Binding characteristics of fluoroquinolones to synthetic levodopa melanin

To define the binding characteristics of fluoroquinolones to synthetic levodopa melanin, the binding of various drugs, including levofloxacin and ofloxacin, and positive controls (timolol and chloroquine), was investigated in-vitro. The affinity and capacity of the drug binding were calculated by Langmuir's adsorption isotherm. The affinity constant (K) and the binding capacity (r(max)) of levofloxacin were similar to those of timolol and much lower than those of chloroquine. Racemic ofloxacin and its enantiomers showed similar K and r(max), suggesting that the binding lacked stereoselectivity. The binding experiment with levofloxacin derivatives indicated that the basic nitrogen atom at position 7 of the quinolone ring, but not carboxyl group at position 3, would play a critical role in the interaction of fluoroquinolones with melanin. The melanin-drug complexes of levofloxacin and chloroquine were washed with neutral phosphate buffer, ethanol and 1 M HCl solution to explain the nature of the interaction of melanin with the drugs. Electrostatic forces mainly participate in the formation of the chloroquine-melanin complex, whereas van der Waals' and hydrophobic interactions are involved in the levofloxacin-melanin complex in addition to electrostatic forces. The interactions of various fluoroquinolones such as norfloxacin, enoxacin, sparfloxacin, ciprofloxacin and lomefloxacin with melanin were also studied. The results showed that the relative K value was: chloroquine approximately ciprofloxacin, sparfloxacin >/= lomefloxacin > timolol, levofloxacin approximately enoxacin, norfloxacin, and that the relative r(max) value was: norfloxacin, enoxacin >/= chloroquine, sparfloxacin > levofloxacin, ciprofloxacin, timolol, lomefloxacin. The fluoroquinolones vary in their affinity and capacity to bind with melanin, and ciprofloxacin and sparfloxacin showed a stronger interaction with melanin than the other fluoroquinolones studied.     

Activity of eight fluoroquinolones against methicillin-resistant Staphylococcus aureus isolated from cutaneous infections

The in vitro susceptibility of methicillin-resistant Staphylococcus aureus to eight fluoroquinolones, norfloxacin, ofloxacin, enoxacin, ciprofloxacin, lomefloxacin, sparfloxacin and nadifloxacin, was evaluated. Methicillin-resistant S. aureus strains were isolated from 64 cutaneous infections from 1991 to 1993. Nadifloxacin exhibited the lowest MIC among all of the fluoroquinolones. In addition, there was no resistance to nadifloxacin. The MIC(50) of these drugs has been increasing in the past 3 years.     

中成药中非法添加10种喹诺酮类药物的LC-MS/MS检测方法研究

摘 要 目的： 建立检查中成药和保健食品中非法添加喹诺酮类抗菌药物的专属性方法。方法: 采用液相色谱 三重四极杆质谱联用法（LC MS/MS）同时检测中成药和保健食品中非法添加的吡哌酸、诺氟沙星、环丙沙星、洛美沙星、依诺沙星、氟罗沙星、培氟沙星、司帕沙星、加替沙星、氧氟沙星10种成分,进行定性和定量分析,并进行了方法学验证。结果: 本分析方法条件下10种常被用于非法添加的喹诺酮类药物在色谱柱中得到了较好的分离,再配合二级质谱图进行定性,利用多反应监测模式的峰面积进行定量计算,专属性强,精密度良好,回收率和线性关系满足筛查需求。结论:该方法简便、准确,可以应用于中成药和保健食品中非法添加喹诺酮类化学成分的实验室筛查。     

Structure-phototoxicity relationship in Balb/c mice treated with fluoroquinolone derivatives, followed by ultraviolet-A irradiation

We examined the structure-phototoxicity relationship for fluoroquinolone antimicrobial agents (quinolones) using female albino Balb/c mice. First of all, to obtain an optimum dosage level for induction of phototoxicity, the prototype phototoxicant sparfloxacin was intravenously administered once at 10 mg/kg, 30 mg/kg or 100 mg/kg to female mice, followed immediately by ultraviolet-A (UVA) irradiation for 4 h (21.6J/cm2). The auricular thickness was measured at pre-dose (0 h), 4, 24, 48, 72 and 96 h post-dose, and then the histopathological examination of the auricle was performed. As results, the auricular thickness increased from 30 mg/kg, in conjunction with edema, cellular infiltration, epidermal necrosis and focal loss of the auricle. On the basis of these information, ciprofloxacin, enoxacin, fleroxacin, gatifloxacin, lomefloxacin, norfloxacin and ofloxacin were given intravenously to mice at a fixed dose of 100 mg/kg to compare their potential phototoxicities. Certain quinolones caused the auricular lesions in the following rank order (from lowest to highest): vehicle control (non-phototoxicity)=gatifloxacin=ofloxacin相似文献   

Sensitivities of ciprofloxacin-resistant Mycobacterium tuberculosis clinical isolates to fluoroquinolones: role of mutant DNA gyrase subunits in drug resistance

Minimum inhibitory concentrations of sitafloxacin, gatifloxacin, moxifloxacin, sparfloxacin, levofloxacin and ciprofloxacin against 59 ciprofloxacin-resistant clinical isolates of Mycobacterium tuberculosis from Japan were determined. The isolates were most susceptible to sitafloxacin and gatifloxacin. To understand better the basis for drug resistance, nucleotide sequences encoding the gyrA and gyrB quinolone resistance-determining region were determined. Predicted amino acid sequences revealed distinct mutational patterns likely to be responsible for fluoroquinolone resistance. Double gyrA mutations as well as mutations in both gyrA and gyrB correlated with increased resistance to all fluoroquinolones.     

A critical review of the fluoroquinolones: focus on respiratory infections.

The new fluoroquinolones (clinafloxacin, gatifloxacin, gemifloxacin, grepafloxacin, levofloxacin, moxifloxacin, sitafloxacin, sparfloxacin and trovafloxacin) offer excellent activity against Gram-negative bacilli and improved Gram-positive activity (e.g. against Streptococcus pneumoniae and Staphylococcus aureus) over ciprofloxacin. Ciprofloxacin still maintains the best in vitro activity against Pseudomonas aeruginosa. Clinafloxacin, gatifloxacin, moxifloxacin, sitafloxacin, sparfloxacin and trovafloxacin display improved activity against anaerobes (e.g. Bacteroides fragilis) versus ciprofloxacin. All of the new fluoroquinolones display excellent bioavailability and have longer serum half-lives than ciprofloxacin allowing for once daily dose administration. Clinical trials comparing the new fluoroquinolones to each other or to standard therapy have demonstrated good efficacy in a variety of community-acquired respiratory infections (e.g. pneumonia, acute exacerbations of chronic bronchitis and acute sinusitis). Limited data suggest that the new fluoroquinolones as a class may lead to better outcomes in community-acquired pneumonia and acute exacerbations of chronic bronchitis versus comparators. Several of these agents have either been withdrawn from the market, had their use severely restricted because of adverse effects (clinafloxacin because of phototoxicity and hypoglycaemia; grepafloxacin because of prolongation of the QTc and resultant torsades de pointes; sparfloxacin because of phototoxicity; and trovafloxacin because of hepatotoxicity), or were discontinued during developmental phases. The remaining fluoroquinolones such as gatifloxacin, gemifloxacin, levofloxacin and moxifloxacin have adverse effect profiles similar to ciprofloxacin. Extensive post-marketing safety surveillance data (as are available with ciprofloxacin and levofloxacin) are required for all new fluoroquinolones before safety can be definitively established. Drug interactions are limited; however, all fluoroquinolones interact with metal ion containing drugs (eg. antacids). The new fluoroquinolones (gatifloxacin, gemifloxacin, levofloxacin and moxifloxacin) offer several advantages over ciprofloxacin and are emerging as important therapeutic agents in the treatment of community-acquired respiratory infections. Their broad spectrum of activity which includes respiratory pathogens such as penicillin and macrolide resistant S. pneumoniae, favourable pharmacokinetic parameters, good bacteriological and clinical efficacy will lead to growing use of these agents in the treatment of community-acquired pneumonia, acute exacerbations of chronic bronchitis and acute sinusitis. These agents may result in cost savings especially in situations where, because of their potent broad-spectrum activity and excellent bioavailability, they may be used orally in place of intravenous antibacterials. Prudent use of the new fluoroquinolones will be required to minimise the development of resistance to these agents.     

Mutagenesis induced by 12 quinolone antibacterial agents in Escherichia coli WP2uvrA/pKM101.

The mutagenic potential of 12 quinolone antibacterial agents (quinolones) was examined at concentrations of 3.91-1000 ng/plate with or without S9 mix in Escherichia coli WP2uvrA/pKM101. All quinolones showed mutagenic potential in the strain: the maximum numbers of revertant colonies were observed at 7.81 ng/plate for clinafloxacin and sitafloxacin; 15.63 ng/plate for ciprofloxacin, gatifloxacin, grepafloxacin, levofloxacin, moxifloxacin, and trovafloxacin; and 31.25-500 ng/plate for enoxacin, lomefloxacin, norfloxacin and ofloxacin. The numbers for all quinolones were comparable between the groups with and without S9 mix. In all quinolones, bactericidal effects were observed at one or two higher concentrations than their mutagenic concentrations except for enoxacin without S9 mix. From these results, the WP2uvrA/pKM101 strain is proved to be highly sensitive to quinolones.     

Different mechanisms for the photoinduced production of oxidative DNA damage by fluoroquinolones differing in photostability.

Several fluoroquinolone antibacterial agents exhibit an adverse phototoxic effect in humans and are photo-cocarcinogenic in mice. The UV-induced production of reactive oxygen species plays a role in the toxicity and may be involved in carcinogenicity. Four fluoroquinolones were examined for the ability to photochemically produce oxidative damage in naked DNA. The major structural difference in the fluoroquinolones that would have an effect on their photostability is the functionality at the 8-position. At this position, 1-cyclopropyl-7-(2,8-diazbicyclo[4.3.0]non-8-yl)-6, 8-difluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid (BAY y3118) contains a chlorine atom, lomefloxacin a fluorine atom, ciprofloxacin a proton, and moxifloxacin a methoxy group. The formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo) in calf thymus DNA was assessed by HPLC with electrochemical detection, and strand breaks were measured in pBR322 with agarose gel electrophoresis. The relative photolability of the fluoroquinolones correlated to the extent of production of 8-oxodGuo and strand breaks, with both UVA and UVB irradiation, in the following order: BAY y3118 approximately lomefloxacin > ciprofloxacin > moxifloxacin. Experiments were performed to determine whether the mechanism of damage was due to a type I (radical) or type II (singlet oxygen) pathway. Nitrogen depletion of oxygen resulted in a decrease in the extent of formation of 8-oxodGuo, suggesting that oxygen was involved. The use of selective radical or singlet oxygen inhibitors was inconclusive with respect to which pathway was involved. The use of D(2)O as a solvent, which would extend the lifetime of singlet oxygen, suggested that this species is involved in the formation of 8-oxodGuo by moxifloxacin and ciprofloxacin, but not by lomefloxacin and BAY y3118. Similarly, it was found that singlet oxygen was not involved in strand break formation. Thus, the evidence suggests that fluoroquinolones can photochemically produce DNA damage by both type I and type II mechanisms.     

Compare two methods of measuring DNA damage induced by photogenotoxicity of fluoroquinolones

AIM: To compare two methods of measuring DNA damage induced by photogenotoxicity of fluoroquinolones(FQ). METHODS: Lomefloxacin (LFLX), sparfloxacin (SPFX), ciprofloxacin (CPFX), and levofloxacin (LELX)were tested by comet assay and photodynamic DNA strand breaking activity under the different conditions of UVA irradiation. RESULTS: In comet assay, photogenotoxicity was evident at SPFX 1mg/L, LFLX 5mg/L, and CPFX 5mg/L, and LELX 10mg/L. In photodynamic DNA srand-breaking activity, SPFX and LFLX induced the conver sion of the supercoiled form into the nicked relaxed form at 10-50μmol/L, while CPFX at 25μmol/L and LELX at 50μmol/L. CONCLUSION: There were good correlations between the two methods to detect DNA damage induced by phototoxicity of fluoroquinolones. Photodynamic DNA strand breaking activity was a good method to detect DNA damage induced by photogenotoxicity of fluoroquinolones as well as comet assay.     

Possible relationship between phototoxicity and photodegradation of sitafloxacin, a quinolone antibacterial agent, in the auricular skin of albino mice.

We compared the phototoxic potential of the quinolone antibacterial agent sitafloxacin with those of lomefloxacin and sparfloxacin. Female BALB/c mice were given a single intravenous administration of sitafloxacin, lomefloxacin, or sparfloxacin at 10 or 40 mg/kg, followed by ultraviolet-A (UVA) irradiation for 4 h (21.6 J/cm(2)). At 10 mg/kg, all quinolones induced either none or minimum inflammation in the auricle. At 40 mg/kg, sitafloxacin induced mild phototoxic inflammation in the dermal skin, while lomefloxacin and sparfloxacin induced very severe inflammation. In particular, 2/5 animals of the lomefloxacin group showed partial necrosis in the dermis and epidermis. We then determined the time course change of sitafloxacin concentrations in serum and auricular tissue by high performance liquid chromatography. Sitafloxacin concentrations in the auricle were markedly decreased under UVA irradiation, whereas those in sera were not affected. Furthermore, we examined the severity of sitafloxacin-induced phototoxicity under varied duration of UVA irradiation. The severity of phototoxicity increased with increasing duration of UVA irradiation, and statistical analysis showed a close correlation between the severity and the decreased area under the drug concentration curve under UVA irradiation (DeltaAUC(auricle)). The severity was decreased with delay in commencement of UVA irradiation, indicating the importance of commencement time of irradiation in the experimental condition of the phototoxicity study. It might be attributed to the decrease in DeltaAUC(auricle) after administration. These results suggest that sitafloxacin possesses milder phototoxic potential than lomefloxacin or sparfloxacin and is degraded in the auricular skin under UVA irradiation, and that the severity of phototoxicity is directly proportional to the DeltaAUC(auricle).     

In vitro photogenotoxic activity of clinafloxacin: a paradigm predicting photocarcinogenicity

Fluoroquinolone antiinfective drugs exhibit phototoxic, photogenotoxic, and photocarcinogenic activities in experimental systems which may be interrelated. Clinafloxacin (CLX), a new fluoroquinolone, is a potent antiinfective agent being developed for use in life-threatening infections. While this drug has previously been demonstrated to be phototoxic, this report evaluated the photogenotoxic and photocarcinogenic potential of CLX. When Skh-1 mice were administered CLX in the presence of ultraviolet light (UVA) at the maximum tolerated dose expected for a photocarcinogenicity bioassay, induction of DNA strand breakage was noted in keratinocytes isolated from these animals. When compared with other well-studied fluoroquinolones in vitro, CLX and Lomefloxacin (LMX) were equally effective in producing chromosome damage and DNA strand breakage in Chinese hamster ovary (CHO) cells exposed to UVA. Treatment of CHO cells with CLX in the presence of UVA also resulted in hydroxyl radical formation. However, coincubation of CHO cells with CLX and various antioxidants markedly reduced hydroxyl radical formation, but inhibited photogenotoxicity only to a limited extent. Thus, while reactive oxygen species contribute to the photogenotoxic activity of CLX, other factors may be involved. Since CLX exhibits both phototoxic and photogenotoxic activity, we predict that CLX would be photocarcinogenic in vivo. The present study suggests that under conditions of human exposure, the potential risk for CLX-induced photocarcinogenicity is small.     

体外检测氟喹诺酮类药物光毒性的可靠性

目的：比较四个氟喹诺酮类抗生素的光毒性来确定体外实验的可靠性．方法：用体内Wistar大鼠光毒性实验,Balb／c小鼠光毒性实验和体外中国仓鼠V79细胞微核实验,NIH 3T3 MTT实验在不同的UVA照射条件下测定四个氟喹诺酮类抗生素的光毒性．结果：在所有实验中,司帕沙星、洛美沙星显示出较强的光毒性,与对照组相比,均有非常显著性差异(P＜0．01);环丙沙星光毒性较温和,有显著性差异(P＜0.05);诺氟沙星在体内实验中没有显示出光毒性,但在体外实验中较高剂量(10μmol/L)能产生光毒性．结论：体内外测定药物光毒性有良好的相关性,因此体外检测氟喹诺酮类药物光毒性是可靠的．     

Effect of fluoroquinolones on melanogenesis in normal human melanocytes HEMn-DP: a comparative in vitro study

Purpose: Fluoroquinolones are one of the most commonly prescribed classes of antibiotics. However, their use is often connected with high risk of phototoxic reactions that lead to various skin or eye disorders. The aim of this study was to examine the effect of ciprofloxacin, lomefloxacin, moxifloxacin and fluoroquinolone derivatives with different phototoxic potential, on the viability and melanogenesis in melanocytes.

Materials and methods: Normal human epidermal melanocytes, dark pigmented (HEMn-DP) were used as an in vitro model system. The effect of the tested antibiotics on cell viability and melanization in pigmented cells was investigated using a spectrophotometric method. The WST-1 assay was used to detect the cytotoxic effect of antibiotics.

Results: Ciprofloxacin, lomefloxacin and moxifloxacin induced the concentration-dependent loss in melanocytes viability. The values of EC₅₀ for the tested fluoroquinolone derivatives were found to be 2.0?mM for ciprofloxacin, 0.51?mM for lomefloxacin and 0.27?mM for moxifloxacin. The exposure of cells to different concentrations of the analyzed drugs resulted in decrease in melanin content and tyrosinase activity. The highest decrease was observed for lomefloxacin which may explain its high phototoxic potential in vivo. The role of melanin in the mechanism of the toxicity of fluoroquinolones was discussed and the obtained results were compared with the previously obtained data concerning light-pigmented melanocytes (HEMa-LP).

Conclusions: The results obtained in vitro suggest that the phototoxic potential of fluoroquinolones in vivo depends on specific drug–melanin interaction, the ability of drugs to affect melanogenesis as well as on the degree of melanocytes pigmentation.     

甲磺酸加替沙星与其他4种氟喹诺酮类药物对临床分离菌的体外抗菌活性比较

目的 :比较甲磺酸加替沙星与氧氟沙星、左氧沙星、环丙沙星、司帕沙星对 182株临床分离菌的体外抗菌活性。方法 :采用琼脂平板二倍稀释法测定加替沙星等 5种氟喹诺酮类药物对 182株临床试验分离菌株的最低抑菌浓度 (MIC)。结果 :加替沙星对葡萄球菌属的MIC90 比其他 4种氟喹诺酮类药物低。葡萄球菌属对加替沙星的敏感率显著高于其他4种氟喹诺酮类药物 ;对其他G 球菌的MICR 也较其他氟喹诺酮类药物低。G-杆菌中埃希菌属、肠杆菌属对加替沙星的敏感率明显高于其他 4种氟喹诺酮类药物 ,加替沙星对埃希菌属、肠杆菌属的MIC90比左氧沙星低 2倍 ,比其他 3种抗菌药物低 8倍 ;假单胞菌属、克雷伯菌属和其他G-杆菌对加替沙星的敏感率与左氧沙星的差异无统计学意义 ,与其他 3种氟喹诺酮类药物的差异有统计学意义。结论 :甲磺酸加替沙星具有广谱而强大的体外抗菌活性。     

喹诺酮类抗生素在蒸发光散射检测器中响应因子的一致性考察

目的考察不同的喹诺酮类抗生素在蒸发光散射检测器(ELSD)中的响应因子是否一致，进而评价利用ELSD迅速测定该类药物含量的可行性。方法用HPLC-ELSD法测定了几种喹诺酮类抗生素（依诺沙星、左氧氟沙星、环丙沙星、洛美沙星和加替沙星）的进样量与响应取双对数的线性方程。色谱条件：YMC-Pack ODS-AM 柱 (150 mm×4.6 mm ID，5 μm)；流动相 0.5%三乙胺水溶液(三氟醋酸调至pH 2.5)-乙腈(48∶12);流速0.6 mL·min^-1。检测器条件：漂移管温度117 ℃，气体流速3.0 L·min^-1。结果5种物质的线性方程间无显著性差异（P>0.05）。结论5种不同的喹诺酮类抗生素在ELSD中的响应因子一致，可尝试用HPLC-ELSD法建立该类药物的一类新药基准品。     

Safety profile of antimicrobial agents

Many antibiotics have been developed and used for the treatment of infectious diseases. Although they have been known to have various adverse effects, most of the mechanisms remain still unknown. New quinolones are well known to induce convulsions and their convulsant activity enhanced by concurrent administration of anti-inflammatory drugs. Each new quinolone has an individual convulsant activity with individual drug-interaction with anti-inflammatory drugs. And enoxacin, lomefloxacin and gatifloxacin have been reported to decrease blood glucose levels in a dose-depend- ent manner, but ciprofloxacin and levofloxacin had no effect on the levels. It should be important to know the safety profile of antimicrobial agents before doctors administer these agents to the patients with infectious diseases.     

Quinolone pharmacokinetics

Fluoroquinolones have broad antibacterial spectra and are active against most Gram-negative and many Gram-positive species. They exhibit excellent oral bioavailability, extensive tissue penetration, low protein binding, and a long elimination half-life. This review compares and contrasts the pharmakonetics of some quinolone antibiotics - especially pefloxacin, ciprofloxacin, enoxacin, norfloxacin, ofloxacin, fleroxacin and lomefloxacin - in terms of their adsorption, distribution, metabolism, elimination, and interactions with other drugs and with food. In addition, the pharmacokinetics of these agents in the elderly and in patients with renal or hepatic impairment is discussed. The fluoroquinolones are established as a major class of antibiotics in the treatment of infections but pharmacokinetics factors should be considered when deciding on the most appropriate of these agents to use in individual patients.     

Comparative study on salivary distribution of fluoroquinolones in rats

As a basic approach to identifying the distribution mechanism of quinolone antibiotics into saliva, salivary excretion of five fluoroquinolones, ciprofloxacin (CPFX), norfloxacin (NFLX), lomefloxacin (LFLX), ofloxacin (OFLX) and sparfloxacin (SPFX), was compared in rats. Blood, parotid and mandibular saliva were periodically collected from the anesthetized rats after bolus i.v. administration (10 mg/kg) of the quinolones. Quantification of the fluoroquinolones was performed by HPLC methods. The saliva-to-plasma unbound concentration (S/Pu) ratios of the fluoroquinolones in parotid saliva were larger than those of mandibular saliva. These five quinolones had considerably different S/Pu ratios from 0.014 to 1.497, while the S/Pu ratios theoretically calculated by the pH-partition theory were around 1.0 to 1.3, which showed no relationship to the corresponding measured ratios. Satisfactory linear correlations were observed in the plots of measured S/Pu ratios against 1-octanol-water partition coefficients of the fluoroquinolones in both types of saliva. These results indicate that fluoroquinolones possess different diffusibility in salivary distribution among the drugs and between parotid and mandibular glands. It was also clarified that the lipophilicity of the fluoroquinolones primarily determines the extent of salivary excretion.     

Quinolone antibacterial-agent-induced cutaneous phototoxicity: ear swelling reactions in Balb/c mice

The phototoxic potentials of quinolone derivatives and the possibility of free radical contribution to their phototoxicity were investigated by measuring increments in ear thickness. Balb/c mice, fasted overnight, were orally administered ofloxacin (OFLX), lomefloxacin (LMFX), enoxacin (ENX), ciprofloxacin (CPFX) and DR-3355 (the s-isomer of OFLX), and immediately exposed to ultraviolet-A light (UVA: 320-400 nm) for 4 h (21.6 joules/cm2). Measurement of ear thickness was carried out 0, 24 and 48 h after the end of irradiation. The time-course profiles of ear thickness varied with both the doses and the quinolone used, but linear dose-response curves were obtained from the data 24 h after irradiation ended. The 50% ear thickness increment-inducing doses of LMFX, ENX, OFLX, CPFX and DR-3355 were calculated as 24.8, 81.9, 428.0, 457.9 and 526.6 mg/kg, respectively. The phototoxic potential of these quinolones coincided with the data obtained previously by measuring the incidence of erythema on the ears. Pretreatment with butylated hydroxtoluene, a free radical scavenger, almost completely prevented all swelling reactions induced by the quinolones. These results suggest that the degree of phototoxicity induced by the quinolones used could depend on the balance between the generation of free radicals and the effectiveness of the defense systems against toxic radicals.     

Susceptibility of bacterial isolates from AIDS patients to six fluoroquinolones

The susceptibilities to ciprofloxacin, DR-3355 (S-(-)-ofloxacin), enoxacin, lomefloxacin, ofloxacin and PD127,391 of 69 significant bacterial isolates from HIV-positive patients at the City Hospital, Edinburgh have been determined. With the exception of the enterococci, most of the strains tested (including staphylococci, Escherichia coli and Pseudomonas aeruginosa) were susceptible to the fluoroquinolones. Ciprofloxacin was the most active of the clinically available drugs followed by ofloxacin, lomefloxacin and enoxacin. PD127,391 and DR-3355, the new fluoroquinolones tested, were at least as active as ciprofloxacin. Hence bacterial infections in AIDS patients should respond to fluoroquinolone therapy.