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#1
04.08.2008, 18:34
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Исследования при молочнице
Цитата:
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#2
04.08.2008, 19:41
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В последнее время участились случаи так называемого non-albicans Candida vaginitis . Что часто является причиной безуспешной терапии обычными противогрибковыми препаратами. С целью уточнения возбудителя и эффективного лечения и требуется определять вид кандиды и ее чувствительность к тому или иному препарату.
Более того, не возбраняется также диагносцировать вид кандиды методом ПЦР. Detection of Candida species in vaginal samples in a clinical laboratory setting. Trama JP, Adelson ME, Raphaelli I, Stemmer SM, Mordechai E. Medical Diagnostic Laboratories, L.L.C, Hamilton, NJ 08690, USA. The presence of C. albicans, C. glabrata, C. parapsilosis and C. tropicalis in 3978 vaginal swabs from patients in six US states was detected by PCR amplification. [Ссылки доступны только зарегистрированным пользователям ] |
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#3
04.08.2008, 19:45
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Это понятно. Но вопрос был об определении чувствительности. Какие-то есть публикации по этому поводу? Просто никогда не слышала об определении чувствительности в таких случаях.
[Ссылки доступны только зарегистрированным пользователям ] |
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#5
04.08.2008, 20:09
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Цитата:
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#7
04.08.2008, 20:40
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Культуральное исследование проводится на среде Сабуро, чувствительность и специфичность 66-67%. Недостатки - требует достаточно времени, дорогостоящий.
Юлии Евгеньевне - спасибо за ссылки! Из отечественных публикаций: [Ссылки доступны только зарегистрированным пользователям ] |
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#8
04.08.2008, 20:47
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Снежана Владимировна, не за что, но-по моему всем ясно, что в наше время, когда имеется устойчивость многих возбудителей к тем или иным видам препаратам, то определение чувствительности - это в общем то ключевой путь к правильному лечению. Это все клиницисты знают.
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#9
04.08.2008, 20:52
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Цитата:
Antifungal resistance: current trends and clinical outcomes John R. Graybill, MD Systemic fungal infections remain very important causes of morbidity and mortality in hospitalized patients.119 There are many different fungal pathogens, but the most noteworthy ones are relatively few. Candida continues to be the fourth most common cause of nosocomial bloodstream infections in the United States, and a more common cause than any of the individual gram-negative bacterial pathogens.[120], [121] and [122] The treatment failure rate for invasive candidiasis remains high—15% to 40% depending on the series cited.[123], [124], [125] and [126] The other major cause of systemic fungal disease is Aspergillus. Aspergillus species occur in more specialized populations with high vulnerability, particularly those with human stem cell—as well as heart, lung, and liver—transplants and those with graft-versus-host disease. Aspergillosis, while not as common as candidiasis, has a mortality rate that ranges up to ≥75%.127 In addition to Candida and Aspergillus species, non-Aspergillus molds such as Zygomycetes have begun to emerge as increasingly troubling infections in high-risk patients.[128], [129] and [130] Resistance to antifungals, as with other antimicrobials, is multifactorial. Of potential relevance is whether the antifungal is microbicidal. Although polyenes and echinocandins may be fungicidal against some pathogens in vitro, no antifungal is fungicidal against any fungus in vivo. Part of the reason may be that drugs are incompletely absorbed, too highly protein bound, very poorly penetrate into tissues such as brain abscesses or lung tissue infarcted by aspergillosis, or are too rapidly cleared to have a sustained effect. Another reason is that the host greatly contributes to the effect of any antimicrobial, and host immunosuppression may severely compromise efficacy. Finally, there are organisms that just are not well understood. For example, Coccidioides immitis is susceptible in vitro to most antifungals, infects patients without known abnormalities of immune response, and has the capacity to progress and kill patients, sometimes over the course of years, despite the best medical care.[131] and [132] The remainder of this section will examine, in turn, the contributions of susceptibility testing, pharmacokinetics, immune status of the host, and pathogenesis to fungal resistance. Contribution of susceptibility testing to resistance An antifungal agent may fail to clear the mycotic infection because it simply does not have activity against the fungal pathogen involved. This can be assessed by measuring the effectiveness of the drug in vitro. In vitro susceptibility testing is becoming increasingly more firmly established for antifungals.[133] and [134] Table 2[133] and [135] summarizes the interpretative MIC breakpoints for susceptibility of mucosal and invasive Candida infections to fluconazole treatment. These were originally tentatively established by the Clinical and Laboratory Standards Institute (CLSI) (formerly the National Committee for Clinical Laboratory Standards [NCCLS]) using broth dilution techniques and later corroborated by additional studies examining the efficacy of fluconazole therapy relative to fluconazole MIC or susceptibility.133 In the original CLSI report, the data were also extrapolated to itraconazole, and tentative interpretative MIC breakpoints for itraconazole in mucosal Candida infections are also presented in Table 2.135 J.H. Rex, M.A. Pfaller, J.N. Galgiani et al. and Subcommittee on Antifungal Susceptibility Testing of the National Committee for Clinical Laboratory Standards, Development of interpretive breakpoints for antifungal susceptibility testing: conceptual framework and analysis of in vitro-in vivo correlation data for fluconazole, itraconazole, and candida infections, Clin Infect Dis 24 (1997), pp. 235–247.135 More recent studies suggest that itraconazole- and voriconazole-susceptible isolates may have a breakpoint at 1 μg/mL.136 Milligram for milligram, voriconazole is 16- to 32-fold more potent than fluconazole. However, in a very large study of 13,338 clinical isolates of Candida species (excluding Candida krusei, which has specific absolute resistance for fluconazole but not voriconazole or posaconazole), rising fluconazole MIC was closely correlated (r = 0.93) with rising voriconazole MIC.137 The practical consequences of this is that a fluconazole MIC >32 μg/mL predicts voriconazole resistance with MIC >2 μg/mL. Preliminary data suggest that posaconazole will be found to have a similar cross-resistance relation to fluconazole susceptibility.138 Correlations of fluconazole susceptibility testing with clinical response have provided general support for the CLSI MIC breakpoints and their usefulness in predicting clinical success or failure. For the entire dataset including 1,295 patient-episode-isolate events, 92% of mucosal and 77% of invasive Candida infections were successfully treated with fluconazole when in vitro testing indicated a susceptible strain (fluconazole MIC ≤8 μg/mL).133 For strains identified as susceptible–dose-dependent (SDD)—MIC 16 to 32 μg/mL—the clinical success rate was 62% for mucosal and 71% for invasive infections; for those classified as resistant (MIC ≥64 μg/mL), the clinical success rates were 41% for mucosal and 44% for invasive infections. Pharmacodynamic parameters also support the fluconazole breakpoints and, particularly, the ratio of dose to MIC (dose–MIC ratio). In vivo studies identified a ratio of area under the curve (AUC) to MIC (AUC–MIC ratio) of approximately 25 as predictive of fluconazole clinical efficacy in patients with invasive candidiasis,139 and since the AUC (in milligrams per hour per liter) for fluconazole in adults is approximately equal to the daily dose in milligrams, the dose–MIC ratio may be used as a surrogate for the AUC–MIC ratio. A daily fluconazole dose of 200 mg typically achieves a dose–MIC ratio of ≥25 for strains with an in vitro MIC of up to 8 μg/mL; the standard dose of fluconazole for candidemia in adults is 400 to 800 mg/day. Fluconazole gastrointestinal absorption is excellent, with predictable AUC. Therefore, a daily dose of 400 mg typically achieves a dose–MIC ratio well over 25 for patients with “susceptible” species, whereas a higher daily dose (800 mg for most individuals) would be required to achieve a dose–MIC ratio of ≥25 and clinical response for patients with SDD species. For patients with highly resistant isolates, it is essentially impossible to achieve a serum concentration or a daily dose that will produce the concentration needed to inhibit those organisms. Table 3 presents the results from 4 clinical studies examining the relation between fluconazole dose–MIC ratio and clinical response in patients with either mucosal or invasive candidiasis.[134], [140], [141] and 142 S.C. Lee, C.P. Fung and J.S. Huang et al., Clinical correlates of antifungal macrodilution susceptibility test results for non-AIDS patients with severe Candida infections treated with fluconazole, Antimicrob Agents Chemother 44 (2000), pp. 2715–2718. As can be seen, the results generally support a dose–MIC ratio of ≥25 as being predictive of clinical response. |
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#10
04.08.2008, 20:52
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A more detailed review of the data shows that 285 patients with mucosal candidiasis had a dose–MIC ratio >50, with >90% clinical responses. However, only 19 of 25 patients with disseminated disease had dose–MIC ratio >50, with 76% response. Although outcomes look good, this is a small skewed group compared with those who have mucosal disease. Almost all of the patients with mucosal disease had HIV infection as the only predisposing factor, but the 25 patients with deep candidiasis had many underlying conditions that could serve as predisposing factors. These disparities make these patients not quite comparable, even though the summary data would suggest that all is well and that a dose–MIC ratio of ≥25 predicts clinical response for patients with candidal infection.
Cross-resistance and susceptibility to Candida species Candida species resistant to fluconazole are frequently resistant to other triazole antifungals as well, including itraconazole, ketoconazole, and voriconazole. Candida glabrata is of particular concern because of its rising incidence and frequent resistance to triazole drugs.[119], [143] and [144] A large study found that 96 patients infected with Candida albicans (geometric mean voriconazole MIC = 0.016 μg/mL, MIC90 = 0.25 μg/mL) had a 72% successful clinical outcome, whereas 47 patients infected with C glabrata (geometric mean voriconazole MIC = 0.794 μg/mL, MIC90 = 4 μg/mL) had only a 55% successful outcome, which was the lowest for any of the Candida species.144 Posaconazole is a newer triazole drug with broader-spectrum activity that may include invasive fungal infections refractory to other triazoles, including those caused by some species of C glabrata and by Zygomycetes.145 Resistance of Candida species to fluconazole or other triazoles is primarily owing to the upregulation of efflux pumps; to amino acid substitutions or upregulation of ERG11, the cellular binding site for triazoles; and less often to alterations in the ergosterol biosynthetic pathway.[146] and [147] Triazole efflux is mediated by specific members of the adenosine triphosphate–binding cassette (ABC) transporter family (CDR1 and CDR2, as well as CgCDR1 for C glabrata) and the major facilitator MDR1, whose activity is restricted to fluconazole. Triazole cross-resistance for Candida species, therefore, may be a function of upregulation of CDR1 or CDR2 transporters, ERG11 mutations resulting in lowered affinity, or increased levels of ERG11. Individual Candida isolates may have multiple mechanisms coexisting in the same cell line. Among echinocandins, caspofungin, the only agent for which agreement exists regarding breakpoints, exhibits excellent activity against most Candida species, with the exception of C parapsilosis, where the MIC90 was 2 μg/mL.148 The MIC90 of 2 μg/mL with caspofungin for C parapsilosis is somewhat troubling, but this organism has relatively lower virulence and, in the randomized large trials that have been done, there has not really been any hard evidence that C parapsilosis is systemically responding less well to the echinocandins than do the other species of Candida.149 Recent data from the Fungus Testing Laboratory at the University of Texas in San Antonio may shed some light on the shifting susceptibilities of C glabrata to triazoles and other antifungals. Caspofungin MIC50 (0.125 μg/mL) and MIC90 (0.25 μg/mL) values for C glabrata (N = 1,028 isolates) were generally encouraging and suggested susceptibility, as did the MIC50 (0.25 μg/mL) and MIC90 (0.5 μg/mL) values for amphotericin B (N = 1,138). Conversely, the MIC90 for fluconazole was 64 μg/mL (N = 1,535), up from the 32 μg/mL reported in the 2003 study from the same university and indicative of resistant strains. Of even greater concern, whereas the MIC90 for voriconazole was 1 μg/mL in the earlier study, it was 4 μg/mL (N = 781) in this more recent report. In addition, >2% of the C glabrata isolates were associated with a caspofungin MIC90 of >4 μg/mL, and mice infected with these isolates required greater concentrations of caspofungin to reduce tissue burden.[150] and [151] It is unclear whether this will translate into a clinical problem but, nonetheless, it is of concern. Another large study (6,970 isolates from >200 medical centers worldwide) obtained a measure of cross-resistance by assessing the in vitro activities of itraconazole, voriconazole, and other antifungals stratified by Candida species and fluconazole susceptibility.152 Fluconazole-susceptible strains of C albicans and C glabrata were also susceptible to the other agents examined. On the other hand, in the intermediate group, only 11% of C albicans strains identified as fluconazole-SDD and 0% labeled as fluconazole-resistant strains were susceptible to itraconazole, demonstrating a high degree of cross-resistance. Voriconazole susceptibility remained high for fluconazole-SDD strains of C albicans (93% susceptible) and C glabrata (97%), but showed reduced susceptibility for C albicans and C glabrata strains labeled as fluconazole resistant (57% and 13% susceptibility, respectively).152 Differences in the molecular structures and binding attributes of the different triazoles probably contribute to their varied resistance profiles to different strains of C albicans and non–C albicans species,153 as well as the contributions of other resistance mechanisms, such as the presence of MDR1, which demonstrates selectivity for fluconazole among the triazoles. As discussed, some studies suggest that the in vitro effectiveness of voriconazole for C glabrata may have decreased in recent years, and the next obvious question becomes, Does this translate into reduced efficacy in vivo? A recent study that examined the correlation between voriconazole MIC and clinical outcome for Candida species proposed the following MIC breakpoints: susceptible, ≤1 μg/mL; SDD, 2 μg/mL; and resistant, ≥4 μg/mL.144 Looking at individual Candida species, the response ranges were >70% for C albicans (72%), C krusei (78%), C parapsilosis (85%), and C tropicalis (73%), but the investigator-assessed response to voriconazole therapy was only 55% for C glabrata. An earlier study called into question the value of voriconazole as salvage therapy for patients with candidiasis for whom previous fluconazole treatment had failed.154 In the study, successful outcomes were observed in 61% of patients with esophageal candidiasis, 52% with candidemia, and 46% with disseminated disease. So, although many patients responded to salvage therapy with voriconazole, a large percentage in each group did not. These data suggest that voriconazole may not be an ideal successor to prior failed fluconazole therapy in patients with candidiasis. As a final point about interpretive breakpoints between clinical success and failure, it is probably best to think of the relation between MIC and response as continuous, rather than as having sharp breakpoints between clinical success and failure, where a MIC above the breakpoint automatically spells clinical failure while one below indicates success. Clinical experience has illustrated that patients may respond to therapy despite “resistant” isolates, although, of course, the odds of success are better with a low MIC than with a high one.144 M.A. Pfaller, D.J. Diekema and J.H. Rex et al., Correlation of MIC with outcome for Candida species tested against voriconazole: analysis and proposal for interpretive breakpoints, J Clin Microbiol 44 (2006), pp. 819–826. |
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#11
04.08.2008, 21:11
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Цитата:
Индусы тоже пока не рекомендуют ничего такого. |
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#12
04.08.2008, 21:14
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Там есть замечательная фраза:
Antimicrobial resistance is a growing problem that complicates the treatment of important nosocomial and community-acquired infections. Поэтому, даже если и нет рутинных, как вы говорите рекомендаций по определению чувствительности, то у врача есть голова, а в ней то, чем он думает. И если курс антимикотической терапии не помог, и клинические проявления кандидозного вагинита сохраняются, то лучше определить возбудителя и его чувствительность, чтобы добиться результата, чем опять пробовать тыкать пальцем в небо, и лечить неэффективным препаратом. |
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#13
04.08.2008, 21:16
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Цитата:
 Модерировано ВВС |
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#14
04.08.2008, 21:23
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Модерировано ВВС В приведенных мной ссылках как раз используется культуральный метод и определяется чувствительность к препаратам. И свои заключения об эффективности они делают именно на этих исследованиях.
Non-albicans Candida species are found in 10% to 20% of persons with recurrent VVC, so vaginal cultures should be obtained to confirm non-albicans species that are not as responsive to conventional therapies. CDC 2002 Guidelines for Sexually Transmitted Disease Treatment |
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#15
04.08.2008, 21:31
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Ко мне приходят детишки с кандидозным вульвовагинитами.
Ни разу не определяла чувствительность кандиды к тому или иному противогрибковому препарату. И никакого смысла в этом не вижу. Наверное, у детей причина кандидоза другая? |
Линейный вид
