Nosocomial outbreaks caused by Leuconostoc mesenteroides subsp. mesentoroides.From July 2003 through October 2004, 42 patients became infected by strains of Leuconostoc mesenteroides Leuconostoc mesenteroides is a species of bacteria sometimes associated with fermentation, under conditions of salinity and low temperatures. See also
Nutrition supplied intravenously, thus bypassing the patient's digestive tract entirely. Mentioned in: Electrolyte Supplements, Necrotizing Enterocolitis parenteral nutrition was the likely source. ********** Leuconostoc species are catalase-negative, gram-positive microorganisms with coccoid coccoid resembling a coccus. morphology (1). In 1985, Buu-Hoi et al. (2) reported the first cases of Leuconostoc infection in humans. Since then, Leuconostoc spp. have been implicated im·pli·cate tr.v. im·pli·cat·ed, im·pli·cat·ing, im·pli·cates 1. To involve or connect intimately or incriminatingly: evidence that implicates others in the plot. 2. in a variety of infections (3-8), particularly in patients being treated with vancomycin vancomycin (văn'kōmī`sĭn), antibiotic resembling penicillin in the way it acts. It is derived from the bacterium Streptomyces orientalis, which was isolated from soil of India and Indonesia. and in immunocompromised immunocompromised /im·mu·no·com·pro·mised/ (-kom´pro-mizd) having the immune response attenuated by administration of immunosuppressive drugs, by irradiation, by malnutrition, or by certain disease processes (e.g., cancer). patients. However, these species have never previously been considered as agents that cause severe hospital outbreaks that threaten the lives of large numbers of persons. Between July 2003 and October 2004, and between August and November 2006, 42 and 6 patients, respectively (Figure 1), in the Juan Canalejo Hospital (a tertiary-level, 1,400-bed hospital serving a population of 516,000 in La Coruna La Co·ru·ña A city of northwest Spain on the Atlantic Ocean west of Oviedo. Perhaps predating Roman times, it was the point of departure for the Spanish Armada (1588). Population: 224,000. , northwest Spain) became infected by a strain of Leuconostoc mesenteroides subsp, mesenteroides (LM). The patients had been admitted to 13 different, physically separated departments in the hospital (3 different hospital buildings), and 11 of the 48 were newborns. The aims of the present study were to characterize the epidemiologic features of the outbreak and to determine the risk factors associated with the infection. The Study All bacterial isolates related to the outbreaks (1 per patient) were obtained from clinical samples. The strains were identified phenotypically by rapid ID 32 STREP (bioMerieux, Marcy l'Etoile, France), which yielded profile 22025001100 (Leuconostoc spp. 99.9%) and BIOLOG GP2 panels (Biolog, Hayward, CA, USA) (98%, T = 0.708). The results were confirmed by 16S rDNA sequence analysis, by a previously reported method (9), and the analysis of 1,420 1,500 bp showed 99% probability that the species were LM, when compared with GenBank database sequences. Antimicrobial drug susceptibility was determined by microdilution, with DadeMicroscan system (Baxter Health Care, West Sacramento, CA, USA), and MICs were confirmed by E-test (AB Biodisk, Solna, Sweden). For interpretation of antimicrobial drug susceptibility, Clinical and Laboratory Standards Insitute criteria (10) for Leuconostoc spp. or when appropriate Streptococcus streptococcus (strĕp'təkŏk`əs), any of a group of gram-positive bacteria, genus Streptococcus, some of which cause disease. spp. other than S. pneumoniae, were used. The antimicrobial drug susceptibility profiles were almost identical for all genotypes and showed susceptibility to penicillin and gentamicin gentamicin /gen·ta·mi·cin/ (jen?tah-mi´sin) an aminoglycoside antibiotic complex isolated from bacteria of the genus Micromonospora, (MICs of 0.25 mg/L and <2 mg/L, respectively) and to levofloxacin, tetracycline tetracycline (tĕ'trəsī`klēn), any of a group of antibiotics produced by bacteria of the genus Streptomyces. They are effective against a wide range of Gram positive and Gram negative bacteria, interfering with protein , quinupristin-dalfopristin, linezolid, daptomycin, erythromycin erythromycin (ĭrĭth'rōmī`sĭn), any of several related antibiotic drugs produced by bacteria of the genus Streptomyces (see antibiotic). , clindamycin, and chloramphenicol chloramphenicol (klōr'ămfĕn`əkŏl'), antibiotic effective against a wide range of gram-negative and gram-positive bacteria (see Gram's stain). It was originally isolated from a species of Streptomyces bacteria. . A pulsed-field gel electrophoresis gel electrophoresis n. Electrophoresis performed in a gel composed of agarose, polyacrylamide, or starch. (PFGE PFGE Pulsed-Field Gel Electrophoresis ) technique was used to assess the possibility of a clonal relationship among the 48 LM strains. Genomic DNA genomic DNA n. The full complement of DNA contained in the genome of a cell or organism. was extracted, restricted with ApaI, and electrophoresed with CHEF-DRIII apparatus (Bio-Rad Laboratories, Richmond, CA, USA). The isolates were classified epidemiologically, according to according to prep. 1. As stated or indicated by; on the authority of: according to historians. 2. In keeping with: according to instructions. 3. published criteria (11). No differences in the band profile were observed among the 42 strains of the first outbreak (genotype 1). Analysis of the 6 strains isolated in the 2006 outbreak showed different DNA DNA: see nucleic acid. DNA or deoxyribonucleic acid One of two types of nucleic acid (the other is RNA); a complex organic compound found in all living cells and many viruses. It is the chemical substance of genes. band patterns from those corresponding to genotype 1 (Figure 2). Of the 6 isolates, 4 shared the same genotype, designated genotype 2, whereas the remaining 2 isolates showed 2 new genotypes (genotypes 3 and 4). One LM strain, isolated from the parenteral nutrition catheter of a patient involved in the 2006 outbreak (genotype 2), was identical to those isolated from blood of the same patient (Figure 2) and from 3 other patients involved in the 2006 outbreak (data not shown). Most of the 42 patients infected with LM genotype 1 in the first outbreak displayed severe underlying diseases (Table 1); 9 of the patients died, and 3 of the deaths (7.1%) were directly related to the Leuconostoc infection. The bacterial isolates were isolated from blood (52.1%), catheter (21.8%), or both (26.1%). To assess risk factors related to acquisition of LM strains, we performed a case--control study. The first 42 patients (2003-2004) were designated as case-patients. Control-patients (n = 61) were randomly selected among remaining patients with another nosocomial infection Nosocomial infection An infection that can be acquired in a hospital. ABPA is a nosocomial infection. Mentioned in: Allergic Bronchopulmonary Aspergillosis, Hospital-Acquired Infections, Pseudomonas Infections caused by a non--Leuconostoc spp. microorganism microorganism /mi·cro·or·gan·ism/ (-or´gah-nizm) a microscopic organism; those of medical interest include bacteria, fungi, and protozoa. isolated from a catheter, blood, or both, who were admitted to the same department and at the same time as the patients defined as case-patients. The variables analyzed are shown in Table 2. [FIGURE 1 OMITTED] Nosocomial infection criteria were those previously established by the Centers for Disease Control and Prevention Centers for Disease Control and Prevention (CDC), agency of the U.S. Public Health Service since 1973, with headquarters in Atlanta; it was established in 1946 as the Communicable Disease Center. (Atlanta, GA, USA) (12). A multiple logistic regression In statistics, logistic regression is a regression model for binomially distributed response/dependent variables. It is useful for modeling the probability of an event occurring as a function of other factors. model was developed to identify potential independent factors associated with acquisition of LM strains. Predictor variables with p<0.10 in univariate analysis were included in the multivariate model to enable adjustment. Statistical analyses were conducted with SPSS A statistical package from SPSS, Inc., Chicago (www.spss.com) that runs on PCs, most mainframes and minis and is used extensively in marketing research. It provides over 50 statistical processes, including regression analysis, correlation and analysis of variance. 14.0 software (SPSS Inc., Chicago, IL, USA). According to the multivariate analysis multivariate analysis, n a statistical approach used to evaluate multiple variables. multivariate analysis, n a set of techniques used when variation in several variables has to be studied simultaneously. , previous infections (38.2% were bacteremias) (odds ratio [OR] = 4.2) and parenteral nutrition (OR = 27.8) were associated with Leuconostoc spp. infection (Table 2). After the case-control study case-control study, n an investigation employing an epidemiologic approach in which previously existing incidents of a medical condition are used in lieu of gathering new information from a randomized population. , parenteral nutrition was suspected to be the source of the outbreak. [FIGURE 2 OMITTED] All case-patients received parenteral nutrition, with the exception of 2, although they received enteral nutrition Enteral nutrition Nourishment given through a tube or stoma directly into the small intestine, thus bypassing the upper digestive tract. Mentioned in: Electrolyte Supplements, Enterostomy, Necrotizing Enterocolitis . Parenteral nutrition is a putative source of the infection because all parenteral parenteral /pa·ren·ter·al/ (pah-ren´ter-al) not through the alimentary canal, but rather by injection through some other route, as subcutaneous, intramuscular, etc. par·en·ter·al adj. 1. and enteral nutrition bags are prepared in the central hospital pharmacy and then distributed to the different medical units in the hospital. This possibility was further supported by 1 finding: PFGE analysis of isolates obtained from a parenteral nutrition catheter connected to a patient during the second outbreak yielded the same genotype as the isolates obtained from blood from the same patient (Figure 2) and from another 3 physically separated, infected patients. The physical distance between these patients as well as the impossibility of retrograde displacement of the bacterial isolate from patient's blood makes it unlikely that the LM strain was acquired by contamination from the blood and indicates parenteral nutrition as the main source of LM transmission in the hospital outbreak. Microbiologic controls of parenteral nutrition were reinforced during the second outbreak, and as stated, only 6 cases were detected. Moreover, during the second outbreak, microbiologic analysis of environmental samples as well as samples from the digestive tract digestive tract n. See alimentary canal. Digestive tract The organs that perform digestion, or changing of food into a form that can be absorbed by the body. , skin, and throat of all patients involved did not yield any Leuconostoc strains. Parenteral nutrition controls performed in the hospital pharmacy department are now routinely assayed for LM isolation. Since the last LM outbreak in November 2006, no cases of Leuconostoc-associated bacteremia bacteremia: see septicemia. bacteremia Presence of bacteria in the blood. Short-term bacteremia follows dental or surgical procedures, especially if local infection or very high-risk surgery releases bacteria from isolated sites. have been reported in the hospital. Conclusions That 42 LM isolates from the first outbreak shared the same genotype and 4 of 6 isolates in the second outbreak also shared the same (another) genotype rules out the possibility of endogenous infections among patients and suggests a common source for each outbreak. The occurrence of cases in patients in areas that were physically separated rules out the possibility of indirect patient-to-patient spread through the hands of healthcare workers or contaminated contaminated, v 1. made radioactive by the addition of small quantities of radioactive material. 2. made contaminated by adding infective or radiographic materials. 3. an infective surface or object. hospital equipment (different departments do not share healthcare workers and equipment). Enteral enteral /en·ter·al/ (en´ter'l) enteric. en·ter·al adj. 1. Within or by way of the intestine, as distinguished from parenteral. 2. Enteric. and parenteral nutrition has previously been described (13,14) as a risk factor associated with Leuconostoc-infections, although no microbiologic evidence was provided in any of the studies. With regard to previous infections in the multiple logistic regression model, this may be related to the alteration of the immune system immune system Cells, cell products, organs, and structures of the body involved in the detection and destruction of foreign invaders, such as bacteria, viruses, and cancer cells. Immunity is based on the system's ability to launch a defense against such invaders. caused by the microorganism that caused the previous infections. This alteration may play a role facilitating the subsequent Leuconostoc spp. infection. Two previous reports have described hospital transmission of Leuconostoc spp (7,15); both outbreaks affected a small number of patients, and no epidemiologic studies were conducted to clarify the genetic relationship among the bacterial strains involved or the source of the nosocomial infection. Although up to 88 cases of Leuconostoc infection have been reported in the scientific literature in the past 25 years, these cases may not be comparable to those reported here, the largest nosocomial nosocomial /noso·co·mi·al/ (nos?o-ko´me-il) pertaining to or originating in a hospital. nos·o·co·mi·al adj. 1. Of or relating to a hospital. 2. outbreak caused by Leuconostoc spp. worldwide. This outbreak highlights the importance of LM as an emerging hospital pathogen in patients with underlying diseases and in whom parenteral nutrition may be the source of the initial infection and its spread. Every infection with LM could be a yet undetected outbreak and should result in an investigation that focuses on parenteral nutrition or products manufactured in a centralized hospital pharmacy. This study was partly funded by the Ministerio de Sanidad y Consumo, Instituto de Salud Carlos III, Spanish Network for Research in Infectious Diseases (REIPI RD06/0008), and FIS FIS n abbr (BRIT) (= Family Income Supplement) → ayuda estatal familiar P1061368. References (1.) Facklam R, Elliott JA. identification, classification, and clinical relevance of catalase-negative, gram-positive cocci cocci /coc·ci/ (kok´si) plural of coccus. cocci [L.] plural of coccus. , excluding streptococci Streptococcus (plural, streptococci) A genus of spherical-shaped anaerobic bacteria occurring in pairs or chains. Sydenham's chorea is considered a complication of a streptococcal throat infection. and enterococci enterococci bacteria in the genus Enterococcus. . Clin Microbiol Rev. 1995;8:479-95. (2.) Buu-Hoi. Branger CA, Acar FJ. Vancomycin-resistant streptococci or Leuconostoc spp. Antimicrob Agents Chemother. 1985;28:458-60. (3.) Fewer S, Miguel G, Domingo P, Pericas R, Prats G. Pulmonary infection due to Leuconostoc species in a patient with AIDS. Clin Infect Dis. 1995;21:225-6. (4.) Handwerger S, Horowitz H, Coburn K, Kolokathis A, Wormser GR Infection due to Leuconostoc species: six cases and review. Rev Infect Dis. 1990;12:602-10. (5.) Jimenez-Mejias ME, Becerril B, Gomez-Cia T, Del Nozal M, Palomino-Nicas J. Bacteriemia caused by Leuconostoc cremoris in a patient with severe burn injuries. Eur J Clin Microbiol Infect Dis. 1997;16:533-5. (6.) Albanese A, Spanu T, Sali M, Novezgno F, D'Inzeo T, Santagelo R, et al. Molecular identification of Leuconostoc mesenteroides as a cause of brain abscess Brain Abscess Definition Brain abscess is a bacterial infection within the brain. Description The brain is usually well insulated from infection by bacteria, protected by the skull, the meninges (tissue layers surrounding the brain), in an immunocompromised patient. J Clin Microbiol. 2006;44:3044-5. (7.) Cappelli EA, Barros RR, Camello TCF See Trenton Computer Festival. , Teixeira LM, Merquior VL. Leuconostoc pseudomesenteroides as a cause of nosocomial urinary tract infections urinary tract infection (UTI), n infection in one or more of the structures that make up the urinary system. Occurs more often in women and is most commonly caused by bacteria. . J Clin Microbiol. 1999;37:4124-6. (8.) Bernaldo de Quiros JC, Munoz P, Cercenado E, Hernandez Sampelayo T, Moreno S, Bouza E. Leuconostoc species as a cause of bacteremia: two case reports and a literature review. Eur J Clin Microbiol Infect Dis. 1991;10:505-9. (9.) Drancourt M, Bollet C, Carlioz A, Martelin R, Gayral JP, Raoult D. 16s ribosomal DNA sequence analysis of a large collection of environmental and clinical unidentifiable Adj. 1. unidentifiable - impossible to identify identifiable - capable of being identified bacterial isolates. J Clin Microbiol. 2000;38:3623-30. (10.) Clinical and Laboratory Standards Institute. Performance standards for antimicrobial susceptibility testing; fifteenth informational supplement. M100-S15. Wayne (PA): the Institute; 2005. (11.) Tenover FC, Arbeit RD, Goering RV, Mickelsen PA, Murray BE, Persing DH, et al. Interpreting chromosomal DNA restriction patterns produced by pulse-field gel electrophoresis: criteria for bacterial strain typing. J Clin Microbiol. 1995;33:2233-9. (12.) Garner JS, Jarvis WR, Emori TG, Horan TC, Hughes JM. CDC See Control Data, century date change and Back Orifice. CDC - Control Data Corporation definitions for nosocomial infections Nosocomial infections Infections that were not present before the patient came to a hospital, but were acquired by a patient while in the hospital. Mentioned in: Enterobacterial Infections, Staphylococcal Infections . Am J Infect Control. 1988;16: 128-40. (13.) Carapetis J, Bishop S, Davis J, Bell B, Hogg G. Leuconostoc sepsis in association with continuous enteral feeding: two case reports and a review. Pediatr Infect Dis J. 1994;13:816-23. (14.) Dhodapkar KM, Henry NK. Leuconostoc bacteremia in an infant with short-gut syndrome: case report and literature review. Mayo Clin Proc. 1996;71:1171-4. (15.) Scano F, Rossi L, Cattelan AM, Carretta G, Meneghetti F, Cadrobbi P, et al. Leuconostoc species: a case-cluster hospital infection. Scand J Infect Dis. 1999;31:371-3. Address for correspondence: German Bou, Servicio de Microbiologia. Complejo Hospitalario Universitario Juan Canalejo C/ Xubias de Arriba ar·ri·ba interj. Used as an exclamation of pleasure, approval, or elation. [Spanish, from Latin ad r s/n 15006 La Coruna, Spain; email: germanbou@canalejo.org German Bou, * Jesus Luis Saleta, * Juan Antonio Saez Nieto, ([dagger]) Mar Tomas, * Silvia Valdezate, ([dagger]) Dolores Dolores (or Delores) was a common given name (until the 1960s in the USA); it is cognate with the English word "dolorous" (meaning sorrowful) and equivalent in meaning. Sousa, * Francisco Lueiro, * Rosa Villanueva, * Maria Jose Pereira, * and Pedro Llinares * * Complejo Hospitalario Universitario Juan Canalejo, La Coruna, Spain; and ([dagger])Centro Nacional de Microbiologia, Majadahonda, Madrid, Spain M.T. is in receipt of a post-MIR research contract from the Instituto de Salud Carlos III. Dr Bou is senior researcher in the Research Unit for Clinical Microbiology at the Juan Canalejo Hospital, La Coruna, Spain. His main research interests are the molecular basis of antimicrobial resistance and the epidemiology of nosocomial infections.
Table 1. Clinical features of the case-control patients in the first
outbreak of Leuconostoc mesenteroides subsp. mesenteroides infection,
La Coruna, Spain, 2003-2004
Diagnosis * No. cases (%), No. controls (%),
n = 42 n = 61
Newborns 11 (26.2) 17 (27.9)
Adults (>1 y) 31 (73.8) 44 (72.1)
Tumors
Solid 9 (21.4) 13 (21.31)
Leukemia/lymphoma/
myeloma 1/5/0 (2.38/11.9/0) 3/4/3 (4.92/6.56/4.92)
Digestive tract disease
Pancreatitis 3 (7.14) 0
Necrotizing
enterocolitis 2 (4.76) 1 (1.64)
Ulcerous colitis/Crohn
disease 1/1 (2.38/2.38) 0/1 (0/1.64)
Cholecystitis 2 (4.76) 1 (1.64)
Bowel perforation 3 (7.14) 0
Bowel atresia 2 (4.76) 1 (1.64)
Bowel fistula 2 (4.76) 1 (1.64)
Prematurity 3 (7.14) 11 (18.03)
Infections 3 (7.14) 2 (3.28)
Cardiopathy 2 (4.76) 3 (4.92)
Chylothorax 4 (9.52) 0
Brain vascular disease 3 (7.14) 8 (13.11)
Immunosupression 18 (48.9) 36 (59.0)
Others 3 (7.14) 9 (14.75)
* Each patient may have >1 diagnosis.
([dagger]) Concomitant with Leuconostoc infection.
Table 2. Model for predicting infection by L. mesenteroides
subsp. mesenteroides (LM), La Coruna, Spain, 2003-2004 *
Cases, n = 42
Mean
Variable No. (%) (SD)
Age, y 34.3
(28.2)
Time between admission and 33.50
infection (38.4)
Charlson score 2.94
(2.13)
Previous surgery 29 (69)
Previous infections 31 (73.8)
Previous antimicrobial drug
therapy 37 (88.1)
Teicoplanin 12 (28.6)
Vancomycin 5 (11.9)
Central venous lines 39 (92.9)
Sex
Male 24 (57.1)
Urinary catheter 28 (66.7)
Enteral nutrition 18 (42.9)
Parenteral nutrition 40 (95.2)
Blood transfusion 24 (57.1)
Intubation 18 (42.9)
Tracheostomy 4 (9.5)
Treatment with steroids 8 (19)
Alteration of gastrointestinal
barrier ([double dagger]) 29 (69)
Controls, n = 61
Mean
Variable No. (%) (SD)
Age, y 44.4
(31.7)
Time between admission and 37.5
infection (100.9)
Charlson score 4.28
(2.38)
Previous surgery 23 (37.7)
Previous infections 15 (24.6)
Previous antimicrobial drug
therapy 42 (68.9)
Teicoplanin 4 (6.6)
Vancomycin 3 (4.9)
Central venous lines 41 (67.2)
Sex
Male 41 (67.2)
Urinary catheter 21 (34.4)
Enteral nutrition 23 (37.7)
Parenteral nutrition 26 (42.6)
Blood transfusion 31 (50.8)
Intubation 17 (27.9)
Tracheostomy 3 (4.9)
Treatment with steroids 12 (19.7)
Alteration of gastrointestinal
barrier ([double dagger]) 30 (49.2)
Crude OR
([dagger]) Adjusted OR
Variable (95% CI) (95% CI)
Age, y 0.99 (0.98-1.0)
Time between admission and 0.999 (0.994-1.0) NS
infection
Charlson score 0.76 (0.61-0.96) NS
Previous surgery 3.7 (1.6-8.5) NS
Previous infections 8.6 (3.5-21.3) 4.2 (1.2-14.7)
Previous antimicrobial drug
therapy 3.3 (1.1-9.9) NS
Teicoplanin 5.7 (1.7-19.2) NS
Vancomycin 2.6 (0.6-11.6)
Central venous lines 6.3 (1.7-23.0) NS
Sex
Male 0.7 (0.3-15)
Urinary catheter 3.7 (1.6-8.6) NS
Enteral nutrition 1.2 (0.6-2.8)
Parenteral nutrition 26.9 (6-121.6) 27.8 (5.5-141.1)
Blood transfusion 1.3 (0.6-2.8)
Intubation 1.9 (0.8-4.4)
Tracheostomy 2.0 (0.4-9.6)
Treatment with steroids 1 (0.4-2.6)
Alteration of gastrointestinal
barrier ([double dagger]) 2.3 (1.0-5.3) NS
Variable p value
Age, y
Time between admission and
infection
Charlson score
Previous surgery
Previous infections 0.023
Previous antimicrobial drug
therapy
Teicoplanin
Vancomycin
Central venous lines
Sex
Male
Urinary catheter
Enteral nutrition
Parenteral nutrition <0.000
Blood transfusion
Intubation
Tracheostomy
Treatment with steroids
Alteration of gastrointestinal
barrier ([double dagger])
* Values for 42 case patients and 61 control patients. SD, standard
deviation; OR, odds ratio; CI, confidence interval; NS, variable did
not meet criterion for remaining in the multivariate model. All
these variables were considered as potential risk factors for LM
infection. The LM infection was considered as an outcome variable.
([dagger]) (Predictor variables with p<0.10 in univariate analysis
were included in the multivariate model to enable simultaneous
adjustment.
([double dagger]) Any process that modifies the gastrointestinal
barrier (inflammation, atresia, resection, obstruction).
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