Moxifloxacin in respiratory tract infections

Moxifloxacin is a fourth-generation fluoroquinolone that has been shown to be effective against respiratory pathogens, including Gram-positive (Streptococcus pneumoniae), Gram-negative (Haemophilus influenzae, Moraxella catarrhalis), and atypical strains (Chlamydia pneumoniae, Mycoplasma pneumoniae), as well as multi-drug resistant S. pneumoniae, including strains resistant to penicillin, macrolides, tetracyclines, trimethoprim/sulfamethoxazole and some fluoroquinolones. Moxifloxacin is highly concentrated in lung tissue, and has demonstrated rapid eradication rates. The bioavailability and half-life of moxifloxacin provides potent bactericidal effects at a dose of 400mg/day. The ratio of the area under the concentration-time curve to MIC of moxifloxacin is the highest among the fluoroquinolones against S. pneumoniae. The clinical efficacy of moxifloxacin has been shown in controlled studies of community-acquired pneumonia (CAP), exacerbations of chronic bronchitis (CB) and acute bacterial rhinosinusitis. Moxifloxacin has demonstrated a faster resolution of symptoms in CAP and exacerbations of CB patients compared with first-line therapy. It has also demonstrated better eradication in exacerbations of CB compared with standard therapy, in particular the macrolides. Treatment guidelines should take into account the results of clinical trials with moxifloxacin in order to establish the role of this antimicrobial in the therapeutic arsenal against respiratory tract infections.     

In vitro activity of moxifloxacin against recent community-acquired respiratory tract pathogens isolated in France: a national survey

Between February and June 2000, 2345 consecutive strains of Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Staphylococcus aureus and Klebsiella pneumoniae were isolated from 2088 adult patients suffering from community-acquired respiratory tract infections, in 97 hospital laboratories. Of the 1037 S. pneumoniae isolates, 48.3% were intermediately or highly penicillin resistant. For invasive isolates, the MIC90s of penicillin G, amoxycillin, cefuroxime, ceftriaxone, erythromycin, ofloxacin, ciprofloxacin and moxifloxacin were 2, 2, 4, 0.5, 1024, 2, 2 and 0.25 mg/l, respectively. All but one invasive strain were susceptible to moxifloxacin whereas 97.5% were susceptible to levofloxacin. The MIC90s of clinical isolates with intermediate susceptibility or high resistance to penicillin G, were 2, 2, 4, 1, 1024, 2, 2 and 0.25 mg/l. About 98.1, 97.0, and 83.1% of strains were inhibited by concentrations < or = 1 mg/l of moxifloxacin, levofloxacin and ciprofloxacin, respectively (E-test). Eight of the 1037 S. pneumoniae strains were not susceptible to moxifloxacin and had mutations in gyrA (eight strains), parC (four strains) or parE (three strains). Against H. influenzae (32.7% were beta-lactamase producers) and M. catarrhalis (96.3% were beta-lactamase producers), the MIC90s of moxifloxacin, amoxycillin and co-amoxiclav were 0.094 and 0.125 mg/l, 64 and 8 mg/l, and 1.5 and 0.25 mg/l, respectively. Against oxacillin-susceptible S. aureus and K. pneumoniae, the MIC90s of moxifloxacin were 0.125 and 0.84 mg/l respectively. Moxifloxacin had the highest in vitro activity of all antibiotics tested.     

Moxifloxacin: clinical efficacy and safety.

The activity, pharmacokinetics, pharmacodynamics, efficacy, safety, drug interactions, and dosage and administration of moxifloxacin are reviewed. Moxifloxacin is an oral 8-methoxyquinolone antimicrobial approved in December 1999 for use in the treatment of acute bacterial sinusitis, acute bacterial exacerbations of chronic bronchitis, and community-acquired pneumonia. This fluoroquinolone is active against common community-acquired respiratory pathogens (Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis), atypical pathogens, and many anaerobes. Moxifloxacin has an absolute bioavailability of 90% after oral administration and a mean elimination half-life of 12 hours. The drug is not a substrate or inhibitor of the hepatic cytochrome P-450 isoenzyme system thereby avoiding many potential drug interactions. Moxifloxacin has limited phototoxic potential. In clinical trials, moxifloxacin had clinical success rates of 88-97% and bacteriologic eradication rates of 90-97%. Reported adverse effects were primarily gastrointestinal (nausea, diarrhea) and were mild to moderate in severity. Moxifloxacin prolongs the QT interval by a mean + S.D. of 6 +/- 26 milliseconds above baseline and should be used with caution in patients with proarrhythmic conditions and avoided in patients receiving antiarrhythmia agents, such as quinidine, procainamide, amiodarone, and sotalol. The standard oral dosage is 400 mg once a day. Dosage adjustment is unnecessary in patients with renal dysfunction or mild to moderate hepatic dysfunction. Moxifloxacin is a safe and effective antimicrobial that will be useful for treating acute sinusitis, acute bacterial exacerbations of chronic bronchitis, and community-acquired pneumonia.     

Activity of daptomycin on biofilms produced on a plastic support by Staphylococcus spp

The aim of this study was to assess whether the novel lipopeptide daptomycin might be capable of disrupting or inhibiting the synthesis of biofilms produced by staphylococci. Fourteen recently isolated slime-producing methicillin-susceptible (MET-S) and methicillin-resistant (MET-R) strains (three MET-S Staphylococcus aureus, three MET-R S. aureus, three MET-S Staphylococcus epidermidis, three MET-R S. epidermidis and two vancomycin-intermediate S. aureus (VISA)) were tested. Slime formation on polystyrene plates was quantified spectrophotometrically. Daptomycin (2-64 mg/L) inhibited slime synthesis by > or =80% in MET-S strains, by 60-80% in MET-R S. aureus and by 70-95% in MET-R S. epidermidis. At 64 mg/L, biofilm synthesis decreased by 80% in the VISA isolates. Daptomycin also disrupted pre-formed biofilm: >50% breakdown of initial biofilm (5h) was observed in all strains. Disruption of mature biofilms (48 h), in terms of percentage, was more variable depending on the strain, ranging from ca. 20% in a MET-R S. epidermidis strain to almost 70% in two MET-S strains (one S. aureus and one S. epidermidis). Daptomycin at concentrations achievable during therapy promoted a statistically significant inhibition of slime synthesis (preventing biofilm building) and induced slime disruption (disaggregating its structure) both in initial and mature biofilms on a plastic support in all staphylococcal strains studied.     

Susceptibility to moxifloxacin and other antimicrobial agents of major pathogens responsible for community acquired respiratory tract infection in Poland

The in vitro activity of moxifloxacin was compared with that of other antimicrobial agents against 470 bacterial strains isolated from patients with respiratory tract infection. Bacteria studied included 110 penicillin susceptible and 110 penicillin non-susceptible Streptococcus pneumoniae, 50 strains of S. pyogenes, 120 strains of Haemophilus influenzae and 80 strains of Moraxella catarrhalis. Moxifloxacin was the most active of the antimicrobials tested.     

Bactericidal activity and postantibiotic effect of cefdinir (Cl 983, FK 482) against selected pathogens.

The bactericidal activity and the postantibiotic effect (PAE) of cefdinir (Cl 983, FK 482) (CDR), were determined against Staphylococcus aureus, Streptococcus pneumoniae, Haemophilus influenzae, Branhamella catarrhalis and Escherichia coli (5 strains each) in comparison to erythromycin (E), cotrimoxazole (SXT) and amoxicillin-clavulanic acid (AMC). Kinetic studies of kill showed that CDR was rapidly bactericidal at concentrations 2 and 4 times the minimum inhibitory concentration (MIC): a reduction of 99.9% in CFU values was observed after 6-8 h for many of the isolates tested. As expected, a PAE was observed when S. aureus was treated with CDR at MIC (range of individual values for 5 strains 0.8-1.5 h) and 4 x MIC (range 1.1-1.4 h). Moreover, CDR showed a significant PAE at both its MIC and 4 x MIC against S. pneumoniae (range 0.5-1.0 h and 0.9-1.1 h), H. influenzae (range 0.4-0.7 h and 0.4-0.8 h), B. catarrhalis (range 0.5-0.7 h and 0.65-0.95 h) and E. coli (range 0.5-0.6 h and 0.5-0.7 h). The good bactericidal activity and the significant PAE of CDR against Gram-positive and Gram-negative bacteria (including respiratory pathogens) are a promising indication for the clinical efficacy of this cephalosporin in several bacterial infections.     

Susceptibility patterns of bacterial isolates from hospitalised patients with respiratory tract infections (MOXIAKTIV Study)

The objective of this study was to determine: (i) the prevalence of resistance in current clinical isolates of Streptococcus pneumoniae, Staphylococcus aureus, Haemophilus influenzae, Moraxella catarrhalis and Klebsiella pneumoniae; (ii) the prevalence of production of extended-spectrum beta-lactamases (ESBLs) and methicillin resistance in S. aureus; and (iii) regional differences in the prevalence of ESBL production and clonality of K. pneumoniae isolates. Pathogens causing respiratory tract infections in hospitalised patients were prospectively collected from all over Germany. Drugs tested by Etest included moxifloxacin, levofloxacin, amoxicillin/clavulanic acid, cefuroxime, clarithromycin and penicillin G. ESBL production by K. pneumoniae was determined using cefotaxime/ceftazidime +/- clavulanic acid. Deutsches Institut für Normung (German Institute for Standardisation)/European Committee on Antimicrobial Susceptibility Testing (DIN/EUCAST) breakpoints were used where applicable. Overall, 1859 pathogens were analysed. For all species tested the fluoroquinolones achieved the highest overall susceptibility rate (92.8%) compared with clarithromycin (60.5%), amoxicillin/clavulanic acid (85.7%) and cefuroxime (89.6%). From 438 K. pneumoniae isolates, 13.0% produced an ESBL. The ESBL prevalence was 38.8% in Eastern Germany with a trend towards clonality in some centres, but ranged from 4.7% to 7.1% in Southern, Northern and Western Germany. Among the methicillin-susceptible S. aureus isolates, 10.1% were moxifloxacin- and levofloxacin-resistant. Of the S. pneumoniae isolates, 99.3% were moxifloxacin- and levofloxacin-susceptible, 93.9% were penicillin G-susceptible and 85.7% were clarithromycin-susceptible. With a MIC90 value (minimal inhibitory concentration for 90% of the isolates) of 0.19 mg/L, moxifloxacin was more potent than levofloxacin (MIC90 = 1 mg/L) against S. pneumoniae. Haemophilus influenzae and M. catarrhalis were almost 100% susceptible to the quinolones; 100% of the M. catarrhalis but only 4.5% of the H. influenzae strains were clarithromycin-susceptible. Moxifloxacin was the most active agent amongst the drugs tested, in particular against Gram-positive pathogens.     

Multicentre study of the in vitro evaluation of moxifloxacin and other quinolones against community acquired respiratory pathogens.

The in vitro activity of moxifloxacin was compared with that of ciprofloxacin, levofloxacin, ofloxacin and trovafloxacin against 710 strains (180 Streptococcus pneumoniae, 180 Haemophilus influenzae, 160 Moraxella catarrhalis and 190 Streptococcus pyogenes) isolated from patients with community-acquired respiratory tract infections. MIC values for moxifloxacin, trovafloxacin were 0.25/0.25, 0.03/0.03, 0.06/0.03 and 0.125/0.0125 mg/l for S. pneumoniae, H. influenzae, M. catharralis and S. pyogenes. Based upon the MIC(90) values and the MIC distributions, moxifloxacin and trovafloxacin were the most active of the quinolones tested. They showed enhanced activity against Gram-positive organisms including penicillin non susceptible S. pneumoniae strains. Moxifloxacin was also highly active against ciprofloxacin-resistant S. pneumoniae strains.     

Moxifloxacin activity against clinical isolates compared with the activity of ciprofloxacin

The activity of moxifloxacin, a new 8-methoxyquinolone, was compared in vitro with the activity of ciprofloxacin against clinical strains isolated from various sites of infection. The mode MIC values of moxifloxacin were superior to those of ciprofloxacin against Streptococcus pneumoniae, methicillin-susceptible and -resistant Staphylococcus aureus, Enterococcus spp., Escherichia coli and Acinetobacter spp., while ciprofloxacin was more active against Klebsiella pneumoniae and Pseudomonas spp. Both antibiotics had similar activity against Haemophilus influenzae, Moraxella catarrhalis and Enterobacter spp.     

In vitro susceptibility of 4903 bacterial isolates to gemifloxacin--an advanced fluoroquinolone

The in vitro activity of gemifloxacin against over 4900 bacterial isolates was determined by microbroth dilution with interpretation in accordance with NCCLS guidelines. Susceptibility results were compared with those for ciprofloxacin, gatifloxacin, levofloxacin and moxifloxacin. Gemifloxacin and the other fluoroquinolones were not affected by either beta-lactamase production or penicillin-resistance in Streptococcus pneumoniae. The MIC90 values for gemifloxacin were: S. pneumoniae 0.063 mg/l; Haemophilus influenzae 0.016 mg/l; Moraxella catarrhalis 0.008 mg/l, methicillin-susceptible Staphylococcus aureus 0.063 mg/l; methicillin-susceptible Streptococcus pyogenes 0.031 mg/l; Enterobacteriaceae 0.031-0.16 mg/l; Pseudomonas aeruginosa 4 mg/l; Neisseria meningitidis 0.008 mg/l. The MIC90 for gemifloxacin was lower than those for the other quinolones tested against S. pneumoniae (ciprofloxacin 2-4 mg/l, gatifloxacin 0.5 mg/l, levofloxacin 1-2 mg/l, moxifloxacin 0.25 mg/l). This study confirms the enhanced potent activity of gemifloxacin against Gram-positive pathogens, its broad-spectrum, Gram-negative activity and indicates that gemifloxacin is likely to have an important role in treating patients with Gram-positive and/or Gram-negative infections.     

Moxifloxacin (Bay 12-8039): a new methoxy quinolone antibacterial

Moxifloxacin (Bay 12-8039) is a new 8 methoxy quinolone antibacterial. The MIC90 values are < or = 0.25 mg/l for Streptococcus pneumoniae (irrespective of penicillin susceptibility), Haemophilus influenzae (beta-lactamase positive or negative), Morexella catarrhalis, Bordetella pertussis, Legionella sp., Mycoplasma pneumoniae, Clamydia pneumoniae, Mycobacterium tuberculosis, methicillin-sensitive Staphylococcus aureus, beta-haemolytic streptococci (macrolide-sensitive or -resistant), Listeria sp., most Enterobacteriaceae, Salmonella sp., Shigella sp., Neisseria gonorrhoeae, N. menigitidis, Pasteurella spp., Vibrio spp. and Yersinia enterocolitica. For Mycobacterium intracellularae, methicillin-resistant S. aureus (MRSA), ciprofloxacin-resistant S. aureus, Citrobacter freundii, Providencia sp., Serratia sp., P. aeruginosa and other non-fermentive Gram-negative rods, MIC90s are in the range 0.5-4 mg/l. For anaerobic bacteria species, MIC90s are also in the range 0.25-4 mg/l. Moxifloxacin is bactericidal at concentrations 2- to 4-fold higher than the MIC and is rapidly bactericidal against most common pathogen groups at concentrations achieved in serum with a 400 mg dose that is between 0.5-4 mg/l. There is a post-antibiotic effect against Gram-positive and -negative bacteria. Resistant mutants are at present difficult to select in the laboratory but in general, moxifloxacin has poorer activity against strains resistant to ciprofloxacin compared to those which are susceptible. Animal and laboratory pharmacodynamic models indicate that the MIC and area under the serum concentration time curve predict outcome. Various animal models mainly of respiratory tract infection indicate equivalent or superior results compared to existing or other developmental agents. Human pharmacokinetics in healthy volunteers indicate linear pharmacokinetics over the dose range 50-800 mg/day. A single dose of 400 mg produces a maximum serum concentration of 2.5-4.5 mg/l, half-life of 11-15 h, AUC of 25-40 mg x h/l and volume of distribution of 2.5-3.5 L/kg. Protein binding is about 50% and two metabolites have been identified (M-1 and M-2). Bioavailability is > 85% and a minority of clearance is via the kidneys. No dose modification is required in renal impairment. Extra vascular penetration, where studied, is comparable to that of other quinolones. At present undergoing clinical trials, with a focus on respiratory tract infection, it is likely that moxifloxacin will provide effective therapy for pathogens with MICs of < or = 0.25-0.5 mg/l. The safety profile in a large number of human subjects is awaited.     

莫西沙星对耐药葡萄球菌生物膜药效学研究

目的：研究莫西沙星对4株临床耐药葡萄球菌生物膜的体外药效学。方法：采用微量肉汤稀释法测定莫西沙星的最低抑菌浓度（Minimal inhibitory concentration,MIC）、最低抑制生物被膜浓度（Minimal biofilm inhibitory concentration,MBIC）和最低摧毁生物被膜浓度（minimal biofilm eradication concentration,MBEC）;测定莫西沙星对细菌生物膜形成量以及存活菌的影响;采用微量稀释棋盘法测定莫西沙星与局部用药瑞他帕林的联合抗生物膜效果。结果：莫西沙星在16~256mg/L的范围内可完全摧毁细菌生物膜;2 × MIC显著降低生物被膜的形成量;100 × MIC可显著降低生物被膜存活菌数;与瑞他帕林的联合抗生物膜分数（fractional biofilm inhibitory concentration,FBIC）均小于1.0。结论：莫西沙星对4株临床耐药葡萄球菌生物被膜具有抑制和摧毁作用,而且与局部用药瑞他帕林具有协同作用。     

口服莫西沙星与静脉用左氧氟沙星治疗慢性阻塞性肺病急性加重期的疗效比较

目的:观察莫西沙星片剂与左氧氟沙星注射液治疗慢性阻塞性肺病急性加重期(AECOPD)的疗效差异。方法:回顾性的分析216例AECOPD患者,114例使用莫西沙星片剂联合头孢他啶针剂(MOX/CEF组)抗感染治疗,102例使用左氧氟沙星注射液联合头孢他啶针剂(LVF/CEF组)抗感染治疗。观察2组患者临床疗效、细菌清除以及不良反应发生情况(ADR)。结果:2组药物治疗AECOPD患者的有效率均在80%以上,临床疗效差异无统计学意义;2组药物均能有效清除AECOPD患者常见的细菌,如肺炎链球菌、流感嗜血杆菌以及肺炎克雷伯菌等,细菌清除率无统计学差异。MOX/CEF组不良反应主要为胃部不适,LVF/CEF组发生静脉炎的几率多,2组均有中枢神经系统不良反应如兴奋、谵妄发生,多见于75岁以上高龄患者。结论:莫西沙星片剂与左氧氟沙星注射液均能作为AECOPD联合抗感染治疗的有效药物。莫西沙星片在不良反应发生率、用药方便度、价格等方面占有一定优势,因而AECOPD联合治疗中,喹诺酮类药物选择莫西沙星片剂较左氧氟沙星注射液为佳。     

Susceptibilities of bacteria isolated from patients with lower respiratory infectious diseases to antibiotics (2001)

From October 2001 to September 2002, we collected the specimen from 370 patients with lower respiratory tract infections in 16 institutions in Japan, and investigated the susceptibilities of the isolated bacteria to various antibacterial agents and antibiotics and patients' characteristics. Of 458 strains that were isolated from specimen (mainly from sputum) and assumed to be bacteria causing in inflammation, 456 strains were investigated. The breakdown of the isolated bacteria were: Staphylococcus aureus 69, Streptococcus pneumoniae 72, Haemophilus influenzae 85, Pseudomonas aeruginosa (non-mucoid) 44, P. aeruginosa (mucoid) 13, Klebsiella pneumoniae 32, Moraxella subgenus Branhamella catarrhalis 32, and others. Of 69 S. aureus strains, those with 4 micrograms/mL or more of MIC of oxacillin (methicillin-resistant S. aureus: MRSA) occupied 43.5%. Vancomycin and arbekacin showed the most potent activities against MRSA as observed in 2000. The frequency of S. pneumoniae exhibiting low sensitivity to penicillin (penicillin-intermediate S. pneumoniae: PISP + penicillin-resistant S. pneumoniae: PRSP) was 59.7% and both rates of PISP and PRSP were the highest after 1992. Carbapenems had strong activities against S. pneumoniae. Especially, panipenem and imipenem inhibited the growth of all 72 strains at 0.125 and 0.5 microgram/mL, respectively. Generally, all drugs had strong activities against H. influenzae with MIC90s of 16 micrograms/mL or less. The drug that had the strongest activity against H. influenzae was levofloxacin, which inhibited the growth of 80 of the 85 strains at 0.063 microgram/mL. Against P. aeruginosa mucoid strain, meropenem had a strong activity with MIC90 of 0.5 microgram/mL while, against non-mucoid strain, tobramycin had a strong activity with MIC90 of 2 micrograms/mL. K. pneumoniae showed good susceptibilities to all drugs except ampicillin and minocycline, and the MIC90s were 4 micrograms/mL or less. Particularly, cefmenoxime, cefpirome, and imipenem had the strongest activity (MIC90: 0.125 microgram/mL), and cefozopran had a strong activity, inhibiting the growth of all strains at 0.25 microgram/mL. Also, all drugs generally had strong activities against M. (B.) catarrhalis. MIC90s of all drugs were 4 micrograms/mL or less. The drug that had the strongest activity was minocycline and levofloxacin inhibiting all 32 strains at 0.063 microgram/mL. Most of the patients with respiratory infection were aged 70 years or older, accounting for approximately a half of the total (40.5%). As for the incidence by the diseases, bacterial pneumonia and chronic bronchitis were the highest, being noted in 39.2% and 37.3% of all the patients, respectively. The bacteria frequently isolated from the patients with bacterial pneumonia were S. aureus (19.3%) and S. pneumoniae (19.9%). In contrast, H. influenzae (22.0%) were frequently isolated from the patients with chronic bronchitis. Before the drug administration, the bacteria frequently isolated from the patients were S. pneumoniae (20.8%) and H. influenzae (21.5%). S. pneumoniae and H. influenzae decreased after the initiation of drug administration while S. aureus increased. The isolation frequency of P. aeruginosa was higher after than before the initiation of drug administration. The bacteria were frequently isolated from the patients who had already treated with cephems were S. aureus and P. aeruginosa. From the patients who had already treated with macrolides, S. pneumoniae was the most frequently isolated while S. aureus was the most frequently isolated from the patients pre-treated with quinolones.     

Pharmacokinetic, bacteriological, and clinical studies on panipenem/betamipron in children]

Pharmacokinetic, bacteriological and clinical studies were performed on panipenem/betamipron (PAPM/BP) in children. The results are summarized as follow: 1. Twelve patients with various bacterial infectious diseases were treated with PAPM/BP. Each dose was 20 mg/20 mg/kg, administered 3 times daily, in 30-minute intravenous drip infusion. Treatments were continued for 5-22 days. Clinical efficacies of PAPM/BP in 12 patients with bacterial infections (1 with suspected sepsis, 5 with pneumonia, 1 with acute maxillary sinusitis, 2 with acute otitis media, 1 with cervical abscess and 2 with urinary tract infection complexed type) were evaluated as excellent in 7, good in 4 and fair in 1, with an efficacy rate of 91.7%. Seventeen causative organisms found in 10 patients (Haemophilus influenzae in 4, Branhamella catarrhalis in 3, Streptococcus pneumoniae in 2, Pseudomonas aeruginosa in 2, Staphylococcus aureus in 1, alpha-Streptococcus in 1, Corynebacterium sp. in 1, Peptostreptococcus micros in 1 and Klebsiella pneumoniae in 2) were eradicated except 2 strains (S. aureus and P. aeruginosa) from 1 patient (patient No. 2). No adverse reactions were observed in any of the 12 patients. 2. MICs of PAPM were examined against 22 clinical isolates (H. influenzae 5, B. catarrhalis 3, alpha-Streptococcus 3, S. pneumoniae 2, Corynebacterium sp. 2, S. aureus 1, P. aeruginosa 1, P. micros 1, Enterobacter cloacae 1, Escherichia coli 1, Group D Streptococcus 1 and Staphylococcus epidermidis 1) from children with bacterial infections. PAPM showed a good antibacterial activity comparable to the activity of cefoperazone (CPZ) against S. pneumoniae strains relatively tolerant to penicillins. However, the activity of PAPM against H. influenzae was somewhat weaker than that of CPZ. 3. Pharmacokinetic studies.(ABSTRACT TRUNCATED AT 250 WORDS)     

Antimicrobial activities of sultamicillin against clinical isolates from upper respiratory tract infections

Sultamicillin (SBTPC) is a mutual prodrug in which ampicillin (ABPC) and a potent beta-lactamase inhibitor sulbactam (SBT) are ester-bound in an equimolar ratio. SBTPC is hydrolyzed during absorption after oral administration to provide ABPC and SBT for systemic circulation. In the present study, the antimicrobial activities of SBTPC against 50 isolates each of 6 species (Staphylococcus aureus, Klebsiella pneumoniae subsp. pneumoniae, Branhamella catarrhalis, Haemophilus influenzae, Streptococcus pneumoniae and Streptococcus pyogenes) of bacteria freshly obtained from upper respiratory tract infections were examined in relation to their bacterial beta-lactamase producing abilities. beta-Lactamase producing strains were identified using the acidometry disc method with benzylpenicillin (PCG) of cefazolin (CEZ) as a substrate, and their frequencies of appearance were calculated as follows: S. aureus 86%; K. pneumoniae subsp. pneumoniae 100%; B. catarrhalis 68%; H. influenzae 24%. Fourteen per cent of S. aureus strains examined were beta-lactamase positive using both PCG and CEZ acidometry discs. SBTPC, however, demonstrated excellent antimicrobial activities even against these beta-lactamase producing strains. Good activities were observed especially against those bacterial strains producing penicillinase (PCase). Average MIC80 values of SBTPC were 3.13 micrograms/ml for S. aureus and K. pneumoniae subsp. pneumoniae, 0.39 micrograms/ml for B. catarrhalis and H. influenzae, 0.05 micrograms/ml for S. pneumoniae and 0.025 micrograms/ml for S. pyogenes. As SBTPC was shown to possess excellent antimicrobial activities against PCase producing strains, the enhancement in activities of SBTPC compared to ABPC alone can be attributed to the inhibition of beta-lactamase by SBT which, as noted above, is a component of SBTPC in an equimolar ratio to ABPC.     

Susceptibilities of clinical bacterial isolates to antimicrobial agents. A study mainly focused on imipenem. Reported by the Research Group for Testing Imipenem Susceptibility on Clinical Isolates

This study was conducted to investigate susceptibilities of clinical bacterial isolates to imipenem (IPM) and other antibacterial agents at 64 hospital laboratories throughout Japan from September to December of 1988. In this study, identification and susceptibility testing were carried out at each laboratory and the tests were performed according to the disk dilution method recommended by NCCLS in which susceptibilities are classified into "S", "MS", "I" and "R". IPM showed markedly high in vitro activities against Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus agalactiae, Enterococcus faecalis, Haemophilus influenzae, Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Enterobacter aerogenes, Enterobacter cloacae, Serratia marcescens, Salmonella spp., Citrobacter freundii, Proteus mirabilis, Proteus vulgaris, Morganella morganii, Providencia rettgeri, Providencia stuartii, Acinetobacter calcoaceticus, Moraxella (Branhamella) catarrhalis, Alcaligenes spp., Peptococcus spp./Peptostreptococcus spp., Bacteroides fragilis and Bacteroides spp. IPM also had strong activities against Achromobacter xylosoxidans and Pseudomonas aeruginosa, but less active against Flavobacterium spp., E. faecium, coagulase-negative staphylococci (CNS), Staphylococcus aureus and Pseudomonas cepacia. In a study in which activities of IPM against bacteria isolated from different clinical sources were compared, differences in susceptibilities were observed among S. aureus, CNS, A. calcoaceticus and P. aeruginosa, but such differences were not apparent among S. pneumoniae, E. faecalis, H. influenzae, E. coli, K. pneumoniae, E. cloacae, C. freundii, S. marcescens or P. mirabilis.     

Moxifloxacin: a review of its clinical potential in the management of community-acquired respiratory tract infections

Moxifloxacin is an extended-spectrum fluoroquinolone which has improved coverage against gram-positive cocci and atypical pathogens compared with older fluoroquinolone agents, while retaining good activity against gram-negative bacteria. The antibacterial spectrum of moxifloxacin includes all major upper and lower respiratory tract pathogens; it is one of the most active fluoroquinolones against pneumococci, including penicillin- and macrolide-resistant strains. In in vitro studies, emergence of bacterial resistance was less common with moxifloxacin than with some other fluoroquinolones, but this requires confirmation in large-scale clinical studies. As with other fluoroquinolones, moxifloxacin achieves good penetration into respiratory tissues and fluids. It shows a low potential for drug interactions and dosage adjustment is not required for patients of advanced age or those with renal or mild hepatic impairment. The efficacy of oral moxifloxacin has been demonstrated in large, well-designed clinical trials in patients with community-acquired pneumonia, acute exacerbations of chronic bronchitis or acute sinusitis. Moxifloxacin 400 mg once daily achieved bacteriological and clinical success rates of approximately 90% or higher. It was as effective as, or more effective than, comparators including clarithromycin, cefuroxime axetil and high dose amoxicillin in these trials. The most commonly reported adverse events in patients receiving moxifloxacin are gastrointestinal disturbances. Moxifloxacin is also associated with QTc prolongation in some patients; there are, as yet, no data concerning the possible clinical sequelae of this effect in high-risk patients. Moxifloxacin has a low propensity for causing phototoxic reactions relative to other fluoroquinolones, and animal data suggest that it has a low potential for causing excitatory CNS and hepatotoxic effects. Conclusions: As an extended-spectrum fluoroquinolone, moxifloxacin offers the benefits of excellent activity against pneumococci, once daily administration and a low propensity for drug interactions. Although studies are needed regarding its tolerability in at-risk patients with QT interval prolongation, available data suggest that moxifloxacin is likely to become a first-line therapy option for the treatment of community-acquired lower respiratory tract infections, particularly in areas where drug-resistant S. pneumoniae or H. influenzae are common.     

Susceptibilities of clinical bacterial isolates to antimicrobial agents. A study mainly focused on imipenem. Research Group for Testing Imipenem Susceptibility on Clinical Isolates

We investigated susceptibilities of clinical bacterial isolates to imipenem (IPM) and other antimicrobial agents at 459 hospital laboratories throughout Japan from September to December of 1988. In this study, identification and susceptibility testing were performed at each hospital laboratory and the tests were carried out according to the 1-dilution or 3-dilution disc technique in which susceptibilities are classified into 4 grades: , ++, + and -. IPM had significantly high activity against Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus agalactiae, Neisseria gonorrhoeae, Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Enterobacter aerogenes, Enterobacter cloacae, Salmonella spp., Citrobacter freundii, Proteus mirabilis, Providencia rettgeri, Acinetobacter calcoaceticus, Moraxella catarrhalis, Alcaligenes spp., Peptococcus spp./Peptostreptococcus spp., Bacteroides fragilis and Bacteroides spp. and should slightly lower activities on coagulase-negative staphylococci (CNS), Enterococcus faecalis, Haemophilus influenzae, Serratia marcescens, Proteus vulgaris, Providencia stuartii and Pseudomonas aeruginosa than on the above mentioned bacteria. In a comparative study on activities of IPM against bacteria from different clinical sources, no remarkable differences were found due to different sources among S. pneumoniae, E. faecalis, H. influenzae, E. coli, K. pneumoniae, E. cloacae, C. freundii, P. mirabilis or A. calcoaceticus, whereas slight differences were found among Staphylococcus aureus, CNS, S. marcescens and P. aeruginosa.     

Antibacterial activity of tosufloxacin against major organisms detected from patients with respiratory infections

We determined the susceptibility of bacteria which were isolated from the patients with respiratory infections between January and October 2005, to tosufloxacin and other fluoroquinolones. A total of 900 isolate including 300 Streptococcus pneumoniae, 100 Streptococcus pyogenes, 100 Moraxella catarrhalis, 200 Haemophilus influenzae, 100 Klebsiella pneumoniae and 100 Pseudomonas aeruginosa were tested. Tosufloxacin, gatifloxacin, levofloxacin, moxifloxacin, ciprofloxacin and prulifloxacin were used as the test antimicrobials. Tosufloxacin, gatifloxacin and moxifloxacin were potent antibiotics tested for the antibacterial activity against Streptococcus including penicillin-resistant S. pneumoniae; the MIC90 were 0.12-0.5/ micromL. Fluoroquinolones exerted the potent antibacterial activity against M. catarrhalis and H. influenzae; the MIC90 of fluoroquinolones tested were < or =0.06 microg/mL. Tosufloxacin, ciprofloxacin and prulifloxacin showed to be more active against K. pneumoniae and P. aeruginosa, but parts of some strains were resistant. These results indicate that tosufloxacin has the potent antibacterial activity against major organisms detected from patients with respiratory infections. Since it was approved in 1990, tosufloxacin was considered to be useful as a therapeutic antimicrobial for the treatment of respiratory infections.