Antimicrobial Resistance in Haemophilus influenzae Respiratory Tract Isolates in Korea: Results of a Nationwide Acute Respiratory Infections Surveillance

DOI: 10.1128/AAC.00966-09

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FIG. 1.
Dendrogram and PFGE patterns of 33 BLNAR strains and 28 BLPACR strains of H. influenzae. The dendrogram was constructed by the unweighted-pair group method of average linkage (UPGMA). The scale measures similarity values. Strains and their subtypes are shown on the right column.

TABLE 1.

Clinical characteristics of the patients

↵ a RTI, respiratory tract infection. Preliminary diagnosis was made on the basis of the history and physical examinations and included 41 patients with more than one RTI.

TABLE 2.

In vitro susceptibilities of the 540 H. influenzae isolates to eight antimicrobial agents^a

Antimicrobial agent	All isolates (n = 540)				BLNAS (n = 224)				BLPAR (n = 255)				BLNAR (n = 33)				BLPACR (n = 28)
Antimicrobial agent	MIC₅₀ (μg/ml)	MIC₉₀ (μg/ml)	MIC range (μg/ml)	% S	MIC₅₀ (μg/ml)	MIC₉₀ (μg/ml)	MIC range (μg/ml)	% S	MIC₅₀ (μg/ml)	MIC₉₀ (μg/ml)	MIC range (μg/ml)	% S	MIC₅₀ (μg/ml)	MIC₉₀ (μg/ml)	MIC range (μg/ml)	% S	MIC₅₀ (μg/ml)	MIC₉₀ (μg/ml)	MIC range (μg/ml)	% S
Ampicillin	16	256	≤0.5->512	41.5	1	1	≤0.5-1	100.0	128	256	2->512	0.0	2	8	2-8	0.0	256	>512	4->512	0.0
Amoxicillin- clavulanate	2	8	≤0.25-32	89.6	2	8	≤0.25-16	96.4	2	4	0.25-4	100.0	8	8	1-16	39.4	8	16	8-32	0.0
Clarithromycin	8	16	≤1-64	81.3	8	16	≤2-64	84.4	8	16	2-32	83.5	8	32	4-64	51.5	8	16	1-32	71.4
Chloramphenicol	0.5	1	0.25-16	91.9	0.5	0.5	0.25-4	100.0	0.5	8	0.25-16	85.1	0.5	1	0.5-4	93.9	0.5	8	0.25-8	85.7
Cefaclor	8	32	1-128	83.0	8	16	1-128	85.3	8	32	4-128	82.0	8	32	8-64	84.8	8	64	4-128	71.4
Cefuroxime	2	8	0.25-32	76.7	2	8	0.25-32	82.1	2	8	0.5-16	82.0	8	16	1-32	33.3	8	32	1-32	35.7
Cefotaxime	0.063	0.125	≤0.031-2	100.0	0.063	0.25	≤0.031-2	100.0	0.063	0.125	≤0.031-0.25	100.0	0.063	1	0.031-2	100.0	0.063	1	0.063-1	100.0
Levofloxacin	0.016	0.031	≤0.008-0.5	100.0	0.016	0.031	≤0.008-0.031	100.0	0.016	0.031	≤0.008-0.5	100.0	0.016	0.016	0.008-0.031	100.0	0.016	0.031	0.016-0.063	100.0

↵ a BLNAS, β-lactamase-negative, ampicillin-susceptible H. influenzae; BLPAR, β-lactamase-positive, ampicillin-resistant H. influenzae; BLNAR, β-lactamase-negative, ampicillin-resistant H. influenzae; BLPACR, β-lactamase-positive, amoxicillin-clavulanate-resistant H. influenzae; % S, percentage with susceptiblity.

TABLE 3.

MIC range of ampicillin and resistance mechanisms in 540 H. influenzae isolates

Characteristic	Ampicillin MIC (μg/ml)
Characteristic	<0.5	1	2	4	8	16	32	64	128	256	512	>512
Total no. of strains (n = 540)	106	118	28	9	6	15	24	68	86	48	21	11
No. of β-lactamase-positive strains (n = 283)	0	0	3	4	3	15	24	68	86	48	21	11
TEM-1 gene only (n = 268)	0	0	3	4	3	14	21	61	84	46	21	11
ROB-1 gene only (n = 9)	0	0	0	0	0	1	2	5	0	1	0	0
Both TEM-1 and ROB-1 genes (n = 4)	0	0	0	0	0	0	1	1	1	1	0	0
No TEM-1 or ROB-1 gene (n = 2)	0	0	0	0	0	0	0	1	1	0	0	0
No. of BLNAR strains (n = 33)	0	0	25	5	3	0	0	0	0	0	0	0

TABLE 4.

Deduced amino acid substitutions in PBP 3 of 33 BLNAR strains compared with the Rd strain in this study

Group^a	No. of strains	Amino acid substitution
		Amino acid substitution														Ampicillin			Cefuroxime		Cefotaxime
				Ser311	Asp350	Ser357	Met377	Ser385	Leu389	Ile449	Gly490	Ala502	Arg517	Asn526	MIC	Range	MIC	Range	MIC	Range
I	3		Asn	Asp	Ile	Thr					His		2	2	13.3	8-16	0.25	0.25
IIa	1								Glu			Lys	4	2-8	9.3	4-16	0.063	0.063
	1		Asn		Ile							Lys
	1		Asn		Ile				Glu			Lys
IIb	2									Val		Lys	2.2	2-8	6	2-8	0.069	0.063-0.125
	3		Asn		Ile					Val		Lys
	5		Asn		Ile				Glu	Val		Lys
IIc	7	Pro								Thr		Lys	2.8	2-8	11.4	2-16	0.194	0.063-1
	1							Val		Thr		Lys
	1		Asn	Asp	Ile	Thr				Thr		Lys
	1		Asn	Asp		Thr	Phe			Thr		Lys
IId	3							Val				Lys	2.7	2-4	8	4-16	0.708	0.063-2
III	3		Asn	Asp	Ile	Thr	Phe					Lys	5.3	4-8	13.3	4-32	1.7	1-2
Other^b	1												2		2		0.063

↵ a A total of 33 BLNAR strains were classified into six groups (I, IIa, IIb, IIc, IId, and III) based on previously proposed criteria (4, 19).
↵ b One isolate had no ftsI gene mutation.

TABLE 5.

Deduced amino acid substitutions in PBP 3 of 28 BLPACR strains compared with the Rd strain in this study

Group^a	No. of strains	Amino acid substitution
		Amino acid substitution														Ampicillin			Cefuroxime		Cefotaxime
				Asp350	Ser357	Ala368	Met377	Ser385	Ala437	Ile449	Gly490	Ala502	Arg517	Asn526	MIC	Range	MIC	Range	MIC	Range
I	2	Asn	Asp		Ile	Thr					His		192	128-256	32	32	0.188	0.125-0.25
IIa	1	Asn			Ile							Lys	288	64-512	2	2	0.532	0.063-1
	1	Asn			Ile	Thr						Lys
IIb	14	Asn			Ile					Val		Lys	230	4-512	11.4	1-32	0.188	0.063-1
	2									Val		Lys
	1	Asn			Ile				Glu	Val		Lys
IIc	2			Thr						Thr		Lys	208	64-512	6.5	2-16	0.079	0.063-0.125
	1	Asn	Asp				Ser			Thr		Lys
	1	Asn								Thr		Lys
IId	2							Val				Lys	512	512	4	4	0.094	0.063-0.125
Other^b	1	Asn					Ser						512		8		0.125

↵ a A total of 28 BLPACR strains were classified into the six groups based on the previously proposed criteria (4, 19).
↵ b One isolate hasn't been included in the subgroups mentioned above in this study.