Rapid Increase of Genetically Diverse Methicillin-resistant Staphylococcus Aureus, Copenhagen, Denmark

Mette Damkjær Bartels; Kit Boye; Anders Rhod Larsen; Robert Skov; Henrik Westh

Emerging Infectious Diseases. 2007;13(10):1533-1540.

Abstract and Introduction

Abstract

In Copenhagen, methicillin-resistant Staphylococcus aureus (MRSA) accounted for <15 isolates per year during 1980-2002. However, since 2003 an epidemic increase has been observed, with 33 MRSA cases in 2003 and 110 in 2004. We analyzed these 143 cases epidemiologically and characterized isolates by pulsed-field gel electrophoresis, Staphylococcus protein A (spa) typing, multilocus sequence typing, staphylococcal chromosome cassette (SCC) mec typing, and detection of Panton-Valentine leukocidin (PVL) genes. Seventy-one percent of cases were community-onset MRSA (CO-MRSA); of these, 36% had no identified risk factors. We identified 29 spa types (t) and 16 sequence types (STs) belonging to 8 clonal complexes and 3 ST singletons. The most common clonal types were t024/ST8-IV, t019/ST30-IV, t044/ST80-IV, and t008/ST8-IV (USA300). A total of 86% of isolates harbored SCCmec IV, and 44% had PVL. Skin and soft tissue infections dominated. CO-MRSA with diverse genetic backgrounds is rapidly emerging in a low MRSA prevalence area.

Introduction

For many years, methicillin-resistant Staphylococcus aureus (MRSA) has been a serious and common nosocomial pathogen in hospitals outside the Nordic countries and the Netherlands.^[1] Community-onset MRSA (CO-MRSA) was first reported in Western Australia in the early 1990s^[2] and has, especially during the past 5 years, emerged as a global problem.^[1,3] CO-MRSA in the United States has mostly been caused by the Panton-Valentine leukocidin (PVL)-positive clones USA400 (sequence type [ST]1) and more recently by USA300 (ST8).^[1,4,5,6,7] In Europe the increase in CO-MRSA has mostly been attributed to the PVL-positive ST80 clone.^[3,8] In Denmark, since 1980, MRSA has accounted for <100 MRSA isolates per year nationwide (www.danmap.org/pdffiles/danmap_2005.pdf). At our laboratory, MRSA has been isolated from <15 patients per year until 2002. Approximately half of the MRSA cases found in Denmark during these years were imported, i.e., through patients transferred from foreign hospitals.^[9]

Since 2003 the number of MRSA-positive persons increased both nationally and in Copenhagen. Nationally, the number increased from 50-105 new cases per year to 243 in 2003, 549 in 2004, and 864 in 2005. At Hvidovre Hospital, we found MRSA in 5 persons in 2001, 14 in 2002, 33 in 2003, 110 in 2004, and 170 in 2005. We describe the epidemiology of the emergence of MRSA in Copenhagen in 2003 and 2004 and characterize the genetic background of the isolates.

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Cite this: Rapid Increase of Genetically Diverse Methicillin-resistant Staphylococcus Aureus, Copenhagen, Denmark - Medscape - Oct 01, 2007.

Abstract and Introduction
Materials and Methods
Results
Discussion
References

Table 1. Demographics, Infection Types, and Distribution of MRSA Types in 143 Cases of MRSA*
	Community onset, community risk	Community onset, no risk	Hospital acquired in Denmark	Community onset, healthcare associated	Imported
No. cases	30	35	37	36
Male, %	67	46	57	42
Median age, y (range)	27 (1-74)	32 (0-90)	80 (28-94)	82 (6-95)
Carrier, no.	8	1	2	2	4 ^†
Type of infection, no.
SSTI	22	29	17	23
Blood	0	0	2	2
Deep-seated abscess, no.	0	1	5	3
UTI	0	4	8	5
LRTI	0	0	3	1	1 ^†
Four most common CCs (87% of all isolates)
CC 8, %	23	34	81	69
t008, no.	3	7	0	2
t024, no.	3	5	28	20
CC 80, %	20	34	3	0
CC 30, %	50	6	0	0
CC 5, %	3	11	5	8
Other MLST types,%	4	15	11	23
PVL positive, %	83	80	8	17
SCCmec IV, %	93	89	89	81

^*MRSA, methicillin-resistant Staphylococcus aureus; SSTI, skin and soft tissue infection; UTI, urinary tract infection; LRTI, lower respiratory tract infection; CC, clonal complex; MLST, multilocus sequence typing; PVL, Panton-Valentine leukocidin; SCC, staphylococcal chromosome cassette.

^†A t037/ST239-III was imported from Greece, where this MRSA is common;^[20] ST239 is closely related to ST8 and is the well-known pandemic Brazilian/Hungarian clone;^[21] t041/ST111 was imported from an Italian hospital; t003/ST225-II (New York clone) was imported from Germany; t354/ST22-IV, a variant of EMRSA15, was imported from Lanzarote (Spain); and t067/ST125-I was imported from Spain.

Table 1. Demographics, Infection Types, and Distribution of MRSA Types in 143 Cases of MRSA*
	Community onset, community risk	Community onset, no risk	Hospital acquired in Denmark	Community onset, healthcare associated	Imported
No. cases	30	35	37	36
Male, %	67	46	57	42
Median age, y (range)	27 (1-74)	32 (0-90)	80 (28-94)	82 (6-95)
Carrier, no.	8	1	2	2	4 ^†
Type of infection, no.
SSTI	22	29	17	23
Blood	0	0	2	2
Deep-seated abscess, no.	0	1	5	3
UTI	0	4	8	5
LRTI	0	0	3	1	1 ^†
Four most common CCs (87% of all isolates)
CC 8, %	23	34	81	69
t008, no.	3	7	0	2
t024, no.	3	5	28	20
CC 80, %	20	34	3	0
CC 30, %	50	6	0	0
CC 5, %	3	11	5	8
Other MLST types,%	4	15	11	23
PVL positive, %	83	80	8	17
SCCmec IV, %	93	89	89	81

Appendix Table. Resistance Patterns of 143 Multiresistant Isolates of Staphylococcus Aureus
CC/singleton	Beta	E,C	E,C,F	E,C,G	E,C,M	E,C,T	F	G	M	M,T	T	F,T	E,C,F,M,T	E,C,F,T	E,C,G,M,T	E,C,M,T	E,C,G,M	Total
CC1	3																	3
CC5		1	3		4		1			1						2		12
CC8	4	36	3	2	19	4	1				1		1		1	2	1	74
CC15	1																	1
CC22	4				1				1									6
CC30	16											1						17
CC45			1					2			2					1		6
CC97	1																	1
ST80							1					16		2				19
ST111																	1	1
ST152								1										1
NT											1							1
Total	29	37	7	2	24	4	3	3	1	1	4	17	1	2	1	5	2	143
HA and CO-HCA	6	28	3	2	20	3	1	2	0	1	4	0	1	1	0	4	2	78
CO-NR and CO-CR	23	9	4	0	4	1	2	1	1	0	0	17	0	1	1	1	0	65

^*Numbers in each column are the number of isolates with the specific resistance profile. In the rows the resistance pattern in the clonal complex (CC)/sequence type (ST) singletons and in hospital-acquired/healthcare-associated/community risk/no risk (HA/CO-HCA) MRSA and community onset-no health care association-community risk (CO-NR/CO-CR) MRSA are presented. Beta = resistant only to beta-lactams; E = erythromycin; C = clindamycin; F = fucidic acid; G = gentamicin; M = moxifloxacin; T = tetracycline; NT = nontypeable.

Appendix Table. Resistance Patterns of 143 Multiresistant Isolates of Staphylococcus Aureus
CC/singleton	Beta	E,C	E,C,F	E,C,G	E,C,M	E,C,T	F	G	M	M,T	T	F,T	E,C,F,M,T	E,C,F,T	E,C,G,M,T	E,C,M,T	E,C,G,M	Total
CC1	3																	3
CC5		1	3		4		1			1						2		12
CC8	4	36	3	2	19	4	1				1		1		1	2	1	74
CC15	1																	1
CC22	4				1				1									6
CC30	16											1						17
CC45			1					2			2					1		6
CC97	1																	1
ST80							1					16		2				19
ST111																	1	1
ST152								1										1
NT											1							1
Total	29	37	7	2	24	4	3	3	1	1	4	17	1	2	1	5	2	143
HA and CO-HCA	6	28	3	2	20	3	1	2	0	1	4	0	1	1	0	4	2	78
CO-NR and CO-CR	23	9	4	0	4	1	2	1	1	0	0	17	0	1	1	1	0	65

Table 2. Genetic Backgrounds and Epidemiologic Information on MRSA Isolates*
CC	Multilocus ST	Spa types	Isolates, no. (total in CC)	No. PVL-positive isolates	SCCmec types (no. isolates)	HA/HCA MRSA or CR/NR MRSA % in the CC
CC1	ST1 ST748 ^†	t175 t127	2 1 (3)	2 0	IV V	33/67
CC5	ST5 ST125 ST225	t002 t067 t003	7 1 4 (12)	7 0 4	I (3), II (1), IV(3) I II	58/42
CC8	ST8 ST239	t024, t008, t430, t064, t351 t037	56/12/2 1/1 3 (75)	12 (t008) 0 0	IV IV III (2), NT (1)	74/26
CC15	ST15	t084	1	0	V	100/0
CC22	ST22 ST737*	t005,t022,t354 t541 t542	2/1/1 1 1 (6)	0 0 0	IV, NT (t022) IV IV	50/50
CC30	ST30	t019	17	17	IV	0/100
CC45	ST45	t015, t026, t065 t116, t350	2/1/1 1/1 (6)	0 0	IV, V (t026 and t116)	100/0
CC97	ST97	t359	1	1	V	100/0
Singleton	ST80	t044, t376, t455	16/2/1 (19)	19	IV	5/95
Singleton	ST111	t041	1	0	I	100/0
Singleton	ST152	t355	1	1	V	0/100
Total			142	63

^*MRSA, methicillin-resistant Staphylococcus aureus; CC, clonal complex; ST, sequence type; PVL, Panton-Valentine leukocidin; SCC, staphylococcal chromosome cassette; HA/HCA/CR/NR, hospital acquired/healthcare associated/community risk/no risk. One isolate could only be typed by spa and multilocus sequence typing and is not included in the table.
^†New ST.

Table 2. Genetic Backgrounds and Epidemiologic Information on MRSA Isolates*
CC	Multilocus ST	Spa types	Isolates, no. (total in CC)	No. PVL-positive isolates	SCCmec types (no. isolates)	HA/HCA MRSA or CR/NR MRSA % in the CC
CC1	ST1 ST748 ^†	t175 t127	2 1 (3)	2 0	IV V	33/67
CC5	ST5 ST125 ST225	t002 t067 t003	7 1 4 (12)	7 0 4	I (3), II (1), IV(3) I II	58/42
CC8	ST8 ST239	t024, t008, t430, t064, t351 t037	56/12/2 1/1 3 (75)	12 (t008) 0 0	IV IV III (2), NT (1)	74/26
CC15	ST15	t084	1	0	V	100/0
CC22	ST22 ST737*	t005,t022,t354 t541 t542	2/1/1 1 1 (6)	0 0 0	IV, NT (t022) IV IV	50/50
CC30	ST30	t019	17	17	IV	0/100
CC45	ST45	t015, t026, t065 t116, t350	2/1/1 1/1 (6)	0 0	IV, V (t026 and t116)	100/0
CC97	ST97	t359	1	1	V	100/0
Singleton	ST80	t044, t376, t455	16/2/1 (19)	19	IV	5/95
Singleton	ST111	t041	1	0	I	100/0
Singleton	ST152	t355	1	1	V	0/100
Total			142	63

Table 2. Genetic Backgrounds and Epidemiologic Information on MRSA Isolates*
CC	Multilocus ST	Spa types	Isolates, no. (total in CC)	No. PVL-positive isolates	SCCmec types (no. isolates)	HA/HCA MRSA or CR/NR MRSA % in the CC
CC1	ST1 ST748 ^†	t175 t127	2 1 (3)	2 0	IV V	33/67
CC5	ST5 ST125 ST225	t002 t067 t003	7 1 4 (12)	7 0 4	I (3), II (1), IV(3) I II	58/42
CC8	ST8 ST239	t024, t008, t430, t064, t351 t037	56/12/2 1/1 3 (75)	12 (t008) 0 0	IV IV III (2), NT (1)	74/26
CC15	ST15	t084	1	0	V	100/0
CC22	ST22 ST737*	t005,t022,t354 t541 t542	2/1/1 1 1 (6)	0 0 0	IV, NT (t022) IV IV	50/50
CC30	ST30	t019	17	17	IV	0/100
CC45	ST45	t015, t026, t065 t116, t350	2/1/1 1/1 (6)	0 0	IV, V (t026 and t116)	100/0
CC97	ST97	t359	1	1	V	100/0
Singleton	ST80	t044, t376, t455	16/2/1 (19)	19	IV	5/95
Singleton	ST111	t041	1	0	I	100/0
Singleton	ST152	t355	1	1	V	0/100
Total			142	63

Table 2. Genetic Backgrounds and Epidemiologic Information on MRSA Isolates*
CC	Multilocus ST	Spa types	Isolates, no. (total in CC)	No. PVL-positive isolates	SCCmec types (no. isolates)	HA/HCA MRSA or CR/NR MRSA % in the CC
CC1	ST1 ST748 ^†	t175 t127	2 1 (3)	2 0	IV V	33/67
CC5	ST5 ST125 ST225	t002 t067 t003	7 1 4 (12)	7 0 4	I (3), II (1), IV(3) I II	58/42
CC8	ST8 ST239	t024, t008, t430, t064, t351 t037	56/12/2 1/1 3 (75)	12 (t008) 0 0	IV IV III (2), NT (1)	74/26
CC15	ST15	t084	1	0	V	100/0
CC22	ST22 ST737*	t005,t022,t354 t541 t542	2/1/1 1 1 (6)	0 0 0	IV, NT (t022) IV IV	50/50
CC30	ST30	t019	17	17	IV	0/100
CC45	ST45	t015, t026, t065 t116, t350	2/1/1 1/1 (6)	0 0	IV, V (t026 and t116)	100/0
CC97	ST97	t359	1	1	V	100/0
Singleton	ST80	t044, t376, t455	16/2/1 (19)	19	IV	5/95
Singleton	ST111	t041	1	0	I	100/0
Singleton	ST152	t355	1	1	V	0/100
Total			142	63

Table 2. Genetic Backgrounds and Epidemiologic Information on MRSA Isolates*
CC	Multilocus ST	Spa types	Isolates, no. (total in CC)	No. PVL-positive isolates	SCCmec types (no. isolates)	HA/HCA MRSA or CR/NR MRSA % in the CC
CC1	ST1 ST748 ^†	t175 t127	2 1 (3)	2 0	IV V	33/67
CC5	ST5 ST125 ST225	t002 t067 t003	7 1 4 (12)	7 0 4	I (3), II (1), IV(3) I II	58/42
CC8	ST8 ST239	t024, t008, t430, t064, t351 t037	56/12/2 1/1 3 (75)	12 (t008) 0 0	IV IV III (2), NT (1)	74/26
CC15	ST15	t084	1	0	V	100/0
CC22	ST22 ST737*	t005,t022,t354 t541 t542	2/1/1 1 1 (6)	0 0 0	IV, NT (t022) IV IV	50/50
CC30	ST30	t019	17	17	IV	0/100
CC45	ST45	t015, t026, t065 t116, t350	2/1/1 1/1 (6)	0 0	IV, V (t026 and t116)	100/0
CC97	ST97	t359	1	1	V	100/0
Singleton	ST80	t044, t376, t455	16/2/1 (19)	19	IV	5/95
Singleton	ST111	t041	1	0	I	100/0
Singleton	ST152	t355	1	1	V	0/100
Total			142	63

Table 2. Genetic Backgrounds and Epidemiologic Information on MRSA Isolates*
CC	Multilocus ST	Spa types	Isolates, no. (total in CC)	No. PVL-positive isolates	SCCmec types (no. isolates)	HA/HCA MRSA or CR/NR MRSA % in the CC
CC1	ST1 ST748 ^†	t175 t127	2 1 (3)	2 0	IV V	33/67
CC5	ST5 ST125 ST225	t002 t067 t003	7 1 4 (12)	7 0 4	I (3), II (1), IV(3) I II	58/42
CC8	ST8 ST239	t024, t008, t430, t064, t351 t037	56/12/2 1/1 3 (75)	12 (t008) 0 0	IV IV III (2), NT (1)	74/26
CC15	ST15	t084	1	0	V	100/0
CC22	ST22 ST737*	t005,t022,t354 t541 t542	2/1/1 1 1 (6)	0 0 0	IV, NT (t022) IV IV	50/50
CC30	ST30	t019	17	17	IV	0/100
CC45	ST45	t015, t026, t065 t116, t350	2/1/1 1/1 (6)	0 0	IV, V (t026 and t116)	100/0
CC97	ST97	t359	1	1	V	100/0
Singleton	ST80	t044, t376, t455	16/2/1 (19)	19	IV	5/95
Singleton	ST111	t041	1	0	I	100/0
Singleton	ST152	t355	1	1	V	0/100
Total			142	63

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Rapid Increase of Genetically Diverse Methicillin-resistant Staphylococcus Aureus, Copenhagen, Denmark

Abstract and Introduction

Abstract

Introduction

Tables

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Tables

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References

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