The epidemiology and treatment of infections in cancer patients

Maschmeyer, Georg; Haas, Antje

doi:10.1016/j.ijantimicag.2007.06.014

Cited by 61 publications

(43 citation statements)

References 35 publications

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“…These results therefore provide knowledge of susceptibility profile and resistance mechanisms and thus can contribute to the strategic formulation of hospital infection control plans and the rational use of antimicrobials, reducing mortality from infection levels in cancer patients. frequency and severity of infections may be related to the use of potent cytotoxic drugs and increasingly invasive diagnostic tools (Maschmeyer & Haas, 2008;Wang et al, 2011). …”

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Detection of bla SPM-1, bla KPC, bla TEM and bla CTX-M genes in isolates of Pseudomonas aeruginosa, Acinetobacter spp. and Klebsiella spp. from cancer patients with healthcare-associated infections

Jácome

Alves

Jácome-Júnior

et al. 2016

Journal of Medical Microbiology

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Pseudomonas aeruginosa, Acinetobacter spp. and Klebsiella spp. are three of the pathogens most frequently involved in infections of cancer patients, and the production of b-lactamases is a major mechanism of resistance due to its wide diversity of existing enzymes. Therefore, the aim of the present study was to investigate the microbiological profile and data related to patients and infections, and to search for b-lactamase genes in bacterial isolates from hospitalized cancer patients in a hospital in Recife, Pernambuco, Brazil. A total of 169 isolates were recovered between 2012 and 2014, of which 58 were P. aeruginosa, 36 were Acinetobacter spp. and 75 were Klebsiella spp. A high percentage of carbapenem resistance was observed in P. aeruginosa and Acinetobacter spp. Among the carbapenem-resistant bacteria, the bla SPM-1 gene was detected in P. aeruginosa (35.5 %) and Acinetobacter spp. (3.8 %), while bla KPC was detected in P. aeruginosa (25.8 %) only. Among the third-and fourth-generation cephalosporin-resistant strains, in Klebsiella spp. we detected the genes bla TEM (30.6 %), bla CTX-M (58.3 %) and bla KPC (5.6 %), and in Acinetobacter spp. only bla TEM (25.9 %). This the first report of an Acinetobacter baumannii bla SPM-1 gene carrier that has been isolated in Brazil. The most frequent cancer types were bowel tumour [14.8 %; 95 % confidence interval (CI 95 % ) 9.8-21.1 %], breast cancer (13.6 %; CI 95 % 8.8-19.7 %) and prostate cancer (11.2%; CI 95 % 6.9-17.0 %). These results therefore provide knowledge of susceptibility profile and resistance mechanisms and thus can contribute to the strategic formulation of hospital infection control plans and the rational use of antimicrobials, reducing mortality from infection levels in cancer patients. frequency and severity of infections may be related to the use of potent cytotoxic drugs and increasingly invasive diagnostic tools (Maschmeyer & Haas, 2008;Wang et al., 2011). INTRODUCTIONGiven this vulnerability among patients with cancer, this population is more susceptible to community and healthcare-associated infections (HAIs). According to a recent survey by the Centers for Disease Control and Prevention (CDC), one in 25 hospitalized patients [4.0 %; 95 % confidence interval (CI 95 % ), 3.7-4.4] is battling an HAI, defined as those infections acquired in hospital or healthcare service unit that first appear 48 h or more after hospital admission or within 30 days after discharge following in-patient care (Revelas, 2012;Magill et al., 2014). Other causes for concern in many healthcare centres for patients with cancer are the high bacterial resistance rates and the rise of opportunistic multidrug-resistant (MDR) pathogens such as Pseudomonas aeruginosa and Acinetobacter baumannii (Pongas et al., 2012;Fukuta et al., 2013;Marín et al., 2014).Gram-positive bacteria are described as the most frequent cause of HAIs in cancer patients, especially through bloodstream infection (Wisplinghoff et al., 2003;Maschmeyer & Haas, 2008;Wang et al., 2011; Kosmidis & Chandrasekar...

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Detection of bla SPM-1, bla KPC, bla TEM and bla CTX-M genes in isolates of Pseudomonas aeruginosa, Acinetobacter spp. and Klebsiella spp. from cancer patients with healthcare-associated infections

Jácome

Alves

Jácome-Júnior

et al. 2016

Journal of Medical Microbiology

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“…Immunocompromised patients, such as cancer patients with severe neutropenia (18) and patients in the postoperative period following organ transplantation (2), are typically administered antibiotics prophylactically. Following aggressive antimicrobial treatments, the normal gut microflora is disrupted, allowing the germination of C. difficile spores.…”

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Mapping Interactions between Germinants and Clostridium difficile Spores

2011

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Germination of Clostridium difficile spores is the first required step in establishing C. difficile-associated disease (CDAD). Taurocholate (a bile salt) and glycine (an amino acid) have been shown to be important germinants of C. difficile spores. In the present study, we tested a series of glycine and taurocholate analogs for the ability to induce or inhibit C. difficile spore germination. Testing of glycine analogs revealed that both the carboxy and amino groups are important epitopes for recognition and that the glycine binding site can accommodate compounds with more widely separated termini. The C. difficile germination machinery also recognizes other hydrophobic amino acids. In general, linear alkyl side chains are better activators of spore germination than their branched analogs. However, L-phenylalanine and L-arginine are also good germinants and are probably recognized by distinct binding sites. Testing of taurocholate analogs revealed that the 12-hydroxyl group of taurocholate is necessary, but not sufficient, to activate spore germination. In contrast, the 6-and 7-hydroxyl groups are required for inhibition of C. difficile spore germination. Similarly, C. difficile spores are able to detect taurocholate analogs with shorter, but not longer, alkyl amino sulfonic acid side chains. Furthermore, the sulfonic acid group can be partially substituted with other acidic groups. Finally, a taurocholate analog with an m-aminobenzenesulfonic acid side chain is a strong inhibitor of C. difficile spore germination. In conclusion, C. difficile spores recognize both amino acids and taurocholate through multiple interactions that are required to bind the germinants and/or activate the germination machinery.

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“…Prompt empirical antimicrobial treatment is mandatory for cancer patients with severe neutropenia caused by antineoplastic treatment (22) and in the postoperative period after organ transplantation (5). Unfortunately, these antimicrobial regimes also favor colonization by C. difficile (41).…”

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Kinetic Evidence for the Presence of Putative Germination Receptors in C lostridium difficile Spores

2010

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Clostridium difficile is a spore-forming bacterium that causes Clostridium difficile-associated disease (CDAD). Intestinal microflora keeps C. difficile in the spore state and prevents colonization. Following antimicrobial treatment, the microflora is disrupted, and C. difficile spores germinate in the intestines. The resulting vegetative cells are believed to fill empty niches left by the depleted microbial community and establish infection. Thus, germination of C. difficile spores is the first required step in CDAD. Interestingly, C. difficile genes encode most known spore-specific protein necessary for germination, except for germination (Ger) receptors. Even though C. difficile Ger receptors have not been identified, taurocholate (a bile salt) and glycine (an amino acid) have been shown to be required for spore germination. Furthermore, chenodeoxycholate, another bile salt, can inhibit taurocholate-induced C. difficile spore germination. In the present study, we examined C. difficile spore germination kinetics to determine whether taurocholate acts as a specific germinant that activates unknown germination receptors or acts nonspecifically by disrupting spores' membranes. Kinetic analysis of C. difficile spore germination suggested the presence of distinct receptors for taurocholate and glycine. Furthermore, taurocholate, glycine, and chenodeoxycholate seem to bind to C. difficile spores through a complex mechanism, where both receptor homo-and heterocomplexes are formed. The kinetic data also point to an ordered sequential progression of binding where taurocholate must be recognized first before detection of glycine can take place. Finally, comparing calculated kinetic parameters with intestinal concentrations of the two germinants suggests a mechanism for the preferential germination of C. difficile spores in antibiotic-treated individuals.

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The epidemiology and treatment of infections in cancer patients

Cited by 61 publications

References 35 publications

Detection of bla SPM-1, bla KPC, bla TEM and bla CTX-M genes in isolates of Pseudomonas aeruginosa, Acinetobacter spp. and Klebsiella spp. from cancer patients with healthcare-associated infections

Detection of bla SPM-1, bla KPC, bla TEM and bla CTX-M genes in isolates of Pseudomonas aeruginosa, Acinetobacter spp. and Klebsiella spp. from cancer patients with healthcare-associated infections

Mapping Interactions between Germinants and Clostridium difficile Spores

Kinetic Evidence for the Presence of Putative Germination Receptors in C lostridium difficile Spores

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