Skip to main content
Erschienen in: European Journal of Clinical Microbiology & Infectious Diseases 6/2010

01.06.2010 | Article

Correlation between Klebsiella pneumoniae carrying pLVPK-derived loci and abscess formation

verfasst von: H.-L. Tang, M.-K. Chiang, W.-J. Liou, Y.-T. Chen, H.-L. Peng, C.-S. Chiou, K.-S. Liu, M.-C. Lu, K.-C. Tung, Y.-C. Lai

Erschienen in: European Journal of Clinical Microbiology & Infectious Diseases | Ausgabe 6/2010

Einloggen, um Zugang zu erhalten

Abstract

Klebsiella pneumoniae-caused liver abscess (KLA) is an emerging infectious disease. However, factors other than K1-specific loci that contribute to the pathogenesis of this disease have not been identified. pLVPK is a 219,385-bp plasmid of K. pneumoniae CG43, an invasive K2 strain associated with KLA. We aimed in this study to evaluate the involvement of pLVPK in K. pneumoniae virulence and its clinical significance in abscess formation. A pLVPK-cured CG43 was isolated and its virulence was examined in a mouse model. The prevalence of pLVPK-derived loci terW, iutA, rmpA, silS, and repA was investigated in 207 clinical isolates by screening with specific primers. Loss of pLVPK abolished the ability of K. pneumoniae to disseminate into extraintestinal sites and, consequently, attenuated abscess formation in mice. Primary K. pneumoniae abscess isolates (n = 94) were more likely to be terW+-iutA+-rmpA+-silS+ than those related to non-abscess infections (n = 113) (62% vs. 27%; p < 0.0001). Logistic regression analysis indicated that the presence of the terW-rmpA-iutA-silS loci was a significant risk factor (odds ratio, 4.12; 95% confidence interval, 2.02–8.4; p < 0.0001) for abscess formation. pLVPK is a determinant for K. pneumoniae virulence and infection with strains carrying the pLVPK-derived terW-rmpA-iutA-silS loci may predispose patients to abscess formation.
Literatur
1.
Zurück zum Zitat Podschun R, Ullmann U (1998) Klebsiella spp. as nosocomial pathogens: epidemiology, taxonomy, typing methods, and pathogenicity factors. Clin Microbiol Rev 11(4):589–603PubMed Podschun R, Ullmann U (1998) Klebsiella spp. as nosocomial pathogens: epidemiology, taxonomy, typing methods, and pathogenicity factors. Clin Microbiol Rev 11(4):589–603PubMed
2.
Zurück zum Zitat McDonald MI (1984) Pyogenic liver abscess: diagnosis, bacteriology and treatment. Eur J Clin Microbiol 3(6):506–509CrossRefPubMed McDonald MI (1984) Pyogenic liver abscess: diagnosis, bacteriology and treatment. Eur J Clin Microbiol 3(6):506–509CrossRefPubMed
3.
Zurück zum Zitat Braiteh F, Golden MP (2007) Cryptogenic invasive Klebsiella pneumoniae liver abscess syndrome. Int J Infect Dis 11(1):16–22CrossRefPubMed Braiteh F, Golden MP (2007) Cryptogenic invasive Klebsiella pneumoniae liver abscess syndrome. Int J Infect Dis 11(1):16–22CrossRefPubMed
4.
Zurück zum Zitat Chan KS, Yu WL, Tsai CL, Cheng KC, Hou CC, Lee MC, Tan CK (2007) Pyogenic liver abscess caused by Klebsiella pneumoniae: analysis of the clinical characteristics and outcomes of 84 patients. Chin Med J (Engl) 120(2):136–139 Chan KS, Yu WL, Tsai CL, Cheng KC, Hou CC, Lee MC, Tan CK (2007) Pyogenic liver abscess caused by Klebsiella pneumoniae: analysis of the clinical characteristics and outcomes of 84 patients. Chin Med J (Engl) 120(2):136–139
5.
Zurück zum Zitat Chung DR, Lee SS, Lee HR, Kim HB, Choi HJ, Eom JS, Kim JS, Choi YH, Lee JS, Chung MH, Kim YS, Lee H, Lee MS, Park CK (2007) Emerging invasive liver abscess caused by K1 serotype Klebsiella pneumoniae in Korea. J Infect 54(6):578–583CrossRefPubMed Chung DR, Lee SS, Lee HR, Kim HB, Choi HJ, Eom JS, Kim JS, Choi YH, Lee JS, Chung MH, Kim YS, Lee H, Lee MS, Park CK (2007) Emerging invasive liver abscess caused by K1 serotype Klebsiella pneumoniae in Korea. J Infect 54(6):578–583CrossRefPubMed
6.
Zurück zum Zitat Fang FC, Sandler N, Libby SJ (2005) Liver abscess caused by magA + Klebsiella pneumoniae in North America. J Clin Microbiol 43(2):991–992CrossRefPubMed Fang FC, Sandler N, Libby SJ (2005) Liver abscess caused by magA + Klebsiella pneumoniae in North America. J Clin Microbiol 43(2):991–992CrossRefPubMed
7.
Zurück zum Zitat Ko WC, Paterson DL, Sagnimeni AJ, Hansen DS, Von Gottberg A, Mohapatra S, Casellas JM, Goossens H, Mulazimoglu L, Trenholme G, Klugman KP, McCormack JG, Yu VL (2002) Community-acquired Klebsiella pneumoniae bacteremia: global differences in clinical patterns. Emerg Infect Dis 8(2):160–166CrossRefPubMed Ko WC, Paterson DL, Sagnimeni AJ, Hansen DS, Von Gottberg A, Mohapatra S, Casellas JM, Goossens H, Mulazimoglu L, Trenholme G, Klugman KP, McCormack JG, Yu VL (2002) Community-acquired Klebsiella pneumoniae bacteremia: global differences in clinical patterns. Emerg Infect Dis 8(2):160–166CrossRefPubMed
8.
Zurück zum Zitat Mine T (2005) Virulent Klebsiella pneumoniae strains and liver abscess with metastatic lesions. Hepatol Res 31(1):5–6CrossRefPubMed Mine T (2005) Virulent Klebsiella pneumoniae strains and liver abscess with metastatic lesions. Hepatol Res 31(1):5–6CrossRefPubMed
9.
Zurück zum Zitat Nadasy KA, Domiati-Saad R, Tribble MA (2007) Invasive Klebsiella pneumoniae syndrome in North America. Clin Infect Dis 45(3):e25–e28CrossRefPubMed Nadasy KA, Domiati-Saad R, Tribble MA (2007) Invasive Klebsiella pneumoniae syndrome in North America. Clin Infect Dis 45(3):e25–e28CrossRefPubMed
10.
Zurück zum Zitat Pastagia M, Arumugam V (2008) Klebsiella pneumoniae liver abscesses in a public hospital in Queens, New York. Travel Med Infect Dis 6(4):228–233CrossRefPubMed Pastagia M, Arumugam V (2008) Klebsiella pneumoniae liver abscesses in a public hospital in Queens, New York. Travel Med Infect Dis 6(4):228–233CrossRefPubMed
11.
Zurück zum Zitat Wang JH, Liu YC, Lee SS, Yen MY, Chen YS, Wang JH, Wann SR, Lin HH (1998) Primary liver abscess due to Klebsiella pneumoniae in Taiwan. Clin Infect Dis 26(6):1434–1438CrossRefPubMed Wang JH, Liu YC, Lee SS, Yen MY, Chen YS, Wang JH, Wann SR, Lin HH (1998) Primary liver abscess due to Klebsiella pneumoniae in Taiwan. Clin Infect Dis 26(6):1434–1438CrossRefPubMed
12.
Zurück zum Zitat Yang CC, Yen CH, Ho MW, Wang JH (2004) Comparison of pyogenic liver abscess caused by non-Klebsiella pneumoniae and Klebsiella pneumoniae. J Microbiol Immunol Infect 37(3):176–184PubMed Yang CC, Yen CH, Ho MW, Wang JH (2004) Comparison of pyogenic liver abscess caused by non-Klebsiella pneumoniae and Klebsiella pneumoniae. J Microbiol Immunol Infect 37(3):176–184PubMed
13.
Zurück zum Zitat Yeh KM, Kurup A, Siu LK, Koh YL, Fung CP, Lin JC, Chen TL, Chang FY, Koh TH (2007) Capsular serotype K1 or K2, rather than magA and rmpA, is a major virulence determinant for Klebsiella pneumoniae liver abscess in Singapore and Taiwan. J Clin Microbiol 45(2):466–471CrossRefPubMed Yeh KM, Kurup A, Siu LK, Koh YL, Fung CP, Lin JC, Chen TL, Chang FY, Koh TH (2007) Capsular serotype K1 or K2, rather than magA and rmpA, is a major virulence determinant for Klebsiella pneumoniae liver abscess in Singapore and Taiwan. J Clin Microbiol 45(2):466–471CrossRefPubMed
14.
Zurück zum Zitat Ohmori S, Shiraki K, Ito K, Inoue H, Ito T, Sakai T, Takase K, Nakano T (2002) Septic endophthalmitis and meningitis associated with Klebsiella pneumoniae liver abscess. Hepatol Res 22(4):307–312CrossRefPubMed Ohmori S, Shiraki K, Ito K, Inoue H, Ito T, Sakai T, Takase K, Nakano T (2002) Septic endophthalmitis and meningitis associated with Klebsiella pneumoniae liver abscess. Hepatol Res 22(4):307–312CrossRefPubMed
15.
Zurück zum Zitat Hu BS, Lau YJ, Shi ZY, Lin YH (1999) Necrotizing fasciitis associated with Klebsiella pneumoniae liver abscess. Clin Infect Dis 29(5):1360–1361CrossRefPubMed Hu BS, Lau YJ, Shi ZY, Lin YH (1999) Necrotizing fasciitis associated with Klebsiella pneumoniae liver abscess. Clin Infect Dis 29(5):1360–1361CrossRefPubMed
16.
Zurück zum Zitat Lindstrom ST, Healey PR, Chen SC (1997) Metastatic septic endophthalmitis complicating pyogenic liver abscess caused by Klebsiella pneumoniae. Aust NZ J Med 27(1):77–78 Lindstrom ST, Healey PR, Chen SC (1997) Metastatic septic endophthalmitis complicating pyogenic liver abscess caused by Klebsiella pneumoniae. Aust NZ J Med 27(1):77–78
17.
Zurück zum Zitat Lee CH, Leu HS, Wu TS, Su LH, Liu JW (2005) Risk factors for spontaneous rupture of liver abscess caused by Klebsiella pneumoniae. Diagn Microbiol Infect Dis 52(2):79–84CrossRefPubMed Lee CH, Leu HS, Wu TS, Su LH, Liu JW (2005) Risk factors for spontaneous rupture of liver abscess caused by Klebsiella pneumoniae. Diagn Microbiol Infect Dis 52(2):79–84CrossRefPubMed
18.
Zurück zum Zitat Yu WL, Ko WC, Cheng KC, Lee HC, Ke DS, Lee CC, Fung CP, Chuang YC (2006) Association between rmpA and magA genes and clinical syndromes caused by Klebsiella pneumoniae in Taiwan. Clin Infect Dis 42(10):1351–1358CrossRefPubMed Yu WL, Ko WC, Cheng KC, Lee HC, Ke DS, Lee CC, Fung CP, Chuang YC (2006) Association between rmpA and magA genes and clinical syndromes caused by Klebsiella pneumoniae in Taiwan. Clin Infect Dis 42(10):1351–1358CrossRefPubMed
19.
Zurück zum Zitat Yu WL, Ko WC, Cheng KC, Lee CC, Lai CC, Chuang YC (2008) Comparison of prevalence of virulence factors for Klebsiella pneumoniae liver abscesses between isolates with capsular K1/K2 and non-K1/K2 serotypes. Diagn Microbiol Infect Dis 62(1):1–6CrossRefPubMed Yu WL, Ko WC, Cheng KC, Lee CC, Lai CC, Chuang YC (2008) Comparison of prevalence of virulence factors for Klebsiella pneumoniae liver abscesses between isolates with capsular K1/K2 and non-K1/K2 serotypes. Diagn Microbiol Infect Dis 62(1):1–6CrossRefPubMed
20.
Zurück zum Zitat Lin TL, Lee CZ, Hsieh PF, Tsai SF, Wang JT (2008) Characterization of integrative and conjugative element ICEKp1-associated genomic heterogeneity in a Klebsiella pneumoniae strain isolated from a primary liver abscess. J Bacteriol 190(2):515–526CrossRefPubMed Lin TL, Lee CZ, Hsieh PF, Tsai SF, Wang JT (2008) Characterization of integrative and conjugative element ICEKp1-associated genomic heterogeneity in a Klebsiella pneumoniae strain isolated from a primary liver abscess. J Bacteriol 190(2):515–526CrossRefPubMed
21.
Zurück zum Zitat Fung CP, Siu LK (2007) Virulence of Klebsiella pneumoniae serotype K2 should not be underestimated in K. pneumoniae liver abscess. Clin Infect Dis 45(11):1530–1531, author reply 1532–1533CrossRefPubMed Fung CP, Siu LK (2007) Virulence of Klebsiella pneumoniae serotype K2 should not be underestimated in K. pneumoniae liver abscess. Clin Infect Dis 45(11):1530–1531, author reply 1532–1533CrossRefPubMed
22.
Zurück zum Zitat Lee HC, Chuang YC, Yu WL, Lee NY, Chang CM, Ko NY, Wang LR, Ko WC (2006) Clinical implications of hypermucoviscosity phenotype in Klebsiella pneumoniae isolates: association with invasive syndrome in patients with community-acquired bacteraemia. J Intern Med 259(6):606–614CrossRefPubMed Lee HC, Chuang YC, Yu WL, Lee NY, Chang CM, Ko NY, Wang LR, Ko WC (2006) Clinical implications of hypermucoviscosity phenotype in Klebsiella pneumoniae isolates: association with invasive syndrome in patients with community-acquired bacteraemia. J Intern Med 259(6):606–614CrossRefPubMed
23.
Zurück zum Zitat Ma LC, Fang CT, Lee CZ, Shun CT, Wang JT (2005) Genomic heterogeneity in Klebsiella pneumoniae strains is associated with primary pyogenic liver abscess and metastatic infection. J Infect Dis 192(1):117–128CrossRefPubMed Ma LC, Fang CT, Lee CZ, Shun CT, Wang JT (2005) Genomic heterogeneity in Klebsiella pneumoniae strains is associated with primary pyogenic liver abscess and metastatic infection. J Infect Dis 192(1):117–128CrossRefPubMed
24.
Zurück zum Zitat Fung CP, Chang FY, Lee SC, Hu BS, Kuo BI, Liu CY, Ho M, Siu LK (2002) A global emerging disease of Klebsiella pneumoniae liver abscess: is serotype K1 an important factor for complicated endophthalmitis? Gut 50(3):420–424CrossRefPubMed Fung CP, Chang FY, Lee SC, Hu BS, Kuo BI, Liu CY, Ho M, Siu LK (2002) A global emerging disease of Klebsiella pneumoniae liver abscess: is serotype K1 an important factor for complicated endophthalmitis? Gut 50(3):420–424CrossRefPubMed
25.
Zurück zum Zitat Chen YT, Chang HY, Lai YC, Pan CC, Tsai SF, Peng HL (2004) Sequencing and analysis of the large virulence plasmid pLVPK of Klebsiella pneumoniae CG43. Gene 337:189–198CrossRefPubMed Chen YT, Chang HY, Lai YC, Pan CC, Tsai SF, Peng HL (2004) Sequencing and analysis of the large virulence plasmid pLVPK of Klebsiella pneumoniae CG43. Gene 337:189–198CrossRefPubMed
26.
Zurück zum Zitat Tu YC, Lu MC, Chiang MK, Huang SP, Peng HL, Chang HY, Jan MS, Lai YC (2009) Genetic requirements for Klebsiella pneumoniae-induced liver abscess in an oral infection model. Infect Immun 77(7):2657–2671CrossRefPubMed Tu YC, Lu MC, Chiang MK, Huang SP, Peng HL, Chang HY, Jan MS, Lai YC (2009) Genetic requirements for Klebsiella pneumoniae-induced liver abscess in an oral infection model. Infect Immun 77(7):2657–2671CrossRefPubMed
27.
Zurück zum Zitat Tsay RW, Siu LK, Fung CP, Chang FY (2002) Characteristics of bacteremia between community-acquired and nosocomial Klebsiella pneumoniae infection: risk factor for mortality and the impact of capsular serotypes as a herald for community-acquired infection. Arch Intern Med 162(9):1021–1027CrossRefPubMed Tsay RW, Siu LK, Fung CP, Chang FY (2002) Characteristics of bacteremia between community-acquired and nosocomial Klebsiella pneumoniae infection: risk factor for mortality and the impact of capsular serotypes as a herald for community-acquired infection. Arch Intern Med 162(9):1021–1027CrossRefPubMed
28.
Zurück zum Zitat El-Mansi M, Anderson KJ, Inche CA, Knowles LK, Platt DJ (2000) Isolation and curing of the Klebsiella pneumoniae large indigenous plasmid using sodium dodecyl sulphate. Res Microbiol 151(3):201–208CrossRefPubMed El-Mansi M, Anderson KJ, Inche CA, Knowles LK, Platt DJ (2000) Isolation and curing of the Klebsiella pneumoniae large indigenous plasmid using sodium dodecyl sulphate. Res Microbiol 151(3):201–208CrossRefPubMed
29.
Zurück zum Zitat Fang CT, Lai SY, Yi WC, Hsueh PR, Liu KL, Chang SC (2007) Klebsiella pneumoniae genotype K1: an emerging pathogen that causes septic ocular or central nervous system complications from pyogenic liver abscess. Clin Infect Dis 45(3):284–293CrossRefPubMed Fang CT, Lai SY, Yi WC, Hsueh PR, Liu KL, Chang SC (2007) Klebsiella pneumoniae genotype K1: an emerging pathogen that causes septic ocular or central nervous system complications from pyogenic liver abscess. Clin Infect Dis 45(3):284–293CrossRefPubMed
30.
Zurück zum Zitat Tsai FC, Huang YT, Chang LY, Wang JT (2008) Pyogenic liver abscess as endemic disease, Taiwan. Emerg Infect Dis 14(10):1592–1600CrossRefPubMed Tsai FC, Huang YT, Chang LY, Wang JT (2008) Pyogenic liver abscess as endemic disease, Taiwan. Emerg Infect Dis 14(10):1592–1600CrossRefPubMed
31.
Zurück zum Zitat Chuang YP, Fang CT, Lai SY, Chang SC, Wang JT (2006) Genetic determinants of capsular serotype K1 of Klebsiella pneumoniae causing primary pyogenic liver abscess. J Infect Dis 193(5):645–654CrossRefPubMed Chuang YP, Fang CT, Lai SY, Chang SC, Wang JT (2006) Genetic determinants of capsular serotype K1 of Klebsiella pneumoniae causing primary pyogenic liver abscess. J Infect Dis 193(5):645–654CrossRefPubMed
32.
Zurück zum Zitat Fang CT, Chuang YP, Shun CT, Chang SC, Wang JT (2004) A novel virulence gene in Klebsiella pneumoniae strains causing primary liver abscess and septic metastatic complications. J Exp Med 199(5):697–705CrossRefPubMed Fang CT, Chuang YP, Shun CT, Chang SC, Wang JT (2004) A novel virulence gene in Klebsiella pneumoniae strains causing primary liver abscess and septic metastatic complications. J Exp Med 199(5):697–705CrossRefPubMed
33.
Zurück zum Zitat Nassif X, Fournier JM, Arondel J, Sansonetti PJ (1989) Mucoid phenotype of Klebsiella pneumoniae is a plasmid-encoded virulence factor. Infect Immun 57(2):546–552PubMed Nassif X, Fournier JM, Arondel J, Sansonetti PJ (1989) Mucoid phenotype of Klebsiella pneumoniae is a plasmid-encoded virulence factor. Infect Immun 57(2):546–552PubMed
34.
Zurück zum Zitat Nassif X, Sansonetti PJ (1986) Correlation of the virulence of Klebsiella pneumoniae K1 and K2 with the presence of a plasmid encoding aerobactin. Infect Immun 54(3):603–608PubMed Nassif X, Sansonetti PJ (1986) Correlation of the virulence of Klebsiella pneumoniae K1 and K2 with the presence of a plasmid encoding aerobactin. Infect Immun 54(3):603–608PubMed
35.
Zurück zum Zitat Wu KM, Li LH, Yan JJ, Tsao N, Liao TL, Tsai HC, Fung CP, Chen HJ, Liu YM, Wang JT, Fang CT, Chang SC, Shu HY, Liu TT, Chen YT, Shiau YR, Lauderdale TL, Su IJ, Kirby R, Tsai SF (2009) Genome sequencing and comparative analysis of Klebsiella pneumoniae NTUH-K2044, a strain causing liver abscess and meningitis. J Bacteriol 191(14):4492–4501CrossRefPubMed Wu KM, Li LH, Yan JJ, Tsao N, Liao TL, Tsai HC, Fung CP, Chen HJ, Liu YM, Wang JT, Fang CT, Chang SC, Shu HY, Liu TT, Chen YT, Shiau YR, Lauderdale TL, Su IJ, Kirby R, Tsai SF (2009) Genome sequencing and comparative analysis of Klebsiella pneumoniae NTUH-K2044, a strain causing liver abscess and meningitis. J Bacteriol 191(14):4492–4501CrossRefPubMed
36.
Zurück zum Zitat Ku YH, Chuang YC, Yu WL (2008) Clinical spectrum and molecular characteristics of Klebsiella pneumoniae causing community-acquired extrahepatic abscess. J Microbiol Immunol Infect 41(4):311–317PubMed Ku YH, Chuang YC, Yu WL (2008) Clinical spectrum and molecular characteristics of Klebsiella pneumoniae causing community-acquired extrahepatic abscess. J Microbiol Immunol Infect 41(4):311–317PubMed
37.
Zurück zum Zitat Jacoby GA, Sutton L, Knobel L, Mammen P (1983) Properties of IncP-2 plasmids of Pseudomonas spp. Antimicrob Agents Chemother 24(2):168–175PubMed Jacoby GA, Sutton L, Knobel L, Mammen P (1983) Properties of IncP-2 plasmids of Pseudomonas spp. Antimicrob Agents Chemother 24(2):168–175PubMed
38.
Zurück zum Zitat Lai YC, Peng HL, Chang HY (2003) RmpA2, an activator of capsule biosynthesis in Klebsiella pneumoniae CG43, regulates K2 cps gene expression at the transcriptional level. J Bacteriol 185(3):788–800CrossRefPubMed Lai YC, Peng HL, Chang HY (2003) RmpA2, an activator of capsule biosynthesis in Klebsiella pneumoniae CG43, regulates K2 cps gene expression at the transcriptional level. J Bacteriol 185(3):788–800CrossRefPubMed
39.
Zurück zum Zitat West SE, Sparling PF (1987) Aerobactin utilization by Neisseria gonorrhoeae and cloning of a genomic DNA fragment that complements Escherichia coli fhuB mutations. J Bacteriol 169(8):3414–3421PubMed West SE, Sparling PF (1987) Aerobactin utilization by Neisseria gonorrhoeae and cloning of a genomic DNA fragment that complements Escherichia coli fhuB mutations. J Bacteriol 169(8):3414–3421PubMed
40.
Zurück zum Zitat Hill VT, Townsend SM, Arias RS, Jenabi JM, Gomez-Gonzalez I, Shimada H, Badger JL (2004) TraJ-dependent Escherichia coli K1 interactions with professional phagocytes are important for early systemic dissemination of infection in the neonatal rat. Infect Immun 72(1):478–488CrossRefPubMed Hill VT, Townsend SM, Arias RS, Jenabi JM, Gomez-Gonzalez I, Shimada H, Badger JL (2004) TraJ-dependent Escherichia coli K1 interactions with professional phagocytes are important for early systemic dissemination of infection in the neonatal rat. Infect Immun 72(1):478–488CrossRefPubMed
Metadaten
Titel
Correlation between Klebsiella pneumoniae carrying pLVPK-derived loci and abscess formation
verfasst von
H.-L. Tang
M.-K. Chiang
W.-J. Liou
Y.-T. Chen
H.-L. Peng
C.-S. Chiou
K.-S. Liu
M.-C. Lu
K.-C. Tung
Y.-C. Lai
Publikationsdatum
01.06.2010
Verlag
Springer-Verlag
Erschienen in
European Journal of Clinical Microbiology & Infectious Diseases / Ausgabe 6/2010
Print ISSN: 0934-9723
Elektronische ISSN: 1435-4373
DOI
https://doi.org/10.1007/s10096-010-0915-1

Weitere Artikel der Ausgabe 6/2010

European Journal of Clinical Microbiology & Infectious Diseases 6/2010 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.