During anticancer chemotherapy, which usually involves DNA alkylating or intercalating agents, the patients become at higher risk of infection due to reduction of the WBC count, and damage to physical barrier. So, it is likely for the patient to easily get infected, specially in leukemia. Why the DNA acting antineoplastic drugs don't protect him from bacterial and fungal infection, why they don't act on the DNA of these microbes as they act on human cells.
Simple answer to your question is that these microbial agents are resistant to anticancer agents. In other words only resistant forms can cause infection and the host's immune system is also compromised by the treatment.
Molecular drug designing can help you to understand this, as every drug designed, has a particular target, they are designed to be highly specific so not to harm other cells or structures. So if microorganisms do not possess the receptors or target sites for such drugs so of course there wont be any harm to the microorganisms...and also there is a wide difference structurally and chemically between microbial and human DNA...and such drugs are designed to attack purely the higher DNAs or cells....
Most alkylating agents are
bipolar, i.e. they contain two groups capable of reacting
with DNA. They can thus form bridges between a single
strand or two separate strands of DNA, interfering with
the action of the enzymes involved in DNA replication.
The cell then either dies or is physically unable to divide
or triggers apoptosis. The damage is most serious during
the S-phase, as the cell has less time to remove the
damaged fragments.
Fungal and Microbes DNA cell cycle structure are not similar to Human being.So they are not act.
Dr. Vayalil your suggestion seems interesting, but are their any supporting studies?, I hope u can share them, I would really appreciate it
Dr. Jawwad, thank u for your elaboration, but it is difficult to me to imagine how these alkylating and intercalating agents differentiate between human DNA and other organisms DNA. Their mechanism of action are targeting the DNA strands itself and regardless of the sequence; thus, as all DNAs are made of the same base pairs, they suppose to act on all of them.
Dr. Abdul Khaleque, thank u for elaborating the mechanism of action of alkylating agents. But to my knowledge, which agrees with your elaboration about their mechanism of action, they suppose to be cell cycle phase independent; thus, I think, the difference between microbes cell cycle and human cell cycle won't effect their efficacy
Dr. Juskevicius, I am exactly talking about the example u have mentioned. In my hospital, we don't have the enough facility to sufficiently isolate the leukemia patient; thus, infections is normally expected at the nadir point. However, I found it difficult to understand how the microbes survives the long exposure to chemotherapy, which seems to me more aggressive than convential antibiotics, if they are actually effective against microbes. I have to exclude the dimensioned immunity, as antibiotics are still effective. But, may be it is the adminstration scedule, u mentioned, that have this effect.
Several antineoplastic agents do have antimicrobial effect. See for instance this article below. That the drugs lack clinical significance as antimicrobials can have many explanations the most obvious being that at the time of highest infection risk the drugs have already been excreted,
J Clin Pathol. 1993 Dec; 46(12): 1124–1125.
PMCID: PMC501725
Antimicrobial activity of cytotoxic drugs may influence isolation of bacteria and fungi from blood cultures.
V Peiris and B A Oppenheim
Abstract
The potential antimicrobial activity of cyclophosphamide, vincristine, and adriamycin against Gram positive and negative bacteria and Candida albicans was examined. The time taken for different microbial inocula to turn a simulated blood culture positive in the presence of different concentrations of these drugs was measured. Doxorubicin retarded the growth of Staphylococcus aureus, Staphylococcus epidermidis, and Streptococcus sanguis in a concentration dependent manner. Cyclophosphamide and vincristine showed minimal antimicrobial activity. Escherichia coli and Pseudomonas aeruginosa were unaffected by any of the drugs. An inoculum dependent effect was seen with some combinations of microbial inocula and cytotoxic drug concentrations.
Thank you Dr. Abrahamsson; your answer and the abstract, u have shared, pretty much resolve my inquiry.
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