Table 4.

Summary of In Vitro Susceptibility Studies for Staphylococcus Species and β-Lactams

Study	Isolates (No.)	Conclusions	Comments	Source
S. aureus
1	MRSA (70)	MSSA strains were highly susceptible (all MIC ≤4 µg/mL) to cephalothin, cefoperazone, and cefotaxime compared to MRSA strains. MIC50 and MIC90 of MSSA strains were 8- to-128-fold lower than MRSA isolates (MIC90 >32 for MRSA).	Data support the deduction of cephalothin, cefoperazone, and cefotaxime results based on oxacillin or cefoxitin results.	[53]
	MSSA (24)
		MRSA stains had MIC range of 0.25–256 µg/mL. Strains with high MICs to methicillin (MIC ≥64 µg/mL) also had high MICs to cephalothin (MIC ≥32 µg/mL), cefoperazone (MIC ≥64 µg/mL), and cefotaxime (MIC ≥128 µg/mL).
2	MRSA (98)	MRSA isolates had high MIC50 and MIC90 values: cefuroxime (MIC50 >256, MIC90 >256) cefotaxime (MIC50 = 32, MIC90 >256), and cefepime (MIC50 = 48, MIC90 >256).	Majority of MRSA isolates have MICs >8 µg/mL to cefuroxime, cefotaxime, and cefepime, supporting the deduction of results for these agents based on oxacillin or cefoxitin results.	[49]
		Sixteen isolates exhibited MIC <2 µg/mL to cephalothin; 10 isolates were susceptible to cefuroxime, cefotaxime, or cefepime (MIC ≤8 µg/mL).	Inclusion of breakpoints for β-lactams other than penicillin, oxacillin, and cefoxitin can lead to falsely susceptible results in MRS.
3	MSSA (1313)	MSSA isolates were 100% susceptible to cefepime (MIC ≤8 µg/mL), 99.8% susceptible to ceftriaxone (MIC ≤8 µg/mL), and 0% resistant to ceftriaxone (MIC ≥64 µg/mL) and cefepime (MIC ≥32 µg/mL).	Susceptibility of staphylococci to cefepime and ceftriaxone can be inferred from oxacillin or cefoxitin results.	[48]
4	MRSA (4453)	MSSA isolates had ceftriaxone MIC90 of 4 µg/mL, 96% of isolates had MICs to ceftriaxone <4 µg/mL, and 0.3% were considered resistant; 3.7% were not categorized as susceptible or resistant.	It is critical to know breakpoint criteria and methods used when evaluating reports in the literature. Authors specified that FDA breakpoints were applied when available but did not provide actual MIC values on those isolates categorized as resistant with MICs >4 µg/mL.	[47]
	MSSA (4016)
		4% of MSSA isolates had ceftriaxone MICs >4 µg/mL and were considered ceftriaxone nonsusceptible using FDA breakpoints (MIC ≤4 µg/mL, susceptible). The actual MIC for these isolates was not reported.
			This emphasizes that the inclusion of breakpoints for these ceftriaxone and meropenem can lead to falsely resistant results in MSSA.
		MSSA isolates demonstrated MIC90 of ≤0.12 µg/mL to meropenem.
		MRSA isolates were all (100%) resistant to ceftriaxone (MIC >64 µg/mL).	Results for ceftriaxone and meropenem can be inferred from oxacillin or cefoxitin results.
Coagulase-negative staphylococci
5	MRCNS (26)	100% of MSCNS isolates were susceptible to cefradine, ceftriaxone, cephalothin, and cefamandole (MIC ≤8 µg/mL).	MSCNS can be considered susceptible to cefradine, ceftriaxone, cephalothin, and cefamandole.	[50]
	MSCNS (36)
		Susceptible results for MRCNS isolates: 7.7% for ceftriaxone (MIC ≤8 µg/mL), 84.6% for cephalothin (MIC ≤8 µg/mL), 96.2% for cefamandole (MIC ≤8 µg/mL), and 0% for cefradine (MIC ≤8 µg/mL)	Presence of heteroresistant populations of MRS can lead to falsely susceptible results for cephalosporins.
			Inclusion of breakpoints for β-lactams other than the penicillin, oxacillin, and cefoxitin can lead to falsely susceptible results in MRCNS.
		Susceptible results for highly methicillin-resistant (MIC >128 µg/mL) subpopulation of CNS: 0% for ceftriaxone, 3.8% for cephalothin, 46% for cefamandole, and 0% for cefradine.
6	MSCNS (182)	100% of MSCNS isolates were susceptible to cefepime (MIC ≤8 µg/mL) and 98.3% were susceptible to ceftriaxone (MIC ≤8 µg/mL). The MIC90 for ceftriaxone was 4 µg/mL, and 0.6% (1 isolate) was considered resistant; 1.1% of isolates were not categorized as susceptible or resistant.	Susceptibility of staphylococci to cefepime and ceftriaxone can be inferred from oxacillin or cefoxitin results.	[48]
			This emphasizes that the inclusion of breakpoints for these cefepime and ceftriaxone can lead to falsely resistant results in MSCNS.
		1.7% of MSCNS had ceftriaxone MICs >8 µg/mL and were considered ceftriaxone nonsusceptible using CLSI breakpoints (MIC ≤8 µg/mL, susceptible).

Abbreviations: CLSI, Clinical and Laboratory Standards Institute; CNS, coagulase negative staphylococci; FDA, US Food and Drug Administration; MIC, minimum inhibitory concentration; MRS, methicillin-resistant staphylococci; MRSA, methicillin-resistant Staphylococcus aureus; MRCNS, methicillin-resistant coagulase negative staphylococci; MSCNS, methicillin-susceptible coagulase negative staphylococci; MSSA, methicillinsusceptible Staphylococcus aureus.