Treatment failure

The broadest spectrum of antiviral diugs is available against HIV. However, monotherapy with any of these diugs leads to rapid treatment failure due to selection and further evolution of resistant viruses. Since acquisition of resistance mutations requires vims replication,... 

Drug resistance in the defined sense, however, is not always the reason for treatment failures. The formation of biofilms may be as well regarded as a resistance mechanism. Cells within such a film withstand the antibiotic treatment. Some antibiotics (e.g. the aminoglycoside tobramycin) penetrate only slowly into the film. A further explanation is the existence of cells living in a non-growing, protected phenotypic state. 

A general mechanism of resistance is reducing the affinity of the antiretroviral compound for its mutant target protein. Resistance mutations associated with reduced affinity are observed during treatment failure with a fusion inhibitor, nonnucleoside reverse transcriptase inhibitors (NNRTl), integrase inhibitor, and protease inhibitors as reviewed in Chaps. 3,4, 6, and 7 (Hazuda et al. 2007 Hsiou et al. 2001 King et al. 2002 Mink et al. 2005). 

Acquired resistance. This occurs when bacteria which were previously susceptible become resistant, usually, but not always, after exposure to the antibiotic concerned. Intrirrsic resistance is always chromosomally mediated, whereas acquired resistance may occirr by mutations in the chromosome or by the acquisition of genes coding for resistance ftom an external source normally via a plasmid or transposon. Both types are clinically important and can result in treatment failure, although acquired resistance is more of a threat in the spread of antibiotic resistance (Russell Chopra 1996). 

Preexisting antimicrobial resistance is an increasing cause of treatment failure and is estimated to account for up to 70% of all treatment failures. Geography is the most important factor in HP resistance. Metronidazole-resistant strains are more prevalent in Asia (85%) than North America (30%).15 Primary resistance to amoxicillin and tetracycline remains low in both the United States and Europe. Clarithromycin resistance rates are estimated to be approximately 10% in the United States. Another confounding factor when evaluating potential antibiotic resistance is that culture and sensitivity studies are not routinely performed with HP infection. 

To assess efficacy, ask the patient whether he or she is still experiencing nausea or vomiting while using the therapy. Assess whether treatment failure is due to inappropriate medication use or the need for additional or different treatments and proceed accordingly. 

At month 3, if the viral count is still positive or fails to decrease at least 1 log, the patient is deemed a treatment failure. Reevaluate the patient for a different hepatitis B antiviral agent. 

Pentobarbital is commonly loaded at a dose of 10 to 15 mg/kg over 1 to 2 hours, followed by a continuous infusion of 0.5 to 4 mg/kg per hour. Therapy can be tapered off after 12 to 24 hours of seizure control as evident on the EEG.35 One metaanalysis reported a lower incidence of treatment failure with pentobarbital (3%) when compared to midazolam (21%) or propofol (20%), although the risk of hypotension requiring vasopressor therapy was higher when pentobarbital was used.36 This relative efficacy for pentobarbital must be considered... 

Measure plasma cortisol after surgery to determine if the patient displays persistent hypercortisol ism (surgical treatment failure) or hypocortisolism (adrenal insufficiency requiring steroid replacement therapy). 

Drug treatment failures may result from a variety of factors. Initial failure to respond to a-adrenergic antagonists occurs in 20% to 70% of treated patients. It is likely in these patients that the static factor may predominate as the cause of symptoms in these patients. Initial failure to respond to 5a-reductase inhibitors occurs in 30% to 70% of treated patients. 

It is likely that the dynamic factor may predominate as the cause of symptoms in these patients. In contrast, drug treatment failures after an initial good response to drug therapy will likely be an indication of progressive BPH disease. In such patients, surgical intervention may be indicated. 

Drug desensitization is a potentially life-threatening procedure that requires continuous monitoring in a hospital setting with suitable access to emergency treatment and intubation. It should be undertaken only under the direction of a physician with suitable training and experience. In such hands, desensitization presents less risk than treatment failure with a less effective alternative medication. 

Although their effectiveness is similar to the tetracyclines, the use of erythromycin and clindamycin is often limited due to their potential adverse outcomes. Erythromycin has treatment failure due to resistance and a high incidence of gastrointestinal intolerance, while clindamycin causes diarrhea and carries a risk of developing pseudomembranous colitis with long-term use.3,8... 

There is concern regarding administration of dexamethasone to patients with pneumococcal meningitis caused by penicillin- or cephalosporin-resistant strains, for which vancomycin would be required. Animal models indicate that concurrent steroid use reduces vancomycin penetration into the CSF by 42% to 77% and delays CSF sterilization due to reduction in the inflammatory response.23 Treatment failures have been reported in adults with resistant pneumococcal meningitis who were treated with dexamethasone, but the risk-benefit of using dexamethasone in these patients cannot be defined at this time. Animal models indicate a benefit of adding rifampin in patients with resistant pneumococcal meningitis whenever dexamethasone is used.21,23... 

Presence of middle ear effusion in the absence of symptoms is not an indicator of treatment failure. Children who complete therapy and are otherwise healthy should be reevaluated after 3 months for the presence of effusion that requires a hearing evaluation. Preschool-aged and younger children may need reexamination 3 to 6 weeks after therapy because speech and hearing impairment is more difficult to assess in this age group. 

Penicillin V 250 mg 3-4 times daily or 500 mg twice daily 250 mg 2-3 times daily 500 mg twice daily (over 12 years) 10 days Drug of choice but increasing reports of treatment failures... 

Directly observed treatment (DOT) should be used whenever possible to reduce treatment failures and the selection of drug-resistant isolates. 

Follow-up is dependent on the CSF findings. If pleocytosis is present, re-examine the CSF every 6 months until the WBC count normalizes. Consider recommending a second course of treatment if the CSF white count does not decline after 6 months or completely normalize after 2 years.15 Failure to normalize may require retreatment most treatment failures occur in immunocompromised patients. 

Treatment considerations for antiretroviral-experienced patients are much more complex than for patients who are naive to therapy. Prior to changing therapy, the reasons for treatment failure should be identified. A comprehensive review of the patient s severity of disease, antiretroviral treatment history, adherence to therapy, intolerance or toxicity, concomitant drug therapies, co-morbidities, and results of current and past HIV resistance testing should be performed. If patients fail therapy due to poor adherence, the underlying reasons must be determined and addressed prior to initiation of new therapy. Reasons for poor adherence include problems with medication access, active substance abuse, depression and/or denial of the disease, and a lack of education on the importance of 100%... 

Knowing how to prevent and treat adverse events from chemotherapy is an important aspect of patient care. Unmanaged events may result in excess morbidity and cause delays in chemotherapy administration and reduced chemotherapy doses and contribute to treatment failure. 

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