Multilocus sequence typing and ftsI sequencing: a powerful tool for surveillance of penicillin-binding protein 3-mediated beta-lactam resistance in nontypeable Haemophilus influenzae

Table 6 Beta-lactam susceptibility according to PBP3 resistance genotypes

Study groups^a	Resistance genotypes^b		n	MIC₅₀/MIC₉₀(mg/L) and susceptibility categorization (%)^c
Study groups^a	Resistance genotypes^b		n	AMP^c	AMC^c	PIP^c	CXM	CTX	MEM
Resistant group	High-rPBP3	Group III	1	8/-	16/-	0.06/-	>16/-	0.25/-	1/-
Resistant group	High-rPBP3	Group III	1	(0/100)	(0/100)		(0/0/100)	(0/100)	(0/100/0)
		Group III-like	2	2/4	8/16	0.06/0.12	>16/>16	0.06/0.12	0.03/0.03
		Group III-like	2	(0/100)	(0/100)		(0/0/100)	(100/0)	(100/0/0)
	Low-rPBP3	Group II	111	2/4	4/8	0.03/0.06	8/8	0.03/0.12	0.12/0.5
	Low-rPBP3	Group II	111	(40/60)	(45/55)		(33/11/56)	(94/6)	(80/20/0)
		Group I	2	0.5/1	0.25/1	0.03/0.06	0.5/16	0.06/0.25	0.016/0.06
		Group I	2	(100/0)	(100/0)		(50/0/50)	(50/50)	(100/0/0)
	sPBP3		60	0.25/0.5	0.5/2	0.004/0.03	1/8	0.008/0.06	0.03/0.12
	sPBP3		60	(98/2)	(98/2)		(74/13/13)	(98/2)	(100/0/0)
Susceptible group	sPBP3		19	0.12/0.5	0.5/2	0.004/0.06	0.5/8	0.004/0.03	0.03/0.12
Susceptible group	sPBP3		19	(100/0)	(95/5)		(79/11/11)	(100/0)	(100/0/0)

^aSee Figure 1.
^bSee Table 1.
^cMICs (microbroth dilution) and susceptibility categorization (S/R or S/I/R) according to EUCAST clinical breakpoints [37]. The following breakpoints were used (S≤/R>): Ampicillin (AMP), 1/1; amoxicillin (AMC), 2/2; cefuroxime (CXM), 1/2; cefotaxime (CTX), 0.12/0.12; meropenem (MEM), 0.25/1. Clinical breakpoints for piperacillin and piperacillin-tazobactam are not set by EUCAST. Meningitis breakpoints were used for categorization of meropenem.
^dFor beta-lactamase positive isolates, ampicillin, amoxicillin and piperacillin MICs were determined in combination with sulbactam (4 mg/L), clavulanate (2 mg/L) and tazobactam (4 mg/L), respectively.