An old antibiotic for a new multiple-resistant Enterococcus faecium?

Moreno, Francisco; Jorgensen, James H.; Weiner, Marc

doi:10.1016/0732-8893(94)90017-5

Cited by 26 publications

(14 citation statements)

References 17 publications

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“…There are reports to suggest that tetracyclines are effective for the treatment of VREF and that outcome could be improved by their addition to Q-D (4,5,7,9,11,14). In our study, the addition of MIN may have improved the outcome in those patients with VRE infections resistant to Q-D. Future prospec- Occurrence of adverse events.…”

Section: Efficacy Of Q-d Although Q-d Is Highly Active In Vitromentioning

confidence: 83%

Treatment of Vancomycin-Resistant Enterococcal Infections in the Immunocompromised Host: Quinupristin-Dalfopristin in Combination with Minocycline

Raad

Hachem

Hanna

et al. 2001

Antimicrob Agents Chemother

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, 56 oncology patients infected with vancomycin-resistant enterococci (VRE) were treated with quinopristin-dalfopristin (Q-D) plus minocycline (MIN). Infections included bacteremia, urinary tract infection, pneumonia, and wound infection. The response rate was 68%, and the most frequent adverse event was arthralgia or myalgia (36%). Q-D-MIN is effective for VRE infection in cancer patients but is associated with a substantial frequency of arthralgia or myalgia.

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Section: Efficacy Of Q-d Although Q-d Is Highly Active In Vitromentioning

confidence: 83%

Treatment of Vancomycin-Resistant Enterococcal Infections in the Immunocompromised Host: Quinupristin-Dalfopristin in Combination with Minocycline

Raad

Hachem

Hanna

et al. 2001

Antimicrob Agents Chemother

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“…This is the first report of a clinically relevant, nonanticancer drug generating P-gp expression in a cancer cell line. Doxycycline is used for treating a variety of infectious diseases in cancer patients (29,33,44). It has also been used previously for chemical pleurodesis in patients with malignant pleural effusions (15,39) and is currently being investigated as an antiangiogenic agent for the treatment of cancer (19,23).…”

Section: Discussionmentioning

confidence: 99%

Doxycycline Induces Expression of P Glycoprotein in MCF-7 Breast Carcinoma Cells

Mealey¹,

Barhoumi

Burghardt

et al. 2002

Antimicrob Agents Chemother

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P-glycoprotein (P-gp) overexpression by tumor cells imparts resistance to multiple antineoplastic chemotherapeutic agents (multiple drug resistance). Treatment of tumor cells with chemotherapeutic agents such as anthracyclines, epipodophyllotoxins, andVinca alkaloids results in induction of P-gp expression. This study was performed to determine if clinically relevant antimicrobial drugs (i.e., drugs that are used to treat bacterial infections in cancer patients) other than antineoplastic agents can induce expression of P-gp in MCF-7 breast carcinoma cells. Expression of P-gp and MDR1 mRNA was determined in samples from MCF-7 cells that were treated in culture with doxorubicin (positive control) and the antimicrobial drugs doxycycline, piperacillin, and cefoperazone. The functional status of P-gp was assessed using laser cytometry to determine intracellular doxorubicin concentrations. The MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assay was used to determine if the cytotoxicity of experimental drugs was related to their ability to induce P-gp expression. MCF-7 cells treated with doxycycline (MCF-7/doxy) were stimulated to overexpress P-gp, whereas cells treated with piperacillin and cefoperazone did not overexpress P-gp. MCF-7/doxy cells were compared to a positive-control subline, MCF-7/Adr, previously selected for doxorubicin resistance, and to MCF-7 cells treated with doxorubicin (MCF-7/doxo). All three sublines overexpressed P-gp and MDR1 mRNA and accumulated less intracellular doxorubicin than did control MCF-7 cells. P-gp expression was induced only by experimental drugs that were cytotoxic (doxorubicin and doxycycline). Doxycycline, a drug that has been used for treatment of bacterial infections in cancer patients, can induce functional P-gp expression in cancer cells, resulting in multidrug resistance.In 1970, Biedler and Riehm (3) described an in vitro model of chemotherapeutic multidrug resistance (MDR) in which cultured cells that were selected for growth in actinomycin D developed resistance to a variety of structurally and functionally diverse cytotoxic compounds. Further studies showed that the emergence of MDR was associated with increased levels of a transmembrane glycoprotein (24), P glycoprotein (P-gp). P-gp, the product of the MDR1 gene, is a 170-kDa protein that functions as an energy-dependent drug efflux pump whose substrates include naturally occurring, lipophilic agents with a complex ring structure such as Vinca alkaloids, anthracyclines, epipodophyllotoxins, and certain rhodamine dyes (18,26,37). Exposure of tumor cells to any of these substrates can generate overexpression of P-gp, resulting in the MDR phenotype.Drug exposure is thought to cause overexpression of P-gp by both selection of resistant cells and induction of P-gp expression at the level of the MDR1 promoter (14, 34). The MDR1 promoter contains a heat-shock consensus element (46) and a putative xenobiotic response element that responds directly to treatment with cytotoxic agents (25,45), supporting th...

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“…plus gentamicin [15][16][17][18][19][20][21][22]. Reports involving small numbers of patients indicate that these agents can be successful in some cases, but clinical failures and development of resistance during treatment are common.…”

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confidence: 97%

Quinupristin/Dalfopristin Therapy for Infections Due to Vancomycin-Resistant Enterococcus faecium

Winston

Emmanouilides

Kroeber

et al. 2000

Clinical Infectious Diseases

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The efficacy and safety of quinupristin/dalfopristin for treatment of infections due to vancomycin-resistant Enterococcus faecium were evaluated in 24 hospitalized patients with documented infections (19 bacteremias, 5 localized infections) caused by vancomycin-resistant E. faecium that was susceptible to quinupristin/dalfopristin in vitro. Patients received iv quinupristin/dalfopristin at a dosage of either 7.5 mg/kg every 8 h or 5 mg/kg every 8 h. A favorable clinical response (cure or improvement) occurred in 19 (83%) of 23 evaluable patients; bacteriologic eradication occurred in 17 (74%) of 23 evaluable patients. A favorable clinical response was observed in 12 (80%) of 15 patients who were treated with 7.5 mg/kg of quinupristin/dalfopristin every 8 h and in 7 (88%) of 8 patients treated with 5 mg/kg of quinupristin/dalfopristin every 8 h. Two of four treatment failures were associated with a decrease in the in vitro susceptibility of vancomycin-resistant E. faecium to quinupristin/dalfopristin. Superinfections developed in 6 patients (26%), but only one was caused by Enterococcus faecalis that was resistant to quinupristin/dalfopristin. Myalgias and arthralgias were the only adverse events related to quinupristin/dalfopristin. These conditions occurred in 8 (33%) of 24 patients and were dose-related (8 cases in 16 patients treated with 7.5 mg/kg of quinupristin/dalfopristin every 8 h, no cases in 8 patients treated with 5 mg/kg every 8 h). Mortality associated with vancomycin-resistant E. faecium infection was 17% (4 of 23 patients), whereas mortality from other causes was 52% (12 of 23 patients). These results suggest that quinupristin/dalfopristin is effective as treatment for vancomycin-resistant E. faecium infections in critically ill patients with serious underlying conditions. Except for myalgias and arthralgias at higher dosages, the drug is well-tolerated.

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An old antibiotic for a new multiple-resistant Enterococcus faecium?

Cited by 26 publications

References 17 publications

Treatment of Vancomycin-Resistant Enterococcal Infections in the Immunocompromised Host: Quinupristin-Dalfopristin in Combination with Minocycline

Treatment of Vancomycin-Resistant Enterococcal Infections in the Immunocompromised Host: Quinupristin-Dalfopristin in Combination with Minocycline

Doxycycline Induces Expression of P Glycoprotein in MCF-7 Breast Carcinoma Cells

Quinupristin/Dalfopristin Therapy for Infections Due to Vancomycin-Resistant Enterococcus faecium

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