Prevention of the selection of resistant Staphylococcus aureus by moxifloxacin plus doxycycline in an in vitro dynamic model: an additive effect of the combination

Firsov, Alexander A.; Vostrov, Sergey N.; Lubenko, Irene Yu; Portnoy, Yury A.; Zinner, Stephen H.

doi:10.1016/j.ijantimicag.2003.11.006

Cited by 37 publications

(29 citation statements)

References 10 publications

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“…We chose the combination of doxycycline with levofloxacin because our patient was immunocompromised. Fluoroquinolones are bactericidal antibiotics that are frequently active against Mycoplasma hominis (17), a pathogen phylogenetically related to Spiroplasma; no antagonism has been described for the combination; and an additive effect in vitro against certain infections was even found (18). The clinical and microbiological resolution in our patient suggests that this regimen might be a suitable therapeutic alternative for serious systemic infections, although further clinical experience is needed to confirm our observation.…”

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confidence: 50%

First Human Systemic Infection Caused by Spiroplasma

et al. 2015

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c Spiroplasma species are organisms that normally colonize plants and insects. We describe the first case of human systemic infection caused by Spiroplasma bacteria in a patient with hypogammaglobulinemia undergoing treatment with biological diseasemodifying antirheumatic agents. Spiroplasma turonicum was identified through molecular methods in several blood cultures. The infection was successfully treated with doxycycline plus levofloxacin. CASE REPORTA 73-year-old Caucasian woman presented to the emergency room complaining of a 2-month history of intermittent fevers of up to 38°C, proximal myalgias, a frontal headache, apathy, fatigue, and progressive swelling of the limbs. Physical examination revealed bilateral conjunctival injection. Heart murmurs were not detected, and the remainder of the examination was also normal.The patient had a history of rheumatoid arthritis and for the last 10 years had been receiving continuous biological diseasemodifying antirheumatic agents for frequent flare-ups. The biologic agents used had sequentially included etanercept, rituximab, and tocilizumab. The latter had been given for the last 3 years, until it was replaced with certolizumab 3 months before admission because of inadequate pain control. Other relevant clinical data included a selective IgM deficiency diagnosed 1 year before, with undetectable serum IgM levels, and long-term cholestatic liver disease of unknown etiology. The patient lived in an urban setting, and she denied contact with plants or animals or insect bites. There was no other epidemiological or personal background of interest.On admission, her blood tests revealed microcytic anemia suggestive of chronic disease (hemoglobin concentration, 10 g/dl [reference range, 12 to 15.5 g/dl]). Acute-phase reactants were elevated, with a C-reactive protein level of 141 mg/dl (reference range, Ͻ5 mg/dl), an erythrocyte sedimentation rate of 103 mm/h (reference range, 0 to 10 mm/h), and a fibrinogen level of 768 mg/dl (reference range, 150 to 500 mg/dl). The hepatic cholestasis enzymes were increased, similar to the patient's usual levels, with a normal bilirubin concentration. Serum IgM was undetectable (Ͻ5 mg/dl [reference range, 60 to 250 mg/dl]), and levels of IgG were low (304 mg/dl [reference range, 680 to 1,530 mg/dl]). Her serum was negative for markers of autoimmunity, the usual serum tumor markers, rheumatoid factor, and anti-citrullinated peptide antibodies. Urinalysis and serum and urine electrophoresis results were unremarkable. Thoracic computed tomography (CT) revealed mild bilateral posterobasal pleural effusion with bilateral infiltrates in "frosted glass" suggestive of heart failure. Cranial, abdominal, and pelvic CT did not show abnormal findings.Two blood culture sets were drawn. Each blood culture set included an aerobic and an anaerobic bottle (Bactec 9240; BectonDickinson Diagnostic Instrument Systems). Empirical antibiotic therapy with intravenous cefuroxime was started on admission. After 48 h of incubation, the two blood culture sets became...

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First Human Systemic Infection Caused by Spiroplasma

et al. 2015

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“…Likewise, the failure of vancomycin MPCs to be significantly lowered when combined with levofloxacin or rifampicin might also result from the lower concentrations of levofloxacin and rifampicin used in combination (levofloxacin and rifampicin are both concentrationdependent antibiotics). The reason for such a phenomenon was unanimously explained as an emergence of cross resistance by Zhanel et al 32 and Firsov et al 33 Here, we give a possible explanation from another perspective. Theoretically speaking, two-step mutations would be required for mutant growth once both drugs are kept above MIC.…”

Section: Discussionmentioning

confidence: 63%

“…Surprisingly, vancomycin in combination with rifampicin (2 or 4 mg ml À1 ) or levofloxacin (2 mg ml À1 ) did not lead to significant lowering of the isolates' vancomycin MPCs in general. According to Zhanel et al 32 and Firsov et al, 33 the MPC of an antibiotic could not be lowered when combined with a partner at a relatively lower concentration. Likewise, the failure of vancomycin MPCs to be significantly lowered when combined with levofloxacin or rifampicin might also result from the lower concentrations of levofloxacin and rifampicin used in combination (levofloxacin and rifampicin are both concentrationdependent antibiotics).…”

Section: Discussionmentioning

confidence: 97%

Comparative study of the mutant prevention concentrations of vancomycin alone and in combination with levofloxacin, rifampicin and fosfomycin against methicillin-resistant Staphylococcus epidermidis

Liu

et al. 2013

J Antibiot

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No mutant-prevention concentration (MPC) with methicillin-resistant Staphylococcus epidermidis (MRSE) has been reported. The study aimed to evaluate the propensity of vancomycin individually and in combination to prevent MRSE from mutation. A total of 10 MRSE clinical isolates were included in the study. Susceptibility testing demonstrated that the susceptibility rates to vancomycin, rifampicin, levofloxacin and fosfomycin were 100, 100, 50 and 90%, respectively. The fractional inhibition concentration indices (FICI) for vancomycin combined with rifampicin, levofloxacin or fosfomycin were X1.5 but p2, X1.5 but p2, and 40.5 but p1.5, respectively, implying indifferent interactivity. The MPC with susceptible strains was determined to be the lowest antibiotic concentration inhibiting visible growth among 10 10 CFU on four agar plates (9 cm in diameter) after a 72-h incubation at 37 1C. The MPCs were 16B32, 464, X64 and 4B16 lg ml À1 for vancomycin, rifampicin, fosfomycin and levofloxacin, respectively. The vancomycin MPCs of combinations with fosfomycin (32 lg ml À1 ), levofloxacin (2 lg ml À1 ) and rifampicin (2 or 4 lg ml À1 ) were 1B4, 16B32 and 16B32 lg ml À1 , respectively. Against mutants selected by vancomycin, rifampicin, levofloxacin and fosfomycin individually, antibiotics had standard MICs of 2B4 lg ml À1 for vancomycin, 464 lg ml À1 for rifampicin, 4B8 lg ml À1 for levofloxacin and X64 lg ml À1 for fosfomycin. Thus single-step mutation can lead to resistance of MRSE to rifampicin, levofloxacin and fosfomycin, rather than non-susceptibility to vancomycin. Vancomycin-fosfomycin combination might be a superior alternative to vancomycin in blocking the growth of MRSE mutants, especially for high-organism-burden infections.

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“…Other values are 0.008-0.031 lg/mL for Chlamydia pecorum (Pudjiatmoko et al, 1998); <0.5 lg/mL for Pasteurella haemolytica (Ole-Mapenay and Mitema, 1997); 0.06-2 lg/ mL for Mycoplasma mycoides (Egwu and Aliyu, 1998) and 0.1 lg/mL for Bacillus anthracis (Brook et al, 2001). MIC values determined in human isolates were 0.016-0.5 lg/mL for Streptococcus pneumoniae (Zhanel et al, 2003, andRoss andJones, 2004); 0.064 mg/mL for Chlamydia psittaci (Suchland et al, 2003); 0.12-0.5 lg/mL for Staphylococcus aureus (Firsov et al, 2004;Ross and Jones, 2004); 0.5 lg/mL for Mycoplasma pneumoniae (Waites et al, 2003) and 1 lg/mL for Haemophilus influenzae (Koeth et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetics of doxycycline in sheep after intravenous and oral administration

Castro

Sahagún

Diez

et al. 2009

The Veterinary Journal

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The pharmacokinetics of doxycycline were investigated in sheep after oral (PO) and intravenous (IV) administration. The IV data were best described using a 2-(n = 5) or 3-(n = 6) compartmental open model. Mean pharmacokinetic parameters obtained using a 2-compartmental model included a volume of distribution at steady-state (V ss ) of 1.759 ± 0.3149 L/kg, a total clearance (Cl) of 3.045 ± 0.5264 mL/ kg/min and an elimination half-life (t 1/2b ) of 7.027 ± 1.128 h. Comparative values obtained from the 3-compartmental mean values were: V ss of 1.801 ± 0.3429 L/kg, a Cl of 2.634 ± 0.6376 mL/kg/min and a t 1/2b of 12.11 ± 2.060 h. Mean residence time (MRT 0À1 ) was 11.18 ± 3.152 h. After PO administration, the data were best described by a 2-compartment open model. The pharmacokinetic parameter mean values were: maximum plasma concentration (C max ), 2.130 ± 0.950 lg/mL; time to reach C max (t max ), 3.595 ± 3.348 h, and absorption half-life (t 1=2k 01 ), 36.28 ± 14.57 h. Non-compartmental parameter values were: C max , 2.182 ± 0.9117 lg/mL; t max , 3.432 ± 3.307 h; F, 35.77 ± 10.20%, and mean absorption time (MAT 0-1 ), 25.55 ± 15.27 h. These results suggest that PO administration of doxycycline could be useful as an antimicrobial drug in sheep.

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Prevention of the selection of resistant Staphylococcus aureus by moxifloxacin plus doxycycline in an in vitro dynamic model: an additive effect of the combination

Cited by 37 publications

References 10 publications

First Human Systemic Infection Caused by Spiroplasma

First Human Systemic Infection Caused by Spiroplasma

Comparative study of the mutant prevention concentrations of vancomycin alone and in combination with levofloxacin, rifampicin and fosfomycin against methicillin-resistant Staphylococcus epidermidis

Pharmacokinetics of doxycycline in sheep after intravenous and oral administration

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