Global spread of Carbapenemase-producing Enterobacteriaceae

Abstract

Carbapenemases increasingly have been reported in Enterobacteriaceae in the past 10 years. Klebsiella pneumoniae carbapenemases have been reported in the United States and then worldwide, with a marked endemicity at least in the United States and Greece. Metallo-enzymes (Verona integron-encoded metallo-β-lactamase, IMP) also have been reported worldwide, with a higher prevalence in southern Europe and Asia. Carbapenemases of the oxacillinase-48 type have been identified mostly in Mediterranean and European countries and in India. Recent identification of New Delhi metallo-β-lactamase-1 producers, originally in the United Kingdom, India, and Pakistan and now worldwide, is worrisome. Detection of infected patients and carriers with carbapenemase producers is necessary for prevention of their spread. Identification of the carbapenemase genes relies mostly on molecular techniques, whereas detection of carriers is possible by using screening culture media. This strategy may help prevent development of nosocomial outbreaks caused by carbapenemase producers, particularly K. pneumoniae.

Figure 1

A) Worldwide geographic distribution of Klebsiella pneumoniae carbapenemase (KPC) producers. Gray shading indicates regions shown separately: B) distribution in the United States; C) distribution in Europe; D) distribution in China.

Figure 2

Disk diffusion antibacterial drug susceptibility testing of A) Klebsiella pneumoniae carbapenemase-2 (KPC-2)–, B) New Delhi metallo-β-lactamase-1 (NDM-1)–, and C) oxacillinase-48 (OXA-48)–producing K. pneumoniae clinical isolates. Clinical isolates producing KPC-2 and OXA-48 do not co-produce other extended-spectrum β-lactamase, but the isolate producing NDM-1 co-produces the extended-spectrum β-lactamase CTX-M-15. Wild-type susceptibility to β-lactams of K. pneumoniae includes resistance to amoxicillin, ticarcillin, and reduced susceptibility to piperacillin and cefalotin (data not shown).TZP, piperacillin/tazobactam; PIP, piperacillin; TIC, ticarcillin; AMX, amoxicillin; ETP, ertapenem; TCC, ticarcillin/clavulanic acid; CAZ, ceftazidime; CF, cefalotin; FOX, cefoxitin; IMP, imipenem; AMC, amoxicillin/clavulanic acid; CTX, cefotaxime; CXM, cefuroxime; MEM, meropenem; ATM, aztreonam; FEP, cefepime; CIP, ciprofloxacin; CS, colistin; NET, netilmicin; RA, rifampin; OFX, ofloxacin; TE, tetracycline; C, chloramphenicol; TM, tobramycin; NOR, norfloxacin; TGC, tigecycline; SXT, sulfamethoxazole/trimethoprim; AN, amikacin; FT, nitrofurantoin; FOS, fosfomycin; SSS, sulfamethoxazole; GM gentamicin.

Figure 3

Worldwide (A) and European (B) geographic distribution of Verona integron–encoded metallo-β-lactamase (VIM) and IMP enterobacterial producers.

Figure 4

Geographic distribution of New Delhi metallo-β-lactamase-1 producers, July 15, 2011. Star size indicates number of cases reported. Red stars indicate infections traced back to India, Pakistan, or Bangladesh, green stars indicate infections traced back to the Balkan states or the Middle East, and black stars indicate contaminations of unknown origin. (Most of the information corresponds to published data; other data are from P. Nordmann.)

Figure 5

Geographic distribution of oxacillinase-48 (OXA-48) type producers.