Klebsiella pneumoniae: Resistance, Virulence, and Epidemiology in Healthcare and Community Settings

Dear Colleagues,

Of all opportunistic pathogens, Klebsiella pneumoniae, alongside Acinetobacter baumannii, is the most important due to its capability to cause severe infections like pneumonia in ventilated patients (VAP), bloodstream infections (BSI), urinary tract infections (UTI) and wound infections in immunocompromised and mechanically ventilated patients. Higher-risk patients are those with severe underlying illnesses, implanted foreign devices, invasive procedures, malignancies and immunosuppression. In addition, it is an important causative agent of community-acquired UTIs in nursing home residents.  The clinical significance of K. pneumoniae is associated with its impressive capacity to acquire diverse resistance determinants from other species, mediated by thehorizontal spread of mobile genetic elements.

K. pneumoniae isolates harbor a plethora of various antibiotic resistance determinants, including extended-spectrum β-lactamases (ESBLs), plasmid-mediated AmpC β-lactamases (p-Amp-C) and also carbapenemases. Colistin is very often the last resort antibiotic, but the emergence of colistin resistance in K. pneumoniae limits its therapeutic use. Colistin resistance determinants are usually found in ESBL-positive and carbapenem-resistant K. pneumoniae (CRKP), resulting in a multidrug (MDR) or extensively drug-resistant phenotype (XDR). This poses a challenge to clinicians worldwide who treat these patients and a substantial threat to existing antibiotic armamentariums. The worldwide dissemination of CRKP and its drug resistance transfer poses a global public health threat.

Resistance to carbapenems in K. pneumoniae is mediated by two main mechanisms. The first involves the production of β-lactamases (p-AmpC or ESBL) with very-low-level carbapenem-hydrolyzing activity combined with decreased permeability due to porin loss or alteration. The second mechanism is attributed to carbapenem-hydrolyzing β-lactamases. Carbapenemases involved in acquired resistance to carbapenems in CRKP belong to Ambler class A serin β-lactamases (KPC, GES), class B metallo-β-lactamases (MBL) of the IMP, the VIM or NDM family and OXA-48-like β-lactamases belonging to the class D or carbapenem-hydrolyzing oxacillinases (CHDL). After the first report in Turkey in 2004, OXA-48 spread in Europe with a remarkable increase in OXA-48-producing organisms reported in many countries, with the highest rates observed in Turkey, France, and Germany. Endemic areas of OXA-48-positive K. pneumoniae are India, Middle East and North Africa. The gene encoding OXA-48 is plasmid-borne and located inside a composite transposon composed of two copies of the insertion sequence IS1999. The enzyme is capable of hydrolyzing penicillins and carbapenems but possesses poor activity against broad spectrum cephalosporins. Multidrug resistance in OXA-48-producing organisms often results from the coproduction of ESBLs or p-AmpC β-lactamases. Plasmid-borne fluoroquinolone resistance is usually mediated by qnr genes, which are frequently harbored by the same plasmids encoding CTX-M ESBLs.

Resistance genes in Klebsiella spp. are carried on conjugative plasmids. A formal scheme of plasmid classification is based on incompatibility (Inc) groups: plasmids with the same replication control are incompatible and cannot reside in the same cell line, whereas plasmids with different replication controls are compatible and can be propagated in the same cell. Classification is based on rep, tra and par genes, which are implicated in the replication, transfer and partitioning of the plasmids .Colistin is the last-resort antibiotic for treatment of serious infections caused by CRKP. The main mechanism of colistin resistance in K. pneumoniae is the inactivation of the mgrB gene, encoding a negative feedback regulator of the PhoQ-PhoP signaling system, which activates the pmr system responsible for addition of positively charged phosphoethanolamine and L-arabinose to negatively charged lipid A, and modifying the target for polymixins. Alternatively, the acquisition of plasmid-mediated mcr genes can result in colistin resistance.

There are new antibiotics that are being used to treat infections associated with CRKP such as ceftazidime–avibactam, ceftolozane–tazobactam or imipenem–relebactam. However, they are not efficient against MBL-producing organisms. Cefiderocol, a novel siderophore cephalosporin, is highly efficient against CRKP, but resistance to it has been reported recently, mostly with NDM-producing organisms.

Hypervirulent strains have been described recently, very frequently among CRKP. They are able to cause serious infections like bloodstream infections, meningitis or hepatic abscess in completely healthy individuals and thus pose a serious threat to public health.  We welcome manuscript submissions related to the following topics for the Special Issue:

1. Resistance mechanisms in Klebsiella pneumoniae;
2. Infections due to hypervirulent isolates;
3. Novel laboratory methods in the analysis of resistance mechanisms;
4. Therapeutic options for carbapenem-resistant Klebsiella pneumoniae;
5. Molecular epidemiology of carbapenem-resistant Klebsiella pneumoniae.

You may choose our Joint Special Issue in Microorganisms.

Dr. Branka Bedenic
Guest Editor

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• Klebsiella pneumoniae
• hypervirulent CRKP (hv-CRKP)
• carbapenemase-producing Klebsiella pneumoniae (CRKP)
• community-acquired infections
• immune evasion
• biofilm formation
• global dissemination