The role of fluoroquinolones in the management of urinary tract infections in areas with high rates of fluoroquinolone-resistant uropathogens.

Fluoroquinolones have been recommended as the drugs of choice for the empirical treatment of uncomplicated and complicated urinary tract infections (UTIs) caused by trimethoprim-sulfamethoxazole-resistant uropathogens. However, because of the increased use of both oral and parenteral fluoroquinolones for other kinds of infections, increasing rates of resistance to fluoroquinolones among the most common uropathogens have challenged this recommendation, particularly in the Asia-Pacific region. The current interpretative criteria for the in vitro susceptibility of uropathogens to some fluoroquinolones, such as levofloxacin and ciprofloxacin, are set according to their therapeutic efficacy for bloodstream infections, and are not specific to UTIs. Fluoroquinolones exhibit concentration-dependent antibacterial activity, high renal excretion, and relatively early and prolonged urinary bactericidal titers. Whether or not current interpretative criteria for the in vitro susceptibility of uropathogens to fluoroquinolones predict clinical failure in treating UTIs is still controversial. The Clinical and Laboratory Standards Institute (CLSI) has established UTI-specific breakpoints for resistance to a few fluoroquinolones. However, the application of high-dose fluoroquinolone therapy for the treatment of mild to moderate UTIs caused by isolates with higher minimum inhibitory concentrations (MICs) of several fluoroquinolones needs to be re-validated based on more relevant clinical studies, prudent pharmacokinetic/pharmacodynamic (PK/PD) considerations, and thorough study of the mutant prevention concentration of fluoroquinolones in the treatment of UTI.

Clinical and microbiological characteristics of infections caused by various Nocardia species in Taiwan: a multicenter study from 1998 to 2010.

This multicenter study in Taiwan investigated the clinical presentations of various Nocardia species infections based on 16S rRNA sequence analysis. Patients with nocardiosis in four large medical centers from 1998 to 2010 were included. A total of 100 preserved nonduplicate isolates causing human infection were identified as Nocardia species. Sequencing analysis of 16S rRNA confirmed that 35 of 36 N. asteroides isolates identified by conventional tests were non-asteroides Nocardia species, and that two of 50 N. brasiliensis isolates had also been initially misidentified. N. brasiliensis (50%) was the most common pathogen, followed by N. cyriacigeorgica (18%). In addition, several rare pathogens were identified, including N. asiatica, N. rhamnosiphila, N. abscessus, N. transvalensis, N. elegans, and N. carnea. Primary cutaneous infection was the most common presentation, noted in 55 (55%) patients, while pulmonary infection presented in 26 (26%) patients. The crude mortality rate was 6.7% (6/89), and was lowest for primary cutaneous infection (2.2%) and highest for disseminated disease and pulmonary infection (16.7%). In conclusion, N. brasiliensis and N. cyriacigeorgica were the most common pathogens causing nocardiosis in Taiwan. Molecular methods for identifying Nocardia to the species level are mandatory for better understanding the epidemiology and clinical characteristics of patients with nocardiosis.

Suboptimal therapy and clinical management of gonorrhoea in an area with high-level antimicrobial resistance.

The choice of antimicrobial agents for the treatment of gonorrhoea is critical in areas where the prevalence of drug resistance is high. This study aimed to evaluate the antibiotic treatment of gonorrhoea in endemic areas. During 1999-2004, all Neisseria gonorrhoeae infections (n = 90) were evaluated. Patients' medical records and antibiotic treatment regimens were retrospectively reviewed if their isolates were viable (n = 65). In vitro antimicrobial susceptibility of N. gonorrhoeae isolates was performed. Urethritis (89%) and pelvic inflammatory disease (42%) were the most common presentations among men (n = 53) and women (n = 12), respectively. Of 54 patients with uncomplicated N. gonorrhoeae infection, 32 of them received appropriate antibiotics, including cefuroxime (n = 20), ceftriaxone (n = 10), ciprofloxacin (n = 1) and azithromycin (n = 1) during follow-ups. Among 65 patients, 53.8% were notified to the health authority. Check-ups of other sexually transmitted diseases were carried out in only 46% of patients. Not all isolates were susceptible to penicillin, 96.9% were resistant to tetracycline and 86% were resistant to ciprofloxacin. Ceftriaxone, cefixime, spectinomycin and azithromycin were active in vitro against all isolates. In conclusion, It is crucial to develop treatment guidelines according to regional antimicrobial resistances and educational programmes to improve clinical care for genital gonococcal diseases.

Amoebiasis among patrons visiting gay saunas in Taiwan.

AIMS: This study aimed to assess the prevalence of amoebiasis among patrons visiting gay saunas in Taiwan. METHODS: A cross-sectional survey was conducted using questionnaire interview and indirect hemagglutination assays and specific Entamoeba histolytica antigen assays of blood and rectal swab specimens, respectively, among patrons visiting 10 gay saunas between September 2006 and December 2006. RESULTS: During the three-month study period, 208 blood and 120 rectal swab specimens were tested for E. histolytica infection. Amoebiasis was detected among 3.8% and 3.3% of the patrons by serologies and antigen assays, respectively. During the latest sexual encounter, more than 70% of the patrons had oral-anogenital sex, and only 20% used condoms during oral-anogenital contact. CONCLUSION: Our findings suggest that there is a potential risk of E. histolytica transmission among the patrons visiting gay saunas who do not practise safe sex consistently in Taiwan.

Mechanisms of relaxant action of S-petasin and S-isopetasin, sesquiterpenes of Petasites formosanus, in isolated guinea pig trachea.

We investigated the mechanisms of action of S-petasin and S-isopetasin, from Petasites formosanus Kitamura which is used as a folk medicine for treating hypertension, tumors, and asthma in Taiwan. The tension changes of tracheal segments were isometrically recorded on a polygraph. S-Petasin and S-isopetasin non-competitively inhibited cumulative histamine-, and carbachol-induced contractions with an exception that S-isopetasin produced a parallel, rightward shift of the concentration-response curve of carbachol in a competitive manner. S-Petasin also non-competitively inhibited cumulative Ca(2+)-induced contractions in depolarized (K+, 60 mM; histamine, 100 microM; or carbachol, 10 microM) guinea-pig tracheas. S-Isopetasin did in depolarized (K+, 60 mM) trachea too. The nifedipine (10 microM)-remaining tension of carbachol (0.2 microM)-induced precontraction was further relaxed by S-petasin or S-isopetasin, suggesting that no matter whether either blocked VDCCs or not, S-petasin or S-isopetasin may have other mechanisms of relaxant action. The relaxant effect of S-petasin or S-isopetasin was unaffected by the presence of propranolol (1 microM), 2',5'-dideoxyadenosine (10 microM), methylene blue (25 microM), glibenclamide (10 microM), N omega-nitro-L-arginine (20 microM), or alpha-chymotrypsin (1 U/ml). However, S-petasin (100-300 microM), but not S-isopetasin, significantly inhibited cAMP-, but not cGMP-dependent PDE activity of the trachealis. The above results reveal that the mechanisms of relaxant action of S-petasin and S-isopetasin may be primarily due to its non-specific antispasmodic and antimuscarinic effects, respectively.

Outcome of cephalosporin treatment for serious infections due to apparently susceptible organisms producing extended-spectrum beta-lactamases: implications for the clinical microbiology laboratory.

Although extended-spectrum beta-lactamases (ESBLs) hydrolyze cephalosporin antibiotics, some ESBL-producing organisms are not resistant to all cephalosporins when tested in vitro. Some authors have suggested that screening klebsiellae or Escherichia coli for ESBL production is not clinically necessary, and when most recently surveyed the majority of American clinical microbiology laboratories did not make efforts to detect ESBLs. We performed a prospective, multinational study of Klebsiella pneumoniae bacteremia and identified 10 patients who were treated for ESBL-producing K. pneumoniae bacteremia with cephalosporins and whose infecting organisms were not resistant in vitro to the utilized cephalosporin. In addition, we reviewed 26 similar cases of severe infections which had previously been reported. Of these 36 patients, 4 had to be excluded from analysis. Of the remaining 32 patients, 100% (4 of 4) patients experienced clinical failure when MICs of the cephalosporin used for treatment were in the intermediate range and 54% (15 of 28) experienced failure when MICs of the cephalosporin used for treatment were in the susceptible range. Thus, it is clinically important to detect ESBL production by klebsiellae or E. coli even when cephalosporin MICs are in the susceptible range (

In vitro and in vivo combinations of cefotaxime and minocycline against Aeromonas hydrophila.

The activities of cefotaxime and minocycline against Aeromonas hydrophila were investigated. Cefotaxime (4 times the MIC) plus minocycline (0.75 times the MIC) elicited an inhibitory effect for 48 h in a time-kill study, and more infected mice treated with both drugs survived (91%) than survived after treatment with cefotaxime (9%) or minocycline (44%) alone, suggesting that cefotaxime and minocycline act synergistically against A. hydrophila.

Relaxant effects of petasins in isolated guinea pig trachea and their structure-activity relationships.

In the present study, we attempted to compare four petasins, isolated from Petasites formosanus Kitamura, and to look for structure-activity relationships, which may be helpful for synthesizing more active compounds for the treatment of asthma. Four petasins, including petasin, isopetasin, S-petasin and S-isopetasin, concentration-dependently relaxed histamine (10 microM)-, carbachol (0.2 microM)-, KCl (30 mM)-, and leukotriene D4 (10 nM)-induced precontractions of isolated guinea pig trachealis. The IC50 values strongly showed that the relaxant effects of the sulfur-containing petasins, S-petasin and S-isopetasin, were more potent than those of non-sulfur-containing petasins, petasin and isopetasin. S-isopetasin, with IC50 values around 10 microM, selectively relaxed carbachol- and KCl-induced precontractions, and had almost no effects (IC50s > 300 microM) on histamine- and leukotriene D4-induced precontractions. However, S-petasin, with IC50 values about 6-9 microM, non-selectively relaxed the precontractions induced by all these contractile agents. The influence of isomerization of either petasin to isopetasin or S-petasin to S-isopetasin on the relaxant effects is not clear.

Relaxant effects of quercetin methyl ether derivatives in isolated guinea pig trachea and their structure-activity relationships.

In the present study, we attempted to compare quercetin methyl ethers and to look for the structure-activity relationships, which may be helpful for synthesizing more active compounds for the treatment of asthma. Four present and two previously studied quercetin methyl ethers concentration-dependently relaxed histamine (30 microM), carbachol (0.2 microM) and KCl (30 mM) induced precontraction. According to their IC25 values to histamine-induced precontraction, the potency order was quercetin 3,3',4,'5,7-pentamethyl ether (QPME), quercetin 3-methyl ether > quercetin, quercetin 3,4',7-trimethyl ether (ayanin) > quercetin 4'-methyl ether (tamarixetin), quercetin 3,3',4',7,-tetramethyl ether (QTME). Therefore, the methylation at 3, at 5, and at both 3 and 7 positions of the A or/and C ring of quercetin nucleus may increase their tracheal relaxant activity. However, the methylation at the 3' and at the 4' position of the B ring of quercetin nucleus may decrease their tracheal relaxant activity.

Minocycline and cefotaxime in the treatment of experimental murine Vibrio vulnificus infection.

We conducted an in vivo study with the mouse model of Vibrio vulnificus infection to evaluate the efficacies of therapy with minocycline or cefotaxime alone and in combination. V. vulnificus was introduced subcutaneously into the area over the right thigh. The inoculum size ranged from 1.0 x 10(3) to 1.2 x 10(8) CFU from experiment to experiment but was constant for all animals in the same experiment. Antibiotics were given intraperitoneally 2 h after the bacteria were inoculated. In experiments 1 to 4, the standard dose for humans was used to treat the infection, while in experiment 5, five times the standard dose for humans was used to treat the infection. In experiment 1, with a small inoculum of 5 x 10(3) CFU, all mice in the saline-treated control group and the cefotaxime-, minocycline-, and combined antibiotic-treated groups survived. In experiment 2, with a moderate inoculum of 1.2 x 10(5) CFU, all the mice in the three antibiotic-treated groups survived, while only two of nine mice in the control group survived. In experiment 3, with a large inoculum of 8.0 x 10(7) CFU, six of nine mice in the combined antibiotic-treated group survived, while only one of nine mice in the cefotaxime-treated group and none of the mice in the control and minocycline-treated groups survived. In experiment 4, with a large inoculum of 1.2 x 10(8) CFU, 8 of 20 mice in the combined antibiotic-treated group survived, while none of the 20 mice in the control group, the group treated with cefotaxime alone, and the group treated with minocycline alone survived. In experiment 5, in which mice were infected with a large inoculum of 6.6 x 10(7) CFU and treated with five times the standard human dose of antibiotics, 10 of 12 mice in the combined antibiotic-treated group survived, while only 4 of 12 mice in the minocycline-treated group, 1 of 12 mice in the cefotaxime-treated group, and none of the mice in the control group survived. In experiments 3 to 5, the difference in the survival rates between the combined antibiotic-treated and minocycline-treated groups was statistically significant (P < 0.05). These results indicate that combination therapy with cefotaxime and minocycline is distinctly more advantageous than therapy with the single antibiotic regimen for the treatment of severe experimental V. vulnificus infections.

The selective antianginal effect without changing blood pressure of butylidenephthalide in conscious rats.

Synthetic butylidenephthalide (Bdph), 60 mg/kg per os (p.o.) given 3 h prior to injection of pituitrin (4 U/kg, i.v.), significantly prevented T-wave lowering on lead II electrocardiograph in unanesthetized rats. The effective dose, 60 mg/kg, was about 1/56th of the median lethal dose (LD50, p.o.) in rats. However, Bdph (60 mg/kg, p.o.) did not affect systolic pressure and heart rate in unanesthetized rats. Therefore, Bdph, found in the rhizome of Ligusticum chuaxiong Hort. (L. wallichii Franch., Umbelliferae), appears to have selective antianginal effect without changing blood pressure and heart rate.

Mechanisms involved in the antiplatelet activity of tetramethylpyrazine in human platelets.

Tetramethylpyrazine is the active ingredient of a Chinese herbal medicine. In this study, tetramethylpyrazine was tested for its antiplatelet activities in human platelet suspensions. In human platelets, tetramethylpyrazine (0.5-1.5 mM) dose-dependently inhibited both platelet aggregation and ATP-release reaction induced by a variety of agonists (i.e., ADP, collagen, and U46619). Tetramethylpyrazine (0.5 mM) did not significantly change the fluorescence of platelet membranes labeled with diphenylhexatriene, even at the high concentration (1.5 mM). Furthermore, tetramethylpyrazine (0.5-1.5 mM) dose-dependently inhibited [3H]inositol monophosphate formation stimulated by collagen (5 microg/ml) in [3H]myoinositol loaded platelets. Tetramethylpyrazine (0.5-1.5 mM) also dose-dependently inhibited the intracellular free Ca2+ rise of Fura 2-AM loaded platelets stimulated by collagen (5 microg/ml). Moreover, tetramethylpyrazine (0.5-1.5 mM) inhibited thromboxane B2 formation stimulated by collagen. At a higher concentration (1.0 mM), tetramethylpyrazine has also been shown to influence the binding of FITC-triflavin to platelet glycoprotein IIb/IIIa complex. Triflavin, a specific glycoprotein IIb/IIIa complex antagonist purified from Trimeresurus flavoviridis venom. It is concluded that the antiplatelet activity of tetramethylpyrazine may possibly involve two pathways: 1) at a lower concentration (0.5 mM), tetramethylpyrazine is shown to inhibit phosphoinositide breakdown and thromboxane A2 formation; and 2) at a higher concentration (1.0 mM), it leads to the inhibition of platelet aggregation through binding to the glycoprotein IIb/IIIa complex.

A newly isolated antispasmodic--butylidenephthalide.

Butylidenephthalide (BdPh), ligustilide and butylphthalide were isolated and purified from neutral oil of Ligusticum wallichii Franch. Among these three, BdPh proved to be the most active in inhibiting rat uterine contractions induced by prostaglandin F2 alpha, oxytocin and ACh. In studies done to compare the effects of BdPh and papaverine (Pap), guinea pig ileum, vas deferens and taenia coli were used. BdPh inhibited contractile responses of the ileum to agonists including ACh, K+ and Ba2+ in normal Tyrode solution and to exogenous Ca2+ in high K+ (80 mM), Ca2+-free Tyrode solution, and also responses of vas deferens responses to norepinephrine. Thus, BdPh is a non-specific antispasmodic but weaker in potency than Pap. However, as the inhibitory effects of BdPh on phasic contraction (PC) and tonic contraction (TC) of preparations, including depolarized and non-depolarized ileum and taenia coli, were much the same, it is suggested that the action mechanism of BdPh may differ from that of Pap which inhibited TC more selectively than PC. It may be concluded that BdPh possesses an non-specific antispasmodic action like Pap, the mechanism of action being different from that of Pap.