Cipro (Ciprofloxacin, ciprobay)

Ciprofloxacin, commonly known as Cipro, is an antibiotic belonging to the quinolone group. It is widely used to treat various kinds of bacterial infections affecting the skin, the abdomen, the lower respiratory tract and the urinary tract. It is commonly prescribed for the treatment of infectious diarrhea, typhoid fever, gonorrhea and prostate infections. Its antibacterial action can be advantageous in cystitis, tuberculosis and ear infections. Cipro is also one of the very few medications proved to treat inhalation anthrax. Crohn’s disease and pneumonia are also treated by this antibiotic. The way it works is that it blocks the enzymes which allow bacteria to reproduce, eventually leading to death of the bacteria. Cipro is a very safe medication with few side effects. The most common of them are dizziness, hallucinations and stomach irritation. An important thing to remember is that Cipro should not be taken with dairy products alone.

J Pharm Biomed Anal. 2005 May 12;
Investigation of the retention/pH profile of zwitterionic fluoroquinolones in reversed-phase and ion-interaction high performance liquid chromatography.
Pistos C, Tsantili-Kakoulidou A, Koupparis M.
Division of Pharmaceutical Chemistry, Department of Pharmacy, University of Athens, Panepistimiopolis, Zografou 15771, Greece.

The retention/pH profiles of three fluoroquinolones, ofloxacin, norfloxacin and ciprofloxacin, was investigated by means of reversed-phase high performance liquid chromatography (RP-HPLC) and reversed-phase ion-interaction chromatography (RP-IIC), using an octadecylsilane stationary phase and acetonitrile as organic modifier. Sodium hexanesulphonate and tetrabutylammonium hydroxide were used as sources of counter ions in ion-interaction chromatography. The retention/pH profiles under in RP-HPLC were compared to the corresponding lipophilicity/pH profiles. Despite the rather hydrophilic nature of the three fluoroquinolones positive retention factors were obtained while there was a shift of the retention maximum towards more acidic pH values. This behavior was attributed mainly to non-hydrophobic silanophilic interactions with the silanized silica gel material of the stationary phase. In ion-interaction chromatography the effect of counter ions over a broad pH range was found to be ruled rather by the ion pair formation in the mobile phase which led to a drastic decrease in retention as a consequence of the disruption of the zwitterionic structure and thereupon the deliberation of a net charge in the molecules. At pH values at which zwitterionic structure was not favored both the ion-exchange and ion pair formation mechanisms were assumed to contribute to the retention.

J Infect Chemother. 2005 Feb;11(1):52-4. Related Articles, Links
Clinical effect of intravenous ciprofloxacin on hospital-acquired pneumonia.
Okimoto N, Yamato K, Honda Y, Kurihara T, Osaki K, Asaoka N, Fujita K, Ohba H.
Division of Respiratory Diseases, Department of Medicine, Kawasaki Medical School Kawasaki Hospital, 2-1-80 Nakasange, Okayama, 700-0821, Japan, kh-info@po.rweb.ne.jp.

The effect of intravenous ciprofloxacin (CPFX) on hospital-acquired pneumonia was examined. The subjects were 32 patients with hospital-acquired pneumonia classified as being in group I, group II, and group III, based on The Japanese Respiratory Society Guidelines for management of hospital-acquired pneumonia. None of the patients had received antibiotic treatment for the pneumonia. CPFX 300 mg was intravenously infused twice daily for 3-14 days, and its clinical effect, bacterological effect, and side effects were examined. Intravenous CPEX was clinically effective in 21 of the 32 patients, with an efficacy rate of 65.6%. With regard to bacteriological efficacy, 4 of 5 strains of methicillin-sensitive Staphylococcus aureus, 2 of 3 strains of Klebsiella pneumoniae, 1 of 2 strains of Streptococcus pneumoniae, 1 of 2 strains of Streptococcus agalactiae, 1 of 2 strains of Pseudomonas aeruginosa, 1 of 2 strains of Serratia marcescens, and the 1 strain of Klebsiella oxytoca were eradicated, with an eradication rate of 42.3% (11 of 26 strains whose fate was confirmed eradicated). Abnormal laboratory findings (side effects) were observed in 11 of the 32 patients (34.4%), but all side effects were mild. Based on the above data, intravenous CPFX may be the drug which should be recommended as the first choice for hospital-acquired pneumonia.

J Antimicrob Chemother. 2005 Feb 24; [Epub ahead of print] Related Articles, Links
Comparative activity of quinolones (ciprofloxacin, levofloxacin, moxifloxacin and garenoxacin) against extracellular and intracellular infection by Listeria monocytogenes and Staphylococcus aureus in J774 macrophages.
Seral C, Barcia-Macay M, Mingeot-Leclercq MP, Tulkens PM, Van Bambeke F.
Unite de pharmacologie cellulaire et moleculaire, Universite catholique de Louvain, Brussels, Belgium.

OBJECTIVES: Quinolones accumulate in eukaryotic cells and show activity against a large array of intracellular organisms, but systematic studies aimed at examining their pharmacodynamic profile against intracellular bacteria are scarce. The present work aims at comparing intracellular-to-extracellular activities in this context. METHODS: We assessed the activities of ciprofloxacin, levofloxacin, moxifloxacin and garenoxacin against the extracellular (broth) and intracellular (infected J774 macrophages) forms of Listeria monocytogenes (cytosolic infection) and Staphylococcus aureus (phagolysosomal infection) using a range of clinically meaningful extracellular concentrations (0.06-4 mg/L). RESULTS: All four quinolones displayed concentration-dependent bactericidal activity against extracellular and intracellular L. monocytogenes and S. aureus for extracellular concentrations in the range 1-4-fold their MIC. Compared at equipotent extracellular concentrations, intracellular activities against L. monocytogenes were roughly equal to those that were extracellular, but were 50-100 times lower against S. aureus. Because quinolones accumulate in cells (ciprofloxacin, approximately 3 times; levofloxacin, approximately 5 times; garenoxacin, approximately 10 times, moxifloxacin, approximately 13 times), these data show that, intracellularly, quinolones are 5-10 times less potent against L. monocytogenes (P=0.065 [ANCOVA]), and at least 100 times less potent (P < 0.0001) against S. aureus. Because of their lower MICs and higher accumulation levels, garenoxacin and moxifloxacin were, however, more active than ciprofloxacin and levofloxacin when compared at similar extracellular concentrations. CONCLUSIONS: Quinolone activity is reduced intracellulary. This suggests that either only a fraction of cell-associated quinolones exert an antibacterial effect, or that intracellular activity is defeated by the local environment, or that intracellular bacteria only poorly respond to the action of quinolones.

J Antimicrob Chemother. 2005 Feb 24; [Epub ahead of print] Related Articles, Links
Comparison of gatifloxacin, moxifloxacin and ciprofloxacin for treatment of experimental Burkholderia pseudomallei infection.
Steward J, Piercy T, Lever MS, Nelson M, Simpson AJ, Brooks TJ.
Biomedical Sciences, Dstl Porton Down, Salisbury SP4 OJQ, UK.

OBJECTIVES: To compare the efficacy of moxifloxacin, gatifloxacin and ciprofloxacin for the post-exposure prophylaxis and treatment of experimental Burkholderia pseudomallei infection. The presence of persistent infection in treated animals and the rate of relapse following dexamethasone treatment were also investigated. METHODS: BALB/c mice were inoculated subcutaneously with 1.75 x 10(6) cfu of B. pseudomallei strain 576. Gatifloxacin, moxifloxacin and ciprofloxacin (100 mg/kg) were given orally at 12 hourly intervals for 14 days starting at 6 h, 7 days or 12 days post-challenge. Control mice did not receive antibiotic therapy. RESULTS: No regimen gave 100% protection. Prophylaxis was most effective when started 6 h post-challenge, with survival rates at 42 days for ciprofloxacin, gatifloxacin and moxifloxacin being 58%, 75% and 75%, respectively. For treatment started at day 7 post-challenge, survival rates were 17%, 11% and 44%, respectively. When antibiotic treatment was delayed until day 12 post-challenge, survival rates fell to 21%, 17% and 28%, respectively. Following dexamethasone treatment of survivors at 42 days post-challenge, relapses occurred in all treatment groups. CONCLUSIONS: Fluoroquinolones do not provide good post-exposure protection against infection with B. pseudomallei. The newer agents moxifloxacin and gatifloxacin are not significantly better than ciprofloxacin for this purpose.

Res Vet Sci. 2004 Oct;77(2):143-51.
Detection of enrofloxacin and its metabolite ciprofloxacin in equine hair.
Dunnett M, Richardson DW, Lees P.
Department of Veterinary Basic Sciences, Royal Veterinary College, Hawkshead Lane, North Mymms, Hatfield, Hertfordshire AL9 7TA, UK. mjdunnett@rvc.ac.uk
Hair analysis to detect drug administration has not been studied extensively in horses. This study aimed to (a) develop an analytical method for enrofloxacin and its metabolite ciprofloxacin in mane and tail hair, (b) relate measured values to doses, routes of administration, hair colour, and (c) demonstrate long-term detectability. Samples were extracted in trifluoroacetic acid at 70 degrees C. Extracts were cleaned-up by solid-phase extraction and analysed by high-performance liquid chromatography with UV-diode array detection. Analyte recoveries were > 87%. Horses were sampled after therapeutic enrofloxacin administration either orally at 7.5 mg/kg daily for 3-13 days or twice daily for 10-14 days (Group 1, n=7) or intravenously at 5.0 mg/kg daily for 12 and 15 days (Group 2, n=2). Enrofloxacin and ciprofloxacin were detected at concentrations up to 452 and 19 ng/mg, respectively, up to 10 months post-treatment. In vitro, enrofloxacin and ciprofloxacin were extensively bound to melanin (> 96%) and in vivo, their uptake was 40-fold greater in black than white hair. Enrofloxacin and ciprofloxacin concentrations correlated to enrofloxacin dose (r2=0.777 and r2=0.769). Enrofloxacin:ciprofloxacin ratios were 21:1 and 13:1 following intravenous and oral administration, respectively. Longitudinal analyte distributions correlated to treatment-sampling interval.

J Infect Dis. 2004 Sep 15;190(6):1150-7. Epub 2004 Aug 03.
Prolonged diarrhea due to ciprofloxacin-resistant campylobacter infection.
Nelson JM, Smith KE, Vugia DJ, Rabatsky-Ehr T, Segler SD, Kassenborg HD, Zansky SM, Joyce K, Marano N, Hoekstra RM, Angulo FJ.
Centers for Disease Control and Prevention, 1600 Clifton Road, Atlanta, GA 30333, USA.
BACKGROUND: Campylobacter causes >1 million infections annually in the United States. Fluoroquinolones (e.g., ciprofloxacin) are used to treat Campylobacter infections in adults. Although human infections with ciprofloxacin-resistant Campylobacter have become increasingly common, the human health consequences of such infections are not well described. METHODS: A case-control study of persons with sporadic Campylobacter infection was conducted within 7 FoodNet sites during 1998-1999. The E-test system (AB Biodisk) was used to test for antimicrobial susceptibility to ciprofloxacin; ciprofloxacin resistance was defined as a ciprofloxacin minimum inhibitory concentration of > or =4 microg/mL. We conducted a case-comparison study of interviewed persons who had an isolate tested. RESULTS: Of 858 isolates tested, 94 (11%) were ciprofloxacin resistant. Among 290 persons with Campylobacter infection who did not take antidiarrheal medications, persons with ciprofloxacin-resistant infection had a longer mean duration of diarrhea than did persons with ciprofloxacin-susceptible infection (9 vs. 7 days [P=.04]). This difference was even more pronounced among the 63 persons who did not take antidiarrheal medications or antimicrobial agents (12 vs. 6 days [P=.04]). In a multivariable analysis-of-variance model, the persons with ciprofloxacin-resistant infection had a longer mean duration of diarrhea than did the persons with ciprofloxacin-susceptible infection (P=.01); this effect was independent of foreign travel. The association between ciprofloxacin resistance and prolonged diarrhea is consistent across a variety of analytical approaches. CONCLUSIONS: Persons with ciprofloxacin-resistant Campylobacter infection have a longer duration of diarrhea than do persons with ciprofloxacin-susceptible Campylobacter infection. Additional efforts are needed to preserve the efficacy of fluoroquinolones.

Am J Hematol. 2004 Sep;77(1):22-5.
Bronchus-associated lymphoid tissue lymphoma arising in a patient with bronchiectasis and chronic Mycobacterium avium infection.
Gaur S, Trayner E, Aish L, Weinstein R.
Department of Medicine, Caritas St. Elizabeth's Medical Center, Tufts University School of Medicine, Boston, Massachusetts 02135, USA.
We describe a 67-year-old woman with bronchiectasis and Mycobacterium avium complex infection who underwent wedge resection of her pulmonary infiltrates because they were progressing despite antibiotic therapy. In addition to the expected granulomatous changes, she was found to have a B-cell lymphoma of bronchus associated lymphoid tissue (BALT). Despite normal bone marrow morphology, marrow involvement was demonstrated by flow cytometry. Her lymphoma remains suppressed with antimycobacterial therapy 6 months after resection of bulk disease. Copyright 2004 Wiley-Liss, Inc.

Br J Surg. 2004 Sep;91(9):1192-6.
Bisphosphonate-ciprofloxacin bound to Skelite is a prototype for enhancing experimental local antibiotic delivery to injured bone.
Buxton TB, Walsh DS, Harvey SB, McPherson JC 3rd, Hartmann JF, Plowman KM.
Department of Clinical Investigation, Dwight David Eisenhower Army Medical Center, Fort Gordon, Georgia 30905, USA. Thomas.Buxton@SE.AMEDD.Army.mil
BACKGROUND: The risk of osteomyelitis after open bone fracture may be reduced by locally applied antibiotics. ENC-41-HP (E41), which comprises ciprofloxacin linked to a 'bone seeking' bisphosphonate, loaded on to carrier Skelite calcium phosphate granules (E41-Skelite) has favourable in vitro characteristics for application to wounded bone. This study assessed E41-Skelite in a rat model of acute tibial osteomyelitis. METHODS: Mechanically induced tibial troughs were contaminated with approximately log10 4 colony forming units (c.f.u.) of Staphylococcus aureus (Cowan 1 strain) 'resistant' to E41 (minimum inhibitory concentration 8-16 microg/ml), lavaged and packed with Skelite alone, or with E41-Skelite slurry. Animals were killed at 24 h (n = 62), 72 h (n = 46) or 14 days (n = 12), and each tibia was assessed for S. aureus load (c.f.u./g tibia) and histological appearance (14 days only). RESULTS: At 24 and 72 h, the tibias of rats treated with E41-Skelite (n = 54) had a significantly lower mean (s.e.m.) load of S. aureus than animals that received Skelite alone (n = 54): log10 3.6(0.2) versus 6.4(0.1) c.f.u./g respectively at 24 h (P < 0.001, Mann-Whitney rank sum test) and log10 4.4(0.2) versus 6.6(0.1) c.f.u./g at 72 h (P < 0.001). At 14 days, E41-Skelite-treated tibias had fewer bacteria, no signs of osteomyelitis and histological signs of healing. CONCLUSION: E41-Skelite, a prototype granulated topical antibiotic delivery system, reduced the development of infection in experimental bone wounds. Copyright 2004 British Journal of Surgery Society Ltd.

Int J Oral Maxillofac Surg. 2004 Sep;33(6):618-20.
Mediastinitis caused by an infected mandibular cyst.
Basa S, Arslan A, Metin M, Sayar A, Sayan MA.
Department of Oral and Maxillofacial Surgery, School of Dentistry, Marmara University, Istanbul, Turkey. ahmetarslan@doctor.com
Descending necrotizing mediastinitis is a potentially fatal condition which may occur seldom as a consequence of oral infections. This report describes the management of a patient with mediastinitis due to an infected dentigerous cyst.

Invest Ophthalmol Vis Sci. 2004 Sep;45(9):3229-33.
Ocular bioerodible minitablets as strategy for the management of microbial keratitis.
Weyenberg W, Vermeire A, Dhondt MM, Adriaens E, Kestelyn P, Remon JP, Ludwig A.
Laboratory of Pharmaceutical Technology and Biopharmacy, University of Antwerp, Antwerp, Belgium.
PURPOSE: Evaluation in volunteers of ciprofloxacin-containing ocular gelling minitablets with prolonged release properties. METHODS: The irritation potential of ciprofloxacin-containing bioadhesive powder mixtures, used to prepare ocular bioerodible minitablets, was evaluated with a slug mucosal-irritation test. The tear pharmacokinetic profiles of ciprofloxacin were determined in six healthy volunteers after topical administration of a minitablet and a single eye drop in the lower fornix. The drug concentrations in the tear samples collected were measured by using a validated HPLC METHOD: Each volunteer was asked to give an evaluation of the preparations applied by answering a standard questionnaire. RESULTS: The results of the mucosal-irritation test demonstrated the nonirritating properties of the bioadhesive powder mixtures. The ocular minitablet, applied in the fornix was in general well tolerated by the healthy volunteers. The mean tear concentration of ciprofloxacin was 33.0, 135.2, and 33.7 microg/g at 30, 300, and 480 minutes after application of the minitablet. Mean tear levels of 84.7, 45.6, and 8.4 microg/g were obtained at 5, 30, and 60 minutes after application of an eye drop. CONCLUSIONS: Due to their prolonged drug release properties, the ocular minitablets containing ciprofloxacin can be considered as a promising drug delivery system to be used in the treatment of ulcerative bacterial keratitis. Copyright Association for Research in Vision and Ophthalmology

Am J Hematol. 2004 Aug;76(4):373-7.
Cardiobacterium hominis endocarditis associated with very severe thrombocytopenia and platelet autoantibodies.
Arnold DM, Smaill F, Warkentin TE, Christjanson L, Walker I.
Department of Hematology, McMaster University, Hamilton, Ontario, Canada.
Severe thrombocytopenia is a life-threatening condition. It is often associated with immune-mediated platelet destruction or myeloablative chemotherapy. Infective endocarditis has been associated with thrombocytopenia, which, as in sepsis, tends to be mild and is often the result of several pathological mechanisms. We report a case of Cardiobacterium hominis endocarditis associated with very severe thrombocytopenia and bleeding in a patient who refused platelet transfusion. Platelet autoantibodies directed against glycoprotein (Gp) IIb/IIIa and Gp Ib/IX were detected during active infection using a glycoprotein-specific assay. Successful treatment of C. hominis endocarditis was associated with loss of platelet autoantibodies and recovery of the platelet count. This report illustrates that the development of platelet autoantibodies can contribute to very severe thrombocytopenia in occasional patients with infective endocarditis. Copyright 2004 Wiley-Liss, Inc.

Am J Ophthalmol. 2004 Aug;138(2):226-30.
A laboratory evaluation of antibiotic therapy for ciprofloxacin-resistant Pseudomonas aeruginosa.
Rhee MK, Kowalski RP, Romanowski EG, Mah FS, Ritterband DC, Gordon YJ.
Charles T. Campbell Laboratory, University of Pittsburgh, Pittsburgh, Pennsylvania, USA. mkrhee@msn.com
PURPOSE: The emergence of ciprofloxacin-resistant Pseudomonas aeruginosa (CRPA) has created a new therapeutic challenge in ophthalmology. We evaluated ophthalmic antibiotics in vitro and in a rabbit keratitis model to determine effective therapy. DESIGN: Experimental laboratory investigation. METHODS: The susceptibilities of 12 CRPA isolates were determined in vitro for amikacin, ceftazidime, tobramycin, polymyxin B, gentamicin, ticarcillin, and the fluoroquinolones (that is, ciprofloxacin, ofloxacin, levofloxacin, gatifloxacin, and moxifloxacin) using E-tests and National Committee of Clinical Laboratory Standards. A rabbit keratitis model was used to determine the reduction in colony counts of CRPA and ciprofloxacin-susceptible P. aeruginosa (CSPA) isolates following topical treatment with polymyxin B/trimethoprim, tobramycin (14 mg/ml), ceftazidime (50 mg/ml), and ciprofloxacin (3 mg/ml). RESULTS: For 12 CRPA isolates, the susceptibilities and median minimum inhibitory concentrations ([MIC]microg/ml) were as follows: amikacin (92%, 14.0), ceftazidime (75%, 4.0), tobramycin (67%, 1.75), polymyxin B (42%, 7.0), gentamicin (17%, 7.0), ticarcillin (0%, >32.0), and all fluoroquinolones (0%, >32.0). While no antibiotic regimen reduced colony counts in the time frame of the animal model for CRPA, ciprofloxacin alone demonstrated a significant decrease in colony counts for CSPA. Comparing CRPA with CSPA, both tobramycin and ciprofloxacin demonstrated a significant decrease in colony counts for CSPA. CONCLUSION: Our laboratory studies suggest that current antibiotics may be suboptimal in treating CRPA keratitis. Until new antibiotics are available, combination therapy such as fortified tobramycin and ticarcillin, and others may prove effective in aggressive topical long-term therapy.

Antimicrob Agents Chemother. 2004 Aug;48(8):3175-8.
Rv2686c-Rv2687c-Rv2688c, an ABC fluoroquinolone efflux pump in Mycobacterium tuberculosis.
Pasca MR, Guglierame P, Arcesi F, Bellinzoni M, De Rossi E, Riccardi G.
Department of Genetics and Microbiology, University of Pavia, 27100 Pavia, Italy.
The Mycobacterium tuberculosis Rv2686c-Rv2687c-Rv2688c operon, encoding an ABC transporter, conferred resistance to ciprofloxacin and, to a lesser extent, norfloxacin, moxifloxacin, and sparfloxacin to Mycobacterium smegmatis. The resistance level decreased in the presence of the efflux pump inhibitors reserpine, carbonyl cyanide m-chlorophenylhydrazone, and verapamil. Energy-dependent efflux of ciprofloxacin from M. smegmatis cells containing the Rv2686c-Rv2687c-Rv2688c operon was observed.

Antimicrob Agents Chemother. 2004 Aug;48(8):3024-7.
Activities of different fluoroquinolones against Bacillus anthracis mutants selected in vitro and harboring topoisomerase mutations.
Grohs P, Podglajen I, Gutmann L.
Service de Microbiologie, Hopital Europeen Georges Pompidou, Paris, France.
Three sets of mutants of Bacillus anthracis resistant to fluoroquinolones were selected on ciprofloxacin and moxifloxacin in a stepwise manner from a nalidixic acid-resistant but fluoroquinolone-susceptible plasmidless strain harboring a Ser85Leu GyrA mutation. A high level of resistance to fluoroquinolones could be obtained in four or five selection steps. In each case, ParC was the secondary target. However, in addition to the GyrA mutation, expression of high-level resistance required (i) in the first set of mutants, active drug efflux associated with a mutation in the QRDR of ParC; (ii) in the second set, two mutations in the QRDR of ParC associated with a mutation in GyrB; and (iii) in the third set, two QRDR mutations, one in ParC and one in GyrA. Interestingly, several selection steps occurred without obvious mutations in the QRDR of any topoisomerase, thereby implying the existence of other resistance mechanisms. Among the fluoroquinolones tested, garenoxacin showed the best activity.

Antimicrob Agents Chemother. 2004 Aug;48(8):2918-23.
Therapeutic efficacy of "nubiotics" against burn wound infection by Pseudomonas aeruginosa.
Dale RM, Schnell G, Wong JP.
Oligos Etc., Inc., Wilsonville, Oregon, USA.
"Nubiotics" are a novel class of proprietary protonated nucleic acid-based drugs shown to have potent in vitro antibacterial activities against a number of gram-positive and gram-negative bacteria. These nubiotics are evaluated here for their in vivo therapeutic efficacy for the treatment of burn wound infection caused by Pseudomonas aeruginosa. To achieve this, a burn wound infection model was established in mice by using a highly pathogenic burn wound clinical isolate of P. aeruginosa. Lethal doses of the bacteria were determined for two routes of infection (subcutaneous and topical), representing systemic and local forms of infection, respectively. Using this infection model, treatment with nubiotics by various routes of drug administration was evaluated and optimized. A total of 12 nubiotics and their analogues were tested and of these, Nu-2, -3, -4, and -5 were found to be extremely efficacious in the postexposure treatment of burn wound infection (60 to 100% survival rates versus 0% for untreated control [P < 0.05]). These nubiotics were effective when given either systemically by intravenous and/or subcutaneous administration or given locally to the affected site in the skin by topical application. Treatment by these two routes resulted in almost 100% survival rates and complete eradication of the bacteria from infection sites in the livers, spleens, and blood. These nubiotics were found to be as effective as intravenously administered ciprofloxacin, a potent and broad-spectrum fluoroquinolone. These results suggest that nubiotics may be a promising and effective approach for the treatment of burn wound infection caused by P. aeruginosa.

Antimicrob Agents Chemother. 2004 Aug;48(8):2793-8.
Comparative effects of ciprofloxacin and ceftazidime on cytokine production in patients with severe sepsis caused by gram-negative bacteria.
Gogos CA, Skoutelis A, Lekkou A, Drosou E, Starakis I, Marangos MN, Bassaris HP.
Department of Internal Medicine, Infectious Diseases Section, Patras University Medical School, Patras, Greece. cgogos@med.upatras.gr
In the present study the effect of ciprofloxacin versus ceftazidime on concentrations of pro- and anti-inflammatory cytokines in the sera of patients with severe sepsis was evaluated. The study included 58 previously healthy patients suffering from severe sepsis caused by gram-negative bacteria, treated with either ciprofloxacin or ceftazidime after thorough clinical and microbiological evaluation and followed up for clinical outcome. Levels of the proinflammatory cytokines tumor necrosis factor alpha (TNF-alpha), interleukin-1b (IL-1b), IL-6, and IL-8 and of the anti-inflammatory cytokine IL-10, as well as of IL-1 receptor antagonist and soluble TNF receptors I and II, in serum were measured at baseline and 24 and 48 h after the first antimicrobial dose. Mean SAPS-II scores, development of septic shock, and mortality rates were similar in the two groups (43.2 +/- 9.2, 21.4%, and 14.3% in the ceftazidime group versus 49.8 +/- 11. 3, 20%, and 13.3% in the ciprofloxacin group). Serum TNF-alpha and IL-6 levels at 24 and 48 h were significantly lower in the ciprofloxacin group, while the IL-10/TNF-alpha ratio was significantly higher, than those for the ceftazidime group. Among patients with high baseline TNF-alpha levels, there were significant increases in the IL-10/TNF-alpha ratio at both 24 and 48 h over that at admission for the ciprofloxacin group, while no differences were noted in the ceftazidime group. These results indicate that ciprofloxacin may have an immunomodulatory effect on septic patients by attenuating the proinflammatory response, while there is no evidence that differences in the cytokines measured have any impact on the final outcome.

Arch Ophthalmol. 2004 Aug;122(8):1166-9.
Comparative efficacy of topical gatifloxacin with ciprofloxacin, amikacin, and clarithromycin in the treatment of experimental Mycobacterium chelonae keratitis.
Hyon JY, Joo MJ, Hose S, Sinha D, Dick JD, O'Brien TP.
Ocular Microbiology and Immunology Laboratory, Wilmer Eye Institute, The Johns Hopkins University School of Medicine, Baltimore, MD 21287-9121, USA.
OBJECTIVE: To determine the comparative efficacy of topical gatifloxacin with ciprofloxacin, fortified amikacin, and clarithromycin against Mycobacterium chelonae keratitis in an animal model. METHODS: Experimental M chelonae keratitis was induced via intrastromal inoculation in a rabbit model. Thirty-five rabbits were randomly divided into 5 groups and each group was treated hourly for 12 hours with topical 0.9% balanced salt solution, 0.3% gatifloxacin, 0.3% ciprofloxacin hydrochloride, a combination of topical fortified amikacin sulfate (50 mg/mL) and clarithromycin (10 mg/mL), or a triple combination of topical 0.3% gatifloxacin, fortified amikacin sulfate (50 mg/mL), and clarithromycin (10 mg/mL). Antibacterial efficacy of each regimen was determined by quantitative bacteriologic analysis. RESULTS: Treatment with 0.3% gatifloxacin or the triple combination of 0.3% gatifloxacin, topical fortified amikacin sulfate (50 mg/mL), and clarithromycin (10 mg/mL) reduced the number of mycobacterial organisms more significantly than the controls that were treated with a topical balanced salt solution (both P<.001). Therapy with 0.3% gatifloxacin was more effective than 0.3% ciprofloxacin alone (P<.001) and demonstrated synergy by enhancing the efficacy of the combination of fortified amikacin (50 mg/mL) and clarithromycin (10 mg/mL) (P<.001). Neither 0.3% ciprofloxacin nor the combination of fortified amikacin (50 mg/mL) and clarithromycin (10 mg/mL) demonstrated a significant difference in activity against mycobacteria compared with the topical balanced salt solution. CONCLUSION: These results suggest that topical 0.3% gatifloxacin ophthalmic solution can be a new initial treatment agent against M chelonae keratitis.Clinical Relevance Topical gatifloxacin 0.3% may provide an initial alternative in therapy of M chelonae keratitis.

Clin Experiment Ophthalmol. 2004 Aug;32(4):424-8.
Trimethoprim-sulphamethoxazole therapy in Nocardia keratitis.
Kalavathy CM, Parmar P, Ramalingam K, Kaliamurthy J, Jesudasan CA, Thomas PA.
Institute of Ophthalmology, Joseph Eye Hospital, Tiruchirappalli, India. cmkala@eth.net
PURPOSE: To describe the clinical features, microbiological features and treatment outcome of nine patients with Nocardia keratitis treated with topical trimethoprim- sulphamethoxazole drops. METHODS: Retrospective review of nine patients with culture-proven Nocardia keratitis. RESULTS: Nine patients with Nocardia keratitis were treated with topical trimethoprim-sulphamethoxazole drops. The average duration of treatment was 25 +/- 9 days. Five of the nine patients presented with superficial ulcers with margins studded with yellowish white discrete pinhead sized infiltration; the other four patients had deep stromal infiltration. Complete healing of the ulcer was achieved in six out of the nine patients with topical trimethoprim- sulphamethoxazole alone or in combination with ciprofloxacin 0.3% eye drops. CONCLUSION: Topical application of trimethoprim-sulphamethoxazole appears to be effective therapy for superficial keratitis due to Nocardia.

Clin Infect Dis. 2004 Aug 1;39(3):303-8. Epub 2004 Jul 08.
US Food and Drug Administration approval of ciprofloxacin hydrochloride for management of postexposure inhalational anthrax.
Meyerhoff A, Albrecht R, Meyer JM, Dionne P, Higgins K, Murphy D.
US Food and Drug Administration, Rockville, MD, USA. am282@gunet.georgetown.edu
In August 2000, the US Food and Drug Administration (FDA) approved ciprofloxacin hydrochloride (Cipro; Bayer) for management of postexposure inhalational anthrax. This was the first antimicrobial drug approved by the FDA for use in treating an infection due to a biological agent used intentionally. The terrorist attacks of 2001 involving anthrax underscore the imperative that safe and effective drugs to manage such infections be readily available in the United States. The approval of ciprofloxacin hydrochloride, which was made on the basis of a surrogate human marker of efficacy, made extensive use of data from an animal model of disease. This represents a new direction in the development of efficacy data in support of drug approval and facilitates the availability of those drugs for which there is an urgent need. This article presents the scientific data and regulatory mechanism that supported the approval of ciprofloxacin hydrochloride for management of postexposure of inhalational anthrax.

J Antimicrob Chemother. 2004 Aug;54(2):451-5. Epub 2004 Jul 01.
Epidemiological characteristics and molecular basis of fluoroquinolone-resistant Neisseria gonorrhoeae strains isolated in Korea and nearby countries.
Yong D, Kim TS, Choi JR, Yum JH, Lee K, Chong Y, Oh HB, Shultz T, Tapsall JW.
Department of Laboratory Medicine, Research Institute of Bacterial Resistance and Brain Korea 21 Project for Medical Sciences, Yonsei University College of Medicine, Seoul, Korea.
OBJECTIVES: This study was performed to examine the cause of the increase in quinolone-resistant Neisseria gonorrhoeae (QRNG) observed in Korea. METHODS: The antimicrobial susceptibilities of 190 isolates of gonococci from Korea in 2000 were examined by NCCLS methods, and subsets of these isolates underwent mutation analysis of the quinolone resistance-determining regions (QRDRs) of gyrA and parC. Molecular epidemiological characterization of 25 Korean isolates and 54 isolates from overseas was performed by pulsed-field gel electrophoresis (PFGE) and the results compared. RESULTS: Most (172, 90.5%) of the 190 gonococci tested displayed reduced susceptibility to ciprofloxacin. All strains with high-level ciprofloxacin resistance (ciprofloxacin MIC >/= 4 mg/L) contained a double amino acid alteration at the 91 and 95 positions in the QRDR of GyrA and a single alteration in ParC. PFGE types of high-level QRNG in Korea were mostly different from those of other nearby countries. CONCLUSIONS: These results suggest that the observed increase in ciprofloxacin-resistant isolates is due to the mutation and spread of Korean multiclonal isolates rather than importation from overseas.

J Antimicrob Chemother. 2004 Aug;54(2):341-7. Epub 2004 Jun 16.
Expression of the efflux pump genes cmeB, cmeF and the porin gene porA in multiple-antibiotic-resistant Campylobacter jejuni.
Pumbwe L, Randall LP, Woodward MJ, Piddock LJ.
Antimicrobial Agents Research Group, Division of Immunity and Infection, University of Birmingham, Birmingham B15 2TT, UK.
AIMS: In Escherichia coli, increased expression of efflux pumps and/or decreased expression of porins can confer multiple antibiotic resistance (MAR), causing resistance to at least three unrelated classes of antibiotics, detergents and dyes. It was hypothesized that in Campylobacter jejuni, the efflux systems CmeABC, CmeDEF and the major outer membrane porin protein, MOMP (encoded by porA) could confer MAR. METHODS: The expression of cmeB, cmeF and porA in 32 MAR C. jejuni isolated from humans or poultry was determined by comparative (C)-reverse transcriptase (RT)-PCR and denaturing DHPLC. A further 13 ethidium bromide-resistant isolates and three control strains were also investigated. Accumulation of ciprofloxacin+/-carbonyl cyanide-m-chlorophenyl hydrazone (CCCP) was also determined for all strains. RESULTS: Although resistance to ethidium bromide has been associated with MAR, expression of all three genes was similar in the ethidium bromide-resistant isolates. These data indicate that CmeB, CmeF and MOMP play no role in resistance to this agent in C. jejuni. Six MAR isolates over-expressed cmeB, 3/32 over-expressed cmeB and cmeF. No isolates over-expressed cmeF alone. Expression of porA was similar in all isolates. All nine isolates that over-expressed cmeB contained a mutation in cmeR, substituting glycine 86 with alanine. All cmeB over-expressing isolates also accumulated low concentrations of ciprofloxacin, which were restored to wild-type levels in the presence of CCCP. CONCLUSIONS: These data indicate that over-expression of cmeB is associated with MAR in isolates of C. jejuni. However, as cmeB was over-expressed by only one-third (9/32) of MAR isolates, these data also indicate other mechanisms of MAR in C. jejuni.

J Clin Pharm Ther. 2004 Aug;29(4):381-7.
Determination of ciprofloxacin concentrations in human serum and urine by HPLC with ultraviolet and fluorescence detection.
Sowinski KM, Kays MB.
Department of Pharmacy Practice, School of Pharmacy and Pharmacal Sciences, Purdue University, Indianapolis, IN, USA. ksowinsk@iupui.edu
OBJECTIVE: To develop a simple and sensitive high performance liquid chromatography method for the determination of ciprofloxacin concentrations in human serum and urine. METHOD: Serum proteins were removed by ultrafiltration through a filtering device after the addition of a displacing reagent. Urine samples were diluted with mobile phase prior to injection. Separation was achieved with a C18 reverse-phase column and using ultraviolet (UVD) and fluorescence detection (FD) for serum samples and UVD for urine samples. RESULTS: The quantitation limits of the assay were 20 ng/ml (FD) and 100 ng/ml (UVD) in serum and 1 microg/ml in urine. The assay was successfully applied to a pharmacokinetic study of ciprofloxacin in healthy volunteers. CONCLUSION: The method presented for ciprofloxacin assay in human serum and urine requires less sample clean up and is more sensitive than those reported in the literature.

Res Vet Sci. 2004 Aug;77(1):67-71.
In vitro antimicrobial activity of orbifloxacin against Staphylococcus intermedius isolates from canine skin and ear infections.
Ganiere JP, Medaille C, Etore F.
Unite de Pathologie Infectieuse, Ecole Nationale Veterinaire, Route de Gachet, BP 40706, 44307 Nantes 03, France. ganiere@vet-nantes.fr
The objective of the study was to evaluate the in vitro activity of orbifloxacin against Staphylococcus intermedius strains isolated in France from canine skin and ear infections. The minimum inhibitory concentrations (MICs) of orbifloxacin against 240 field S. intermedius isolates (69 skin and 171 ear isolates) ranged from 0.016 to 8 mg l(-1), with MIC50 and MIC90 equal to 0.5 and 1 mg l(-1), respectively. Only one strain, a pyoderma isolate was resistant (MIC=8 mg l(-1)). Orbifloxacin was tested at different concentrations for killing rate against five isolates obtained from pyoderma cases and against a reference strain (Staphylococcus aureus ATCC 29213). Orbifloxacin expressed a concentration-dependent bactericidal activity against the S. aureus reference strain, but a time-dependent bactericidal activity against S. intermedius. Orbifloxacin induced bactericidal effect against the S. intermedius strains tested with concentrations equal to or two times MIC.

Biochem Pharmacol. 2004 Jul 15;68(2):395-402.
Role of CYP1A2 and CYP2E1 in the pentoxifylline ciprofloxacin drug interaction.
Peterson TC, Peterson MR, Wornell PA, Blanchard MG, Gonzalez FJ.
Department of Medicine, Faculty of Medicine, Dalhousie University, Halifax, NS, Canada. tcpmed@dal.ca
In this study the drug interaction between ciprofloxacin (CIPRO) and pentoxifylline (PTX) was investigated and the role of CYP1A2 in the drug interaction was determined with the aid of a selective CYP1A2 inhibitor, furafylline (FURA), and the Cyp1A2 knockout mouse. Serum concentrations of PTX (83.4+/-1 micromol/l) and metabolite-1 (M-1) (13.7+/-2.8 micromol/l) following a single injection of PTX (100 mg/kg i.p.) were significantly higher (P<0.05) in mice treated with CIPRO (25 mg/kg i.p. 9 days) compared to serum concentrations of PTX (46.3+/-0.5 micromol/l) and M-1 (6.4+/-1.1 micromol/l) in mice administered saline. Murine hepatic microsomes were incubated with PTX alone or the combination of PTX and CIPRO. The metabolism of PTX in the murine hepatic microsomes containing both CIPRO and PTX was significantly decreased compared to microsomes incubated with PTX alone, suggesting that CIPRO may inhibit the metabolism of PTX. To further clarify the role of CYP1A2 in the metabolism of PTX in mice, the effect of a selective CYP1A2 mechanism based inhibitor, FURA, on the metabolism of PTX was investigated and our results indicate that FURA inhibited metabolism of PTX. We then investigated PTX elimination in the Cyp1A2 knockout mouse. Blood levels of PTX were assessed at 2 and 20 min following a single injection of PTX (32 mg/kg i.v). Serum concentration of PTX was determined in Cyp1A2 knockout mice compared to Cyp1A2 wild type control mice. The serum concentration of PTX in Cyp1A2 wild type mice (n=9) was 22.2+/-3.2 micromol/l at 20 min following injection of PTX. The serum concentration of PTX in Cyp1A2 knockout mice (n=11) was significantly elevated at 20 min following injection of PTX compared to Cyp1A2 wild type mice. These results clearly indicate that inhibition of CYP1A2 catalytic activity that occurs in the Cyp1A2 knockout mice is sufficient to alter metabolism of PTX and result in markedly elevated levels in serum of Cyp1A2 knockout mice. The results of Western analysis in murine microsomes suggest that CYP1A2 protein levels were not altered by CIPRO indicating that CIPRO did not downregulate Cyp1A2. The results of Western analysis also indicated that CIPRO treatment increased CYP2E1 in mouse microsomes and the implications of these will be discussed.

Lakartidningen. 2004 Jul 8;101(28-29):2332-5.
Increasing incidence of ciprofloxacin resistant gonorrhea in Sweden. Choose a correct antibiotic and follow up the treatment!
Berglund T, Colucci B, Lund B, Qvarnstrom I, Sandstrom E.
Avdelningen for epidemiologi, Smittskyddsinstitutet, Solna, Sweden. torsten.berglund@smi.ki.se
The incidence of gonorrhoea has increased in Sweden and is now three times higher than in the middle of the 1990's. A remarkable increase of ciprofloxacin resistant gonorrhoea has been reported in Stockholm and other parts of Sweden during 2003. Among men attending a clinic for homosexual men in Stockholm the ciprofloxacin resistant cases have increased from a low level to over 50% during the last year. Most of the homosexual men are exposed in Stockholm and one serotype is dominant. Also in the county of Gävleborg there has been an outbreak of ciprofloxacin resistant gonorrhoea among young heterosexual men and women. No resistance to cefixime, ceftriaxone and spectinomycin has been noted and these antibiotics are then a better first choice of treatment in a Swedish context.

J Am Acad Dermatol. 2003 Nov;49(5 Suppl):S267-9.
Stevens-Johnson syndrome associated with ciprofloxacin: a review of adverse cutaneous events reported in Sweden as associated with this drug.
Hallgren J, Tengvall-Linder M, Persson M, Wahlgren CF.
Department of Dermatology, Karolinska Hospital, Karolinska Institute, Stockholm, Sweden.
Stevens-Johnson syndrome is a severe mucocutaneous reaction, which can be elicited by various drugs. We present 2 cases with this syndrome associated with ciprofloxacin treatment and review the adverse cutaneous events reported as possibly related to ciprofloxacin treatment in Sweden between 1988 and 2000. Eight cases, excluding ours, of Stevens-Johnson syndrome, toxic epidermal necrolysis, and erythema multiforme were reported. This implies an annual incidence of these adverse cutaneous events of 0.045 per 100,000 treated patients (assuming an average treatment length of 10 days). One patient died, but ciprofloxacin was not considered to be the major cause of death. Together with previous data from the literature, our report supports the view that ciprofloxacin can cause severe adverse cutaneous events.

Antimicrob Agents Chemother. 2003 Dec;47(12):3789-94.
Wagenlehner FM, Wydra S, Onda H, Kinzig-Schippers M, Sorgel F, Naber KG.
Department of Urology, St. Elisabeth Hospital, Straubing. Institute for Biomedical and Pharmaceutical Research (IBMP), Nurnberg-Heroldsberg, Germany.
Concentrations in Plasma, Urinary Excretion, and Bactericidal Activity of Linezolid (600 Milligrams) versus Those of Ciprofloxacin (500 Milligrams) in Healthy Volunteers Receiving a Single Oral Dose.
In a randomized crossover study, 12 volunteers (6 males, 6 females) received a single oral dose of 600 mg of linezolid or 500 mg of ciprofloxacin to assess the concentrations in plasma (up to 24 h), urinary excretion (by high-pressure liquid chromatography), and bactericidal titers in urine (UBT) at intervals up to 120 h. The mean maximum concentration of linezolid in plasma was 13.1 mg/liter, and that of ciprofloxacin was 2.46 mg/liter. The median cumulative levels of renal excretion of the administered dose of the parent drug were 44% for linezolid (range, 28 to 47%; mean +/- standard deviation, 40% +/- 7.8%) and 43% for ciprofloxacin (range, 20 to 56%; mean +/- standard deviation, 40% +/- 9.3%). The UBTs, i.e., the highest twofold dilution (with antibiotic-free urine used as the diluent) of urine that was still bactericidal, were determined for a reference strain and five gram-positive clinical uropathogens for which the MICs of linezolid and ciprofloxacin were as follows: Staphylococcus aureus ATCC 27278, 2 and 0.25 mg/liter, respectively; Staphylococcus aureus (methicillin susceptible), 1 and 16 mg/liter, respectively; Staphylococcus aureus (methicillin resistant), 2 and 64 mg/liter, respectively; Staphylococcus saprophyticus (methicillin susceptible), 1 and 0.25 mg/liter, respectively; Enterococcus faecalis, 2 and 1 mg/liter, respectively; and Enterococcus faecium, 2 and 1 mg/liter, respectively. The median UBTs of linezolid measured within the first 6 h were 1:96 for each of the two enterococcal strains and between 1:128 and 1:256 for the four staphylococcal strains. The median UBTs of ciprofloxacin were 1:64 for the two enterococcal strains; between 1:384 and 1:512 for the two ciprofloxacin-susceptible strains; and 1 (bactericidal activity of undiluted urine only) and 1:2 for the two resistant staphylococcal strains, respectively. The areas under the UBT-time curve (AUBT) for linezolid and ciprofloxacin showed no statistically significant (P < 0.05) differences except for a better AUBT for linezolid for the two ciprofloxacin-resistant staphylococcal strains. For linezolid there were no statistically significant differences in UBTs or AUBTs for ciprofloxacin-susceptible and -resistant strains. Thus, the bactericidal activities of linezolid and ciprofloxacin against susceptible strains in urine were comparable, whereas linezolid also exhibited the same good bactericidal activity against ciprofloxacin-resistant strains. Therefore, linezolid should be tested for use as empirical treatment for complicated urinary tract infections due to gram-positive uropathogens in an appropriate clinical trial.

J Antimicrob Chemother. 2003 Oct 29
Livermore DM, Nichols T, Lamagni TL, Potz N, Reynolds R, Duckworth G.
Antibiotic Resistance Monitoring & Reference Laboratory, Specialist & Reference Microbiology Division.
Ciprofloxacin-resistant Escherichia coli from bacteraemias in England; increasingly prevalent and mostly from men.
OBJECTIVES: To assess ciprofloxacin resistance among Escherichia coli isolates from bacteraemia patients in England in relation to age, sex and Region. METHODS: Routine susceptibility data for bacteraemia isolates were collected from over 90% of hospitals in England. RESULTS: During 1995-2001, the prevalence of ciprofloxacin resistance trebled, from 2.1% to 6.5%. Isolates from men were more frequently resistant than those from women, possibly because infections in men more often involve nosocomial strains. Resistance was rare (<1.5%) in isolates from patients aged <1 year; among older patients, resistance was unrelated to age in isolates from women, but peaked in the 15-44 age group for men. CONCLUSIONS: The prevalence of ciprofloxacin resistance in E. coli from bacteraemia is strongly associated with sex and, to a lesser extent, age.

Jpn J Infect Dis. 2003 Aug;56(4):156-7.
Mandal S, Mandal MD, Pal NK.
Department of Bacteriology and Serology, Calcutta School of Tropical Medicine, Kolkata, India.
Combination effect of ciprofloxacin and gentamicin against clinical isolates of Salmonella enterica serovar typhi with reduced susceptibility to ciprofloxacin.
The present study evaluated the in vitro efficacy of ciprofloxacin (CPFX) in combination with gentamicin (GM) using agar dilution checkerboard method against six blood culture isolates of Salmonella enterica serovar Typhi with CPFX minimum inhibitory concentration (MIC) values of 0.75 - 1.25 microg/ml and GM MIC values of 0.75 - 2 microg/ml. When used in combination, the fractional inhibitory concentration (FIC) values of CPFX and GM for the isolates ranged from 0.008 - 0.032 microg/ml and 0.1 - 0.2 microg/ml, respectively. The range of the FIC index from 0.121 - 0.216 indicated the synergistic effect between CPFX and GM for all the isolates. The time-kill method, which showed a 2.64 log(10) decrease in CFU/ml between the combination and its more active compound, also established synergism between CPFX and GM against one isolate employed in the method. These results may be helpful in making clinical decisions in the treatment of enteric fever due to the infection of multidrug resistant S. enterica serovar Typhi.

Med Dosw Mikrobiol. 1996;48(3-4):169-75.
Kalisz J, Denys A, Szczerba W, Rusinek A, Rogowska-Kalisz A.
Zaklad Mikrobiologii Lekarskiej WAM w Lodzi.
Microbiological evaluation of ciprofloxacin efficacy for treatment of urinary tract infections
An attempt has been undertaken to evaluate the aetiology of urinary tract infections in a large group of patients and to determine the resistance to ciprofloxacin during therapy, and the efficacy of the drug in treating of urinary tract infections. 52 patients with urinary tract infections were treated with ciprofloxacin. Ciprobay by BAYER was used in coated 500 mg tablets twice a day and intravenous solutions in 200 mg dosages every 12 hours for 10-14 days depending on the clinical condition. Microbiological tests were made according to general methods. Sensitivity evaluation to ciprofloxacin was done using E-tests by AB Biodisk and dilution tests. The most common a etiology of urinary tract infections were Gram-negative Enterobacteriaceae rods, mainly E. coli. Ciprofloxacin gave the best results against Enterobacteriaceae rods (100% eradications). In other infections, effective therapy was possible after determining of the sensitivity in vitro. S. haemolyticus bacteria tended significantly towards resistance to ciprofloxacin during therapy.