Cross Reactivity

·         Because halofantrine displays erratic bioavailability, potentially lethal cardiotoxicity, and extensive cross-resistance with mefloquine, its use generally is not recommended.

·         Resistance to melarsoprol is likely to involve transport defects, although the situation is complicated by evidence for multiple transport mechanisms of the drug. The best-characterized transporter is an unusual adenine-adenosine transporter termed the P2 transporter that has activity on melarsoprol as well as pentamidine and berenil. Cross-resistance between these compounds is observed frequently.

·         Because of the similar structures of the penicillins and cephalosporins, patients who are allergic to one class of agents may manifest cross-reactivity to a member of the other class. Immunological studies have demonstrated cross-reactivity in as many as 20% of patients who are allergic to penicillin, but clinical studies indicate a much lower frequency (about 1%) of such reactions. There are no skin tests that can reliably predict whether a patient will manifest an allergic reaction to the cephalosporins.

·         Resistance to gentamicin indicates cross-resistance to tobramycin, amikacin, kanamycin, and netilmicin because the inactivating enzyme is bifunctional and can modify all these aminoglycosides

·         Tetracycline resistance due to a ribosomal protection mechanism (tetM) produces cross-resistance to doxycycline and minocycline because the target site protected is the same for all tetracyclines.

·         Because the mechanisms producing resistance to erythromycin affect all macrolides, cross-resistance among them is complete. Macrolide-resistant strains of S. aureus are potentially cross-resistant to clindamycin and streptogramin B (quinupristin).

·         Cross-resistance between rifampin and rifabutin is common in M. tuberculosis,

·         Some foscarnet-resistant CMV isolates show cross-resistance to cidofovir.

·         Lamivudine resistance confers cross-resistance to related agents such as emtricitabine and clevudine and is often associated with an additional non-YMDD mutation that confers cross-resistance to famciclovir.

·         The reverse transcriptase insertion mutations at codon 69 produce cross-resistance to all current nucleoside analogs, including didanosine

·         The K65R substitution is associated with cross-resistance to didanosine, abacavir, and tenofovir, as well as the cytosine analogs lamivudine and emtricitabine.

·         Cross-resistance extends to all FDA-approved NNRTIs with the most common mutations. Therefore, any patient who fails treatment with one NNRTI because of a specific resistance mutation should be considered to have failed the entire class.

·         For the treatment of suspected but unconfirmed acute adrenal insufficiency, 4 mg of dexamethasone sodium phosphate can be substituted for hydrocortisone, since dexamethasone does not cross-react in the cortisol assay and will not interfere with the measurement of cortisol (either basally or in response to the cosyntropin stimulation test).

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CROSS RECTIVITY NOT SEEN IN

·         Artemisinin are not cross-resistant with other drugs; indeed, sensitivity to the artemisinins may be increased paradoxically in chloroquine-resistant parasites. When used alone, the artemisinins are associated with a high level of parasite recrudescence; the reason for this is not clear but may be related to their rapid metabolism or perhaps to a post-antibiotic-like effect on the parasite. They have gametocytocidal activity but do not affect either primary or latent liver stages.

·         Acquired resistance to sulfonamide usually does not involve cross-resistance to antimicrobial agents of other classes.

·         Aztreonam has been used successfully for the therapy of a variety of infections. One of its notable features is little allergic cross-reactivity with b-lactam antibiotics, with the possible exception of ceftazidine (Perez Pimiento et al., 1998), with which it has considerable structural similarity. Aztreonam is therefore quite useful for treating gram-negative infections that normally would be treated with a b-lactam antibiotic were it not for the history of a prior allergic reaction.

·         Linezolid inhibits protein synthesis by binding to the P site of the 50S ribosomal subunit and preventing formation of the larger ribosomal-fMet-tRNA complex that initiates protein synthesis. As mentioned above, there is no cross-resistance with other drug classes. Resistance in enterococci and staphylococci is due to point mutations of the 23S Rrna

·         Daptomycin binds to bacterial membranes resulting in depolarization, loss of membrane potential, and cell death. It has concentration-dependent bactericidal activity. Due to its unique mechanism of action, cross-resistance with other antibiotic classes seems not occur, and there are no known resistance mechanisms.

·         Mupirocin inhibits bacterial protein synthesis by reversible binding and inhibition of isoleucyl transfer-RNA synthetase. There is no cross-resistance with other classes of antibiotics.

·         cross-resistance between isoniazid and other agents used to treat tuberculosis (except ethionamide, which is structurally related to isoniazid) does not occur.

·         There is no cross-resistance between cycloserine and other tuberculostatic agents.