. 2022 Dec 22;4(6):dlac125. doi: 10.1093/jacamr/dlac125

Table 2.

Details for the in vitro studies and in vitro surveillance studies

Author, year, country	Sample source and size^a	Indication	Penems and carbapenems	Enterobacterales species evaluated and results
In vitro studies
Dawoud et al.,⁶³ 2020, India	Clinical isolates N = 210	NR	Faropenem Imipenem	Resistance to faropenem and imipenem, respectively E. coli (n = 44): 2.3% and 4.5% K. pneumoniae (n = 34): 0% and 9.6%
Gandra et al.,⁶⁶ 2020, USA	US CDC isolate bank N = 4	NR	Faropenem Imipenem Meropenem Doripenem Ertapenem	In vitro development of resistance to faropenem, change in MIC (mg/L) 1 to 64 within 10 days for two isolates, and 2 to 64 within 7 days for two isolates MIC range (mg/L) for imipenem; meropenem; doripenem; ertapenem ESBL-producing E. coli: 1–4; 2 to >8; 2 to >4; 8 to >8 Non-ESBL-producing E. coli: 1; ≤0.5; ≤0.5; ≤0.25
Karlowsky et al.,⁶⁰ 2019, Canada	Clinical isolates N = 539	NR	Sulopenem	MIC range (mg/L) E. coli: 0.015–0.12 MIC₅₀ (mg/L) E. coli: 0.03 MIC₉₀ (mg/L) E. coli: 0.03
Nakamura et al.,⁶⁴ 2014, Japan	Clinical isolates N = 210	NR	Faropenem	Rate of resistance (%) to faropenem^b E. coli: 0.6% (CLSI and EUCAST); 4.6% (JSC cystitis); 31.6% (JSC pyelonephritis) K. pneumoniae: 2.7% (CLSI and EUCAST); 5.4% (JSC cystitis); 37.8% (JSC pyelonephritis) MIC₅₀ (mg/L) EBSL-producing E. coli: 1 EBSL-producing K. pneumoniae: 1 MIC₉₀ (mg/L) EBSL-producing E. coli: 2 EBSL-producing K. pneumoniae: 2
Hu et al.,⁶⁸ 2014, USA	Clinical isolates N = 135	NR	Faropenem Imipenem Meropenem Ertapenem Tebipenem	Mean (range) inhibition zone diameter (mm) for faropenem; imipenem; meropenem; ertapenem; tebipenem K. pneumoniae carbapenemase positive: E. coli: 6 (6); 16 (12–20); 15 (10–21); 13 (6–20); 16 (8–22) K. pneumoniae: 6 (6); 11 (6–22); 9 (6–20); 8 (6–16); 10 (6–21) Enterobacter spp.: 6 (6); 15 (7–23); 14 (7–20); 12 (6–17); 16 (7–22) K. pneumoniae carbapenemase negative: E. coli: 19 (10–24); 26 (22–30); 26 (25–30); 26 (22–30); 28 (26–32) K. pneumoniae: 19 (12–23); 26 (23–30); 26 (19–30); 26 (13–28); 28 (20–30) Enterobacter spp.: 16.5 (10–22); 23 (19–25); 25.5 (16–28); 24.5 (14–28); 27 (19–29) Zone diameter of 6 mm, for faropenem as a predictor of carbapenemase activity: 100% sensitivity and 100% specificity
Day et al.,⁶⁷ 2013, International	Clinical isolates N = 453 (N = 248 part 1, N = 205 part 2)	NR	Faropenem Imipenem Meropenem Doripenem Ertapenem	Enterobacterales included in disc susceptibility testing: E. coli, Klebsiella spp., Enterobacter spp., Citrobacter spp., P. mirabilis, Providencia rettgeri and Salmonella spp. (all β-lactamase-producing) Mean (range) inhibition zone diameter (mm) for faropenem; imipenem; meropenem; doripenem; ertapenem CPE: 6 (6–12); 17 (6–24); 14 (6–28); 15 (6–26); 10 (6–28) Non-CPE: 19 (6–30); 27 (16–36); 28 (12–36); 28 (13–35); 25 (6–36) Zone diameter of 6 mm for faropenem as a predictor of carbapenemase activity Part 1: 99% sensitivity and 94% specificity Part 2: 98% sensitivity and 87% specificity
Mushtaq et al.,⁵⁶ 2007, UK	Clinical isolates N = 847	NR	Faropenem Imipenem	MIC range (mg/L) for faropenem and imipenem, respectively E. coli CTX-M ESBL: 0.5–8 and 0.06–1 E. coli non-CTX-M ESBL: 0.25–8 and 0.06–0.5 E. coli AmpC: 0.5–16 and 0.06–0.5 Klebsiella spp. CTX-M ESBL: 0.12–16 and 0.12–2 Klebsiella spp. non-CTX-M ESBL: 0.12–16 and 0.12–2 Klebsiella oxytoca hyperproducing K1 enzyme: 0.25–1 and 0.12–0.5 Enterobacter spp. CTX-M ESBL: 1–8 and 0.12–1 Enterobacter spp. non-CTX-M ESBL: 1–16 and 0.06–1 Enterobacter spp. AmpC-derepressed: 0.5–16 and 0.12–2 Citrobacter spp. CTX-M ESBL: 2 and 0.25–0.5 Citrobacter spp. non-CTX-M ESBL: 0.5–1 and 0.12–1 Citrobacter spp. AmpC-derepressed: 0.5–8 and 0.25–1 Serratia spp. non-CTX-M ESBL: 1–2 and 0.25–0.5 Serratia spp. AmpC-derepressed: 4–16 and 0.12–2 M. morganii. AmpC-derepressed: 0.5–16 and 1–4 (All cephalosporin resistant)
Piddock et al.,⁵⁷ 2003, UK	Clinical isolates N = 170	NR	Faropenem Imipenem	MIC range (mg/L) for faropenem and imipenem, respectively Ciprofloxacin-resistant E. coli: <0.06–0.5 and 0.125–0.125 MIC₅₀ (mg/L) for faropenem and imipenem, respectively S. pneumoniae: <0.06 and <0.008 S. aureus: <0.006 and 1 Enterococcus spp.^b: 16 and 64 E. coli: 0.125 and 0.125 S. typhimurium: 0.125 and 0.25 P. aeruginosa: 64 and 1 Bacteroides fragilis: 0.5 and <0.125 C. jejuni: 0.25 and 0.12 MIC₉₀ (mg/L) for faropenem and imipenem, respectively S. pneumoniae: 0.5 and 0.25 S. aureus: 16 and 4 Enterococcus spp.^c: >32 and 128 E. coli: 0.25 and 0.125 S. typhimurium: 0.25 and 0.5 P. aeruginosa: 128 and 8 B. fragilis: 8 and 4 C. jejuni: 0.25 and 0.25
Miyazaki et al.,⁵⁸ 2001, Japan	Clinical isolates N = 483	NR	L-036 Faropenem Imipenem	MIC range (mg/L) for L-036; faropenem; imipenem E. coli: ≤0.063; 0.125–2; ≤0.063–0.25 K. pneumoniae: ≤0.063–0.5; 0.25–4; 0.125–0.5 MIC₅₀ (mg/L) for L-036; faropenem; imipenem E. coli: ≤0.063; 0.5; 0.125 K. pneumoniae: ≤0.063; 0.5; 0.25 MIC₉₀ (mg/L), for L-036, faropenem, imipenem E. coli: ≤0.063; 0.5; 0.125 K. pneumoniae: ≤0.063; 0.5; 0.25 MIC (mg/mL) in vivo in mice, for L-084 (prodrug) and faropenem, respectively Penicillin-susceptible S. pneumoniae TUH39: 0.0005 and 0.001
Okuda et al.,⁵⁹ 2000, Japan	Standard strains and clinical isolates N = 758	NR	Faropenem DU-6681a R-95867	MIC range (mg/L) for faropenem; DU-6681a; R-95856 E. coli: 0.12–2; ≤0.008–0.03; ≤0.008–0.06 K. pneumoniae: 0.25 to >128; ≤0.008–2; 0.015–4 S. marcescens: 2–128; 0.03–32; 0.06–32 Enterobacter spp.: 0.25–8; 0.015–0.25; 0.03–2 C. freundii: 1–4; 0.015–0.06; 0.03–0.5 Proteus spp.: 0.5–8; 0.03–0.5; 0.03–0.5 M. morganii: 1–8; 0.06–0.5; 0.06–1 Shigella spp.: 0.25–1; ≤0.008–0.03; 0.015–0.06 MIC₅₀ (mg/L) for faropenem; DU-6881a;R-95856 E. coli: 1; ≤0.008; 0.015 K. pneumoniae: 0.5; 0.015; 0.015 S. marcescens: 8; 0.12; 0.5 Enterobacter spp.: 2–4; 0.03; 0.25 C. freundii: 2; 0.03; 0.12 Proteus spp.: 2; 0.06–0.12; 0.12 M. morganii: 2; 0.25; 0.5 MIC₉₀ (mg/L) for faropenem; DU-6881a; R-95856 E. coli: 1; 0.015; 0.03 K. pneumoniae: 1; 0.06; 0.06 S. marcescens: 32; 0.25; 2 Enterobacter spp.: 4–8; 0.12; 0.5–2 C. freundii: 4; 0.06, 0.5 Proteus spp.: 4–8; 0.25–0.5; 0.25–0.5 M. morganii: 8, 0.25, 1
Arcamone et al.,⁶⁵ 2000, Italy	NR	NR	MEN 10700 Ritipenem	General findings Citing other sources, MEN 10700 showed good to excellent activity against most Enterobacterales, and had a spectrum of activity similar to ritipenem and faropenem, but with higher activity on Enterobacter and Citrobacter species Stability (after 190 min incubation at 37°C), MEN 10700 and ritipenem, respectively 68% unchanged and 35% unchanged AUC (mg/L × min) in vivo in rats, for MEN 11505 (prodrug) and ritipenem acoxil (prodrug), respectively 283.2 and 229.0 Relative bioavailability in vivo in rats, for MEN 11505 (prodrug) and ritipenem acoxil (prodrug), respectively 43% and 23%
Woodcock et al.,⁵⁵ 1997, UK	Standard strains and clinical isolates N = 726	NR	Faropenem	MIC range (mg/L) E. coli: 0.06–8 Klebsiella spp.: 0.06–8 Proteus spp.: 0.25–4 M. morganii: 0.06–4 Serratia spp.: 1–128 Enterobacter spp.: 0.5–16 Citrobacter spp.: 0.25–4 Salmonella spp.: 0.5 Shigella spp.: 0.25–0.5 Providencia stuartii: 0.06–4 MIC₅₀ (mg/L) E. coli: 0.5 Klebsiella spp.: 0.5 Proteus spp.: 1 M. morganii: 1 Serratia spp.: 2 Enterobacter spp.: 2 Citrobacter spp.: 0.5 Salmonella spp.: 0.5 Shigella spp.: 0.5 P. stuartii: 1 MIC₉₀ (mg/L) E. coli: 1 Klebsiella spp.: 2 Proteus spp.: 2–4 M. morganii: 2 Serratia spp.: 32 Enterobacter spp.: 4 Citrobacter spp.: 4 Salmonella spp.: 0.5 Shigella spp.: 0.5 P. stuartii: 2
Hamilton-Miller et al.,⁶¹ 1997, UK	Clinical isolates N = 539	NR	MEN 10700 Ritipenem	MIC range (mg/L) for MEN 10 700 and ritipenem, respectively E. coli: 0.25–1 and 1 K. pneumoniae: 0.5–1 and 1–2 Enterobacter spp.: 0.5–4 and 1–32 C. freundii: 0.5–4 and 4–32 P. mirabilis: 4–8 and 4–32 M. morganii: 1–16 and 4–16 S. marcescens: 0.5–8 and 4–16 Providencia spp.: 1–16 and 1–32 MIC₅₀ (mg/L) for MEN 10 700 and ritipenem, respectively E. coli: 0.5 and 1 K. pneumoniae: 1 and 1 Enterobacter spp.: 2 and 16 C. freundii: 1 and 8 P. mirabilis: 8 and 4 M. morganii: 2 and 8 S. marcescens: 2 and 8 Providencia spp.: 2–8 and 4–16 MIC₉₀ (mg/L) for MEN 10 700 and ritipenem, respectively E. coli: 0.5 and 1 K. pneumoniae: 1 and 1 Enterobacter spp.: 2 and 32 C. freundii: 2 and 16 P. mirabilis: 8 and 4 M. morganii: 16 and 16 S. marcescens: 4 and 8 Providencia spp.: 8–16 and 16–32
Frean et al.,⁶² 1996, Namibia	Clinical isolates N = 100	Plague	Faropenem	MIC range (mg/L) Y. pestis: <0.03–0.5 MIC₅₀ (mg/L) Y. pestis: 0.25 MIC₉₀ (mg/L) Y. pestis: 0.5
In vitro surveillance studies
Yanagihara et al.,⁷² 2020, Japan	Clinical isolates N = 1062	Respiratory infections	Faropenem Imipenem Meropenem Doripenem Biapenem Panipenem	MIC range (mg/L) for faropenem; imipenem; meropenem; doripenem; biapenem; panipenem K. pneumoniae: 0.25–8; 0.125–2; ≤0.06–0.25; ≤0.06–0.5; ≤0.06–4; 0.125–1 MIC₅₀ (mg/L) K. pneumoniae: 0.5; 0.25; ≤0.06; ≤0.06; 0.25; 0.25 MIC₉₀ (mg/L) K. pneumoniae: 1; 1; ≤0.06; 0.125; 1; 0.5
Watanabe et al.,⁷¹ 2012, Japan	Clinical isolates N = 684	Respiratory infections	Faropenem Imipenem Meropenem Doripenem Biapenem Panipenem	MIC range (mg/L) for faropenem; imipenem; meropenem; doripenem; biapenem; panipenem K. pneumoniae: 0.125–32; ≤0.06–1; ≤0.06–0.125; ≤0.06–0.125; ≤0.06–1; ≤0.06–0.5 MIC₅₀ (mg/L) K. pneumoniae: 0.5; 0.125; ≤0.06; ≤0.06; 0.125; 0.125 MIC₉₀ (mg/L) K. pneumoniae: 0.5; 0.5; ≤0.06; ≤0.06; 0.5; 0.5
Niki et al.,⁶⁹ 2011, Japan	Clinical isolates N = 1097	Respiratory infections	Faropenem Imipenem Meropenem Doripenem Biapenem Panipenem	MIC range (mg/L) for faropenem; imipenem; meropenem; doripenem; biapenem; panipenem K. pneumoniae: 0.125–8; ≤0.06–2; ≤0.06–0.25; ≤0.06–0.25; ≤0.06–1; ≤0.06–2 MIC₅₀ (mg/L) K. pneumoniae: 0.25; 0.25; ≤0.06; ≤0.06; 0.125; 0.25 MIC₉₀ (mg/L) K. pneumoniae: 1; 1; ≤0.06; ≤0.06; 0.25; 0.5
Niki et al.,⁷⁰ 2009, Japan	Clinical isolates N = 1178	Respiratory infections	Faropenem Imipenem Meropenem Doripenem Biapenem Panipenem	MIC range (mg/L) for faropenem; imipenem; meropenem; doripenem; biapenem; panipenem K. pneumoniae: 0.25–4; ≤0.06–1; ≤0.06–0.125; ≤0.06–0.25; ≤0.06–1; ≤0.06–1 MIC₅₀ (mg/L) K. pneumoniae: 0.5; 0.25; ≤0.06; ≤0.06; 0.25; 0.25 MIC₉₀ (mg/L) K. pneumoniae: 1; 0.5; ≤0.06; ≤0.06; 0.5; 0.5

AmpC, AmpC β-lactamase; CPE, carbapenemase-producing Enterobacterales; CTX-M, CTX type M variant; JSC, Japanese Society of Chemotherapy; NR, not reported.

Sample size is the total sample and includes both Enterobacterales and non-Enterobacterales strains/isolates.^bBased on susceptibility criteria for ertapenem of 2 mg/L (CLSI and EUCAST) and for meropenem of 2 mg/L for cystitis and 1 mg/L for pyelonephritis (JSC), as a substitute for faropenem.

Includes E. faecalis and Enterococcus faecium.