit, several methods of dissemination, the wide variation in apparent virulence of the organism, the alterations of antibacterial host defense which made bacterial disease possible and which determined the site of infection, and the difficulties of adequate therapy. The third patient is the seventh reported with serratia infection of a prosthetic heart valve.

Adolescent↗

Analysis of the reaction mechanism of the non-specific endonuclease of Serratia marcescens using an artificial minimal substrate.

We have studied the mechanism of action of the Serratia nuclease using deoxythymidine 3',5'-bis-(p-nitrophenyl-phosphate) as a substrate. A comparison of the activity with which the wild-type enzyme and several mutant enzymes attack this artificial substrate and herring sperm DNA, respectively, supports the suggestion that His89 is the general base and a Mg2+ ion bound to Glu127 the general acid in the mechanism of phosphodiester bond hydrolysis by the Serratia nuclease, and that Asn119 directly participates in catalysis, for example by transition state stabilisation. Arg57, Arg87 and Arg131, essential for nuclease activity, are not needed for cleavage of the artificial substrate, suggesting that they are involved in binding and positioning of nucleic acid substrates.

DNA↗

First reported successful management of Serratia marcescens bacteremia after open heart surgery in a child.

A 7 and one-half yr-old girl developed bacteremia from S. marcescens following debanding of the pulmonary artery and closure of multiple ventricular septal defects with a Dacron patch and multiple Teflon pledgets. The site of entry was probably a radial arterial catheter left in place for 8 days. Infection was eradicated by a combination of gentamicin and carbenicillin over a 4-wk period. Of 12 cases of postoperative Serratia bacteremia in adults following valve replacement, only four survived. Antibiotics of proven effectiveness against the specific isolated Serratia strain, prompt therapy sustained for 6 wk offers the prospect for cure of this serious complication of cardiac surgery.

Anti-Bacterial Agents↗

Subacute constrictive pericarditis from Serratia marcescens bacteremia.

A case report of subacute constrictive pericarditis associated with disseminated Serratia marcescens infection and bacteremia in a patient with chronic tubulointerstitial nephritis and uremia is described. Although not substantiated by clinical history, the renal pathologic features were similar to those of ethylene glycol-induced tubulointerstitial nephritis. The patient did not have a history of heroin addiction. The importance of predisposing factors such as uremia, invasive vascular procedures, tracheal intubation, peritoneal dialysis, and pericardiocentesis in Serratia infection in susceptible persons is discussed, as are possible roles of uremia, pericardiocentesis, and pericardiotomy in the pathogenesis of constrictive pericarditis in the present case.

Adult↗

Detection of Serratia outbreaks in hospital.

Infections due to Serratia marcescens were studied in 23 different hospitals. A retrospective study was done in 4 hospitals; all isolates were compared by serological typing, antibiograms, bacteriocin production, and bacteriocin sensitivity. 2 of the hospitals were having cross-infection problems due to antibiotic-resistant strains, but the other 2 had little or no cross-infection. Outbreaks were studied in 19 other hospitals. 9 of these outbreaks were classified as "common source" since contaminated "sterile solutions" were incriminated as the cause in each. One hospital had a "pseudo-outbreak," in which Serratia from E.D.T.A. blood-collecting tubes contaminated blood-cultures as they were collected. All 10 of these strains from common-source outbreaks were generally sensitive to antibiotics. Outbreaks in 9 other hospitals resulted from cross-infection and were caused by strains which were very resistant to antibiotics. Guidelines for detecting outbreaks are given and control measures are suggested.

Alabama↗

Antibiotic-sensitive Serratia marcescens infections complicating cardiopulmonary operations: contaminated disinfectant as a reservoir.

A cluster of Serratia marcescens infections complicating cardiopulmonary bypass operations was traced to contaminated quaternary ammonium disinfectant. Failure of hospital personnel to clean the disinfectant spray bottles before refilling them had enabled the organisms to survive and contaminate the environment, including the extracorporeal circulator. The organisms grew in two of four formulations of quaternary ammonium disinfectant. Serratia sensitivity to ampicillin and tetracycline was an epidemiological marker of a common-source outbreak.

Anti-Bacterial Agents↗

Peripheral sequences of the Serratia entomophila pADAP virulence-associated region.

Some strains of the Enterobacteriaceae Serratia entomophila and Serratia proteamaculans cause amber disease in the grass grub, Costelytra zealandica (Coleoptera: Scarabaeidae), an important pasture pest in New Zealand. The genes responsible for this disease reside on a large, 155-kb plasmid designated amber disease-associated plasmid (pADAP). Herein, we report the DNA sequencing of approximately 50 kb upstream and 10 kb downstream of the virulence-encoding region. Based on similarity with proteins in the current databases, and potential ribosome-binding sites, 63 potential ORFs were determined. Eleven of these ORFs belong to a type IV pilus cluster (pilL-V) and a further eight have similarities to the translated products of the plasmid transfer traH-N genes of the plasmid R64. In addition, a degenerate 785-nt direct repeat flanks a 44.7-kb region with the potential to encode three Bacillus subtilis Yee-type proteins, a fimbrial gene cluster, the sep virulence-associated genes and several remnant IS elements.

Bacillus subtilis↗

Characterisation of virulence factors of Serratia strains isolated from foods.

Out of 21 Serratia strains isolated from fresh juice and fish samples, five S. marcescens and two S. rubidaea caused lethality in mice on parenteral inoculation, but none through oral feeding. Three S. marcescens and one S. rubidaea produced heat-labile enterotoxin, detectible with the rabbit ligated ileal loop test, the mouse foot pad test and the vasopermeability factor test. Cell free culture filtrate (CFCF) of two enterotoxigenic S. mearcescens strains induced cytotoxic effect on a monolayer of Vero-cells, but CFCF of other enterotoxigenic strains could only induce cytotonic changes in Vero-cells. All strains possessed fimbriae type 3 while, only pathogenic strains had type 4 fimbriae and a colonization factor. All pathogenic Serratia strains were agglutinated at comparatively lower salt concentrations than non pathogenic strains (< 1.3 M), and had multiple drug resistance. Their public health significance is also discussed.

Animals↗