New antimicrobial agents for the treatment of bacterial infections in cancer patients

Abstract

Patients with cancer develop serious bacterial infections often, especially during periods of severe and prolonged neutropenia. Antibiotic usage for the prevention and treatment of bacterial infections in these high-risk patients leads to selection pressures resulting in the emergence and spread of resistant organisms. Many organisms acquire several resistance mechanisms, making them multi-drug-resistant (MDR) (defined as resistance to three or more different classes of antibiotics). These infections are associated with increased morbidity, mortality and costs. The development of novel antimicrobial agents with activity against pathogens that have become resistant to currently available agents is one strategy for combating resistant organisms. Several novel agents have either recently been approved, or are in various stages of development and are discussed in detail. It is unlikely that these agents will have a major impact on reducing the development and spread of MDR organisms. Consequently, the judicious use of currently available agents referred to as Antimicrobial Stewardship, and the development of and adherence to appropriate Infection Control policies and procedures are vital components in the management of these high-risk patients.

Stenotrophomonas maltophilia: an Emerging Global Opportunistic Pathogen

“…S. maltophilia is a significant pathogen in cancer patients, particularly those with obstructive lung cancer. This review will not address in detail infections of S. maltophilia in cancer patients, and the reader is directed to three recent articles that address the implications of infection by S. maltophilia in cancer patients (285,293,344).…”

“…A recent review addressed the use of new antimicrobial agents in cancer patients to treat infections of MDR bacteria, including S. maltophilia (285). There is ongoing debate about the use of monotherapy versus combination therapy to treat infections of S. maltophilia.…”

In-Vitro Antibacterial / Antifungal Screening of 2-Chloroquinoline Scaffold Derivatives

“…The 1,3,4-oxadiazole derivatives (7)(8)(9)(10) were synthesized by cyclisation of hydrazones (3-6) of isonicotinic acid hydrazide (INH) or benzoic acid hydrazide with intermediate 1 and 2 using chloramine-T as catalyst in refluxing ethanol. The 2-chloro-3-formylquinoline and 2-chloro-3-formyl-6-methylquinoline (1, 2) were further reduced to alcohol (11,12) using solid NaBH 4 in methanol and subsequent reaction of 11 or 12 with benzoyl or p-methyl benzoyl chloride in pyridine affords various benzoate derivatives (13)(14)(15)(16). The chlorination of compounds (11,12) with SOCl 2 in dry benzene afforded intermediates 3-(chloromethyl)-2-chloroquinoline (17,18) and their successive nucleophilic substitution reaction with sulphanilamide or p-aminophenol in absolute ethanol in the presence of organic base triethylamine (TEA) gave 2-chloroquinolinyl amines (19)(20)(21)(22).…”

“…The 2-chloro-3-formylquinoline and 2-chloro-3-formyl-6-methylquinoline (1, 2) were further reduced to alcohol (11,12) using solid NaBH 4 in methanol and subsequent reaction of 11 or 12 with benzoyl or p-methyl benzoyl chloride in pyridine affords various benzoate derivatives (13)(14)(15)(16). The chlorination of compounds (11,12) with SOCl 2 in dry benzene afforded intermediates 3-(chloromethyl)-2-chloroquinoline (17,18) and their successive nucleophilic substitution reaction with sulphanilamide or p-aminophenol in absolute ethanol in the presence of organic base triethylamine (TEA) gave 2-chloroquinolinyl amines (19)(20)(21)(22). While various 1 H-benzimidazol-2-ylsulfanyl)methyl (23)(24)(25)(26) derivatives were prepared by reacting intermediate (17,18) with 2-mercaptobenzimidazole or 2-mercapto-6-nitrobenzimidazole in ethanol in presence of base NaOH.…”

“…This was further supported by mass spectrum of compound 7 (m/z 309.12). The synthesis of compounds (13-16) was achieved by reacting quinoline carbinol derivatives (11,12) with benzoyl chloride in pyridine. The formation of benzoate derivatives were established by locating characteristics peak of -CH 2 OCO-which was observed in the range at δ value 5.01-5.06 ppm integrating for two protons in 1 H-NMR.…”