Ciprofloxacin Monotherapy Research Articles

The Comparative Effectiveness of Ciprofloxacin and Metronidazole for an Initial Episode of Pouchitis: A Propensity-Matched Study.

There is minimal evidence regarding the comparative effectiveness of individual antibiotics in the treatment of pouchitis. We sought to evaluate the comparative effectiveness of ciprofloxacin monotherapy, metronidazole monotherapy, and combination therapy (ciprofloxacin and metronidazole) in the treatment of an initial episode of pouchitis after ileal pouch-anal anastomosis for ulcerative colitis (UC). We performed a retrospective cohort study in TriNetX, a global federated research network of electronic health records. Primary outcomes were failure of initial antibiotic therapy and the development of recurrent pouchitis in the first 12 months after an initial episode of pouchitis. One-to-one propensity score matching was performed for age, sex, race, primary sclerosing cholangitis, nicotine dependence, obesity, and previous exposure to tumor necrosis factor inhibitors between the cohorts. Among 271 patients who developed pouchitis (mean age at ileal pouch-anal anastomosis 35.8 years, male sex 57%) and were treated with ciprofloxacin, metronidazole, or combination therapy, 190 (70%) developed recurrent pouchitis. After propensity score matching, there was no significant difference in the odds of early relapse or nonresponse with ciprofloxacin compared with metronidazole monotherapy (adjusted odds ratio 0.56, 95% confidence interval 0.23-1.34) or when either monotherapy was compared with combination therapy. There was also no significant difference in odds of recurrent pouchitis when comparing patients treated with ciprofloxacin with metronidazole monotherapy (adjusted odds ratio 0.86, 95% confidence interval 0.40-1.84) or either monotherapy with combination therapy. In this retrospective cohort study, we demonstrated no significant difference in the real-world effectiveness of ciprofloxacin, metronidazole, or combination therapy for the initial episode of pouchitis.

Post-traumatic endophthalmitis prophylaxis: a systematic review and meta-analysis

PurposeThe goal of this study is to determine if certain aspects of endophthalmitis prophylaxis strategies are superior to others.DesignThis investigation is a systematic review and meta-analysis.MethodsAll studies specifying a type of prophylaxis strategy and resulting rates of endophthalmitis were included. Time course, method of administration, and antibiotic regimen, and confounding factors were collected and included for meta-regression.ResultsTime courses greater than 24 h did not significantly improve outcomes. Likewise, intraocular and/or intravenous antibiotic administration methods did not significantly outperform oral administration. No antibiotic regimens performed differently from vancomycin/ ≥ 3rd generation cephalosporin except for ciprofloxacin monotherapy which yielded significantly worse outcomes.ConclusionsFuture antibiotic strategies should strongly consider the risks of antibiotic treatment > 24 h and administration methods other than the oral antibiotic forms. In addition, providers should be wary of using ciprofloxacin monotherapy for endophthalmitis prophylaxis when treating open globe injuries.

Pasteurella multocida Endocarditis with Septic Arthritis: Case Report and Review of the Literature

Background: There is a paucity of evidence regarding optimal management of Pasteurella spp. endocarditis. The authors report the first case of Pasteurella spp. endocarditis with septic arthritis and review the literature. Case Description: A 79-year-old patient with significant comorbidities, including prosthetic aortic valve, was admitted with left knee swelling, fever, and confusion, having been scratched by a cat 2-weeks prior. At presentation, there was a metallic click, a Grade 3 pan-systolic murmur and Grade 1 flow murmur audible on auscultation. Blood and synovial fluid cultures both isolated Pasteurella multocida, identified by matrix-assisted laser desorption ionisation–time of flight, which was sensitive to penicillin according to the European Committee on Antimicrobial Susceptibility Testing (EUCAST); minimum inhibitory concentration: 0.094). The patient underwent joint washout and received intravenous piperacillin/tazobactam for 3 days before switching to benzylpenicillin once sensitivities were known. Due to continued pyrexia, a transthoracic echocardiogram was obtained, which revealed a small mobile mass on a thickened mitral valve suspicious for a vegetation. On review by the Infective Endocarditis team, conservative management was deemed best, given the presence of comorbidities. Despite requiring further joint washout due to persistent knee pain, the patient was successfully treated with 8 weeks of antibiotic therapy (24 days of benzylpenicillin monotherapy, 2 weeks of benzylpenicillin and ciprofloxacin, and 15 days ciprofloxacin monotherapy). Discussion: Previous literature reviews report a higher mortality of Pasteurella spp. endocarditis when managed without cardiac surgery, thus recommending surgery in all cases. The authors found these to have confounding factors, including inadequate duration of antimicrobials, aortic root abscess, and rapid progression to death. The authors’ case of Pasteurella spp. endocarditis, complicated by septic arthritis, showed successful therapy without cardiac surgery.

Comparison of a combined regimen of fosfomycin and ciprofloxacin with ciprofloxacin alone as antimicrobial prophylaxis for transrectal prostate biopsy in the era of high fluoroquinolone-resistant rectal flora.

BackgroundTo assess the prophylactic effect of fosfomycin (FM) and ciprofloxacin combinations for infectious complications of transrectal ultrasound-guided prostate biopsy (TRUSPB) compared to that of ciprofloxacin alone.MethodsIn total, 1,578 patients were enrolled and were divided into two groups according to the prophylactic antibiotics. Group 1 (n = 1234) received ciprofloxacin on the day of the biopsy and for an additional 1–2 days, whereas Group 2 (n = 334) was given FM in addition to ciprofloxacin in the same manner as Group 1. The primary outcome was overall infectious complications within 1 month of TRUSPB. The secondary outcome was the risk factors of infectious complications after TRUSPB.ResultsInfectious complications occurred in 31 patients (2.5%) and 1 patient (0.3%) in Groups 1 and 2, respectively. Our results indicated that fluoroquinolone (FQ) and FM significantly reduced the risk of infectious complications compared to FQ (relative risk: 0.12; 95% confidence interval 0.02–0.87, P = 0.015). Based on the multivariate analysis, previous antibiotic exposure (odds ratio [OR] = 3.59, P = 0.026), and the addition of FM (OR = 0.12, P = 0.038) were associated with infectious complications. Based on the rectal swab, FQ resistance was 28.0% (n = 294) in total. FQ resistance in the FQ and FM group was higher than that in the FQ group (n = 178, 54.9% vs. n = 116, 16.0%, P < 0.001).ConclusionThe combination of ciprofloxacin and FM exhibited reduced infectious complications after TRUSPB compared with ciprofloxacin monotherapy and may be applicable in the era of the high abundance of FQ-resistant rectal flora.

Adjunctive S100A8/A9 Immunomodulation Hinders Ciprofloxacin Resistance in Pseudomonas aeruginosa in a Murine Biofilm Wound Model.

Objective Pseudomonas aeruginosa is known to contribute to the pathogenesis of chronic wounds by biofilm-establishment with increased tolerance to host response and antibiotics. The neutrophil-factor S100A8/A9 has a promising adjuvant effect when combined with ciprofloxacin, measured by quantitative bacteriology, and increased anti- and lowered pro-inflammatory proteins. We speculated whether a S100A8/A9 supplement could prevent ciprofloxacin resistance in infected wounds.MethodFull-thickness 2.9cm2-necrosis was inflicted on 32 mice. On day 4, P.aeruginosa in seaweed alginate was injected sub-eschar to mimic a mono-pathogenic biofilm. Mice were randomized to receive ciprofloxacin and S100A8/A9 (n=14), ciprofloxacin (n=12) or saline (n=6). Half of the mice in each group were euthanized day 6 and the remaining day 10 post-infection. Mice were treated until sacrifice. Primary endpoint was the appearance of ciprofloxacin resistant P.aeruginosa. The study was further evaluated by genetic characterization of resistance, means of quantitative bacteriology, wound-size and cytokine-production.ResultsThree mice receiving ciprofloxacin monotherapy developed resistance after 14 days. None of the mice receiving combination therapy changed resistance pattern. Sequencing of fluoroquinolone-resistance determining regions in the ciprofloxacin resistant isolates identified two high-resistant strains mutated in gyrA C248T (MIC>32µg/ml) and a gyr B mutation was found in the sample with low level resistance (MIC=3µg/ml). Bacterial densities in wounds were lower in the dual treated group compared to the placebo group on both termination days.ConclusionThis study supports the ciprofloxacin augmenting effect and indicates a protective effect in terms of hindered ciprofloxacin resistance of adjuvant S100A8/A9 in P.aeruginosa biofilm infected chronic wounds.

An open-label, randomized, non-inferiority trial of the efficacy and safety of ciprofloxacin versus streptomycin + ciprofloxacin in the treatment of bubonic plague (IMASOY): study protocol for a randomized control trial

BackgroundBubonic plague is the primary manifestation of infection with Yersinia pestis, accounting for 90% of all plague cases and with 75% of global cases reported in Madagascar. All drugs in use for treating plague are registered based on experimental data and anecdotal evidence, and no regimen currently recommended is supported by a randomized clinical trial. The IMASOY trial intends to fill this knowledge gap by comparing two 10-day regimens included in the national guidelines in Madagascar. The primary objective of the trial is to test the hypothesis that ciprofloxacin monotherapy is non-inferior to streptomycin followed by ciprofloxacin for the treatment of bubonic plague, thus avoiding the need for injectable, potentially toxic, aminoglycosides.MethodsA two-arm parallel-group randomized control trial will be conducted across peripheral health centres in Madagascar in five districts. Males and non-pregnant females of all ages with suspected bubonic or pneumonic plague will be recruited over the course of three plague ‘seasons’. The primary endpoint of the trial is to assess the proportion of patients with bubonic plague who have a therapeutic response to treatment (defined as alive, resolution of fever, 25% reduction in the size of measurable buboes, has not received an alternative treatment and no clinical decision to continue antibiotics) as assessed on day 11.DiscussionIf successful, the trial has the potential to inform the standard of care guidelines not just in Madagascar but in other countries afflicted by plague. The trial is currently ongoing and expected to complete recruitment in 2022.Trial registrationClinicalTrials.gov NCT04110340. Registered on 1 October 2019

Inhalable liposomal powder formulations for co-delivery of synergistic ciprofloxacin and colistin against multi-drug resistant gram-negative lung infections.

The aim of this study was to design and characterize dry powder inhaler formulations of ciprofloxacin and colistin co-loaded liposomes prepared by the ultrasonic spray-freeze-drying (USFD) technique. Liposomal formulations and powder production parameters were optimized to achieve optimal characteristics and in-vitro performance such as encapsulation efficiency (EE), particle size, particle distribution index (PDI), fine particle fraction (FPF), emitted dose (ED) and in vitro antibacterial activity. The formulation (F6) with the mannitol (5% w/v) as the internal lyoprotectant and sucrose (5%, w/v), mannitol (10%, w/v) and leucine (5%, w/w) as the external lyoprotectants/aerosolization enhancers showed an optimal rehydrated EE values of ciprofloxacin and colistin (44.9±0.9% and 47.0±0.6%, respectively) as well as satisfactory aerosol performance (FPF: 45.8±2.2% and 43.6±1.6%, respectively; ED: 97.0±0.5% and 95.0±0.6%, respectively). For the blank liposomes, there was almost no inhibitory effect on the cell proliferation in human lung epithelial A549 cells, showing that the lipid materials used in the liposome formulation is safe for use in pulmonary drug delivery. The cytotoxicity study demonstrated that the optimized liposomal formulation (F6) was not cytotoxic at least at the drug concentrations of colistin 5μg/mL and ciprofloxacin 20μg/mL. Colistin (2mg/L) monotherapy showed no antibacterial effect against P. aeruginosa H131300444 and H133880624. Ciprofloxacin (8mg/L) monotherapy showed moderate bacterial killing for both clinical isolates; however, regrowth was observed in 6h for P. aeruginosa H133880624. The liposomal formulation displayed superior antibacterial activity against clinical isolates of Pseudomonas aeruginosa H131300444 and P. aeruginosa H133880624 compared to each antibiotic per se. These results demonstrate that the liposomal powder formulation prepared by USFD could potentially be a pulmonary delivery system for antibiotic combination to treat multi-drug resistant Gram-negative lung infections.

Outcomes of Third-Generation Cephalosporin Plus Ciprofloxacin or Doxycycline Therapy in Patients with Vibrio vulnificus Septicemia: A Propensity Score-Matched Analysis.

BackgroundCombination therapy with a third-generation cephalosporin (TGC) and a tetracycline analogue is recommended for Vibrio vulnificus infection. The combination of a TGC and ciprofloxacin has synergistic in vitro bactericidal activity against V. vulnificus. No clinical study has compared the standard regimen with TGC plus ciprofloxacin therapy for V. vulnificus infection.MethodsPatients with a confirmed V. vulnificus infection at two medical centers in Korea from 1991 to 2016 were enrolled in this study. The patients were grouped according to the type of antibiotic administered. A retrospective propensity-score-matched case-control study of patients treated with TGC plus doxycycline or TGC plus ciprofloxacin was performed. The clinical characteristics and outcomes of the patients were analyzed.ResultsA total of 218 patients were confirmed to have V. vulnificus septicemia during the study, and the 30-day survival rate was 39% (85/218). The patients were classified into the following six treatment groups: TGC monotherapy (n = 82), TGC plus doxycycline therapy (n = 42), TGC plus ciprofloxacin therapy (n = 39), ciprofloxacin monotherapy (n = 14), other β-lactam monotherapy (n = 10), and other (n = 31). The survival rates of these groups were as follows: TGC monotherapy (35%), TGC plus doxycycline (38%), TGC plus ciprofloxacin (54%), ciprofloxacin monotherapy (29%), other β-lactam (20%), and other (39%). The 30-day survival rate showed no significant difference between the TGC plus doxycycline and TGC plus ciprofloxacin groups (log-rank test, P = 0.18). Among the 81 patients treated with TGC plus doxycycline or TGC plus ciprofloxacin, 12 per treatment group were selected by propensity-score matching. There was no significant difference in the baseline characteristics or the frequency of fasciotomy between the two groups. The 30-day survival rate showed no significant difference between the TGC plus doxycycline (50%) and TGC plus ciprofloxacin (67%) groups (log-rank test, P = 0.46).ConclusionOur data suggest that the outcome of TGC plus ciprofloxacin therapy was comparable to that of TGC plus doxycycline therapy in patients with V. vulnificus septicemia.

Treatment of Ciprofloxacin-resistant Ear Infections.

Ciprofloxacin resistance has been reported in 4.5% of patients with otorrhea and is increasing in prevalence. Due to ototoxicity, only fluoroquinolones are Food and Drug Administration approved for topical therapy in the middle ear. Furthermore, there is an assumption that antibiotic resistance is less relevant to topical therapy due to in vivo concentrations much higher than the minimum inhibitory concentration used to determine resistance. This study investigates ciprofloxacin-resistant infections and seeks to develop a better understanding of treatment options and outcomes. Retrospective review of 141 ciprofloxacin-resistant otologic infections. Tertiary-care hospital. Patients with culture-proven ciprofloxacin-resistant infections from 2008 to 2017. Antibiotic treatment with ciprofloxacin topical drops, ciprofloxacin plus oral antibiotics, and nonciprofloxacin therapy. Bacteriology for ciprofloxacin-resistant infections and treatment effectiveness of various therapies. Methicillin-resistant Staphylococcus aureus (33%), Corynebacterium striatum (19%), and non-Methicillin-resistant Staphylococcus aureus (11%) are the most frequent causes of ciprofloxacin-resistant infections. Topical ciprofloxacin monotherapy was successful in 2.7% of infections compared with a 64.7% success rate with the addition of an oral antibiotic (p < 0.001). Nonciprofloxacin drops are more effective with a 70% cure rate compared with the 2.7% of the ciprofloxacin drops p < 0.001. There was no difference in treatment efficacy when comparing nonciprofloxacin topical therapy (70% cure) to nonciprofloxacin topical therapy plus oral antibiotic (83% cure, p = 0.17). Using ciprofloxacin drops to treat ciprofloxacin-resistant bacteria is ineffective and patients do significantly better with alternative therapy. This finding supports the conclusion that high concentrations achieved in topical applications are not sufficient to overcome antibiotic resistance.

Synergistic interaction between phage therapy and antibiotics clears Pseudomonas aeruginosa infection in endocarditis and reduces virulence

Background.Increasing antibiotic resistance warrants therapeutic alternatives. Here we investigated the efficacy of bacteriophage-therapy (phage) alone or combined with antibiotics against experimental endocarditis (EE) due to Pseudomonas aeruginosa, an archetype of difficult-to-treat infection.Methods.In vitro fibrin clots and rats with aortic EE were treated with an antipseudomonas phage cocktail alone or combined with ciprofloxacin. Phage pharmacology, therapeutic efficacy, and resistance were determined.Results.In vitro, single-dose phage therapy killed 7 log colony-forming units (CFUs)/g of fibrin clots in 6 hours. Phage-resistant mutants regrew after 24 hours but were prevented by combination with ciprofloxacin (2.5 × minimum inhibitory concentration). In vivo, single-dose phage therapy killed 2.5 log CFUs/g of vegetations in 6 hours (P < .001 vs untreated controls) and was comparable with ciprofloxacin monotherapy. Moreover, phage/ciprofloxacin combinations were highly synergistic, killing >6 log CFUs/g of vegetations in 6 hours and successfully treating 64% (n = 7/11) of rats. Phage-resistant mutants emerged in vitro but not in vivo, most likely because resistant mutations affected bacterial surface determinants important for infectivity (eg, the pilT and galU genes involved in pilus motility and LPS formation).Conclusions.Single-dose phage therapy was active against P. aeruginosa EE and highly synergistic with ciprofloxacin. Phage-resistant mutants had impaired infectivity. Phage-therapy alone or combined with antibiotics merits further clinical consideration.

Influence of Menstrual Cycle on Pharmacokinetics of Ciprofloxacin

The aim of our research work is to study the influence of menstrual cycle on the pharmacokinetic parameters of the Ciprofloxacin in patients with infections . Plasma samples were collected from 12 female patients on long term oral Ciprofloxacin monotherapy (not less than two years) with prescribed dosage regimen dose at the time points of 0, 1, 2, 3, 4, 6, 8 &12 hours after dosing and analysed for drug content by HPLC method. Mean Cmax of Ciprofloxacin was decreased by 20% in the ovulatory phase compared to that of follicular phase. The AUC0-∞ of Ciprofloxacin i.e, bioavailability was decreased in luteal phase by 20% than follicular phase. Volume of distribution of Ciprofloxacin was significantly lower in follicular and luteal phases compared to ovulatory phase. Ciprofloxacin half-life was decreased and clearance was increased in luteal phase compared to follicular phase. Except Vd/f and Vss/f, menstrual cycle phases did not significantly affect the pharmacokinetic profile of Ciprofloxacin in terms of Cmax, Tmax, AUC0-∞, AUMC0-∞, t1/2, MRT, clearance and absorption rate constant. From the above observations it can be concluded that, menstrual hormonal changes influenced Ciprofloxacin pharmacokinetics to a lesser extent and Vd/f and Vss/f were significantly altered. Mean plasma concentrations of Ciprofloxacin were higher in follicular phase than in ovulatory and luteal phases.

Comparative Effectiveness of Targeted vs Empirical Antibiotic Prophylaxis to Prevent Sepsis from Transrectal Prostate Biopsy: A Retrospective Analysis

We compared the effectiveness of targeted prophylaxis to the effectiveness of empirical prophylaxis for preventing sepsis after transrectal prostate biopsy using a retrospective multicenter quality improvement study. A total of 13 Kaiser Permanente urology departments participated in a 1-year retrospective analysis of a quality improvement study. In the targeted prophylaxis group rectal cultures were performed before transrectal prostate biopsy and antibiotic sensitivities of Escherichia coli were used to guide the selection of a single agent antibiotic for prophylaxis. Cultures were plated on 10 μg/ml ciprofloxacin infused MacConkey agar at a central laboratory. Urologists using empirical prophylaxis continued the usual regimen of ciprofloxacin monotherapy prophylaxis but sometimes added an additional prophylactic antibiotic. The primary outcome of post-biopsy sepsis was compiled by a search of the electronic medical record for the appropriate ICD-9 codes. A total of 5,355 prostate biopsy procedures were performed between May 1, 2013 and April 30, 2014. Targeted prophylaxis was used in 1,802 procedures (34%) and empirical prophylaxis was used in 3,553 (66%). The overall incidence of post-biopsy sepsis was 0.52% (28 of 5,355 cases). The incidence of sepsis was 0.44% (8 of 1,802 cases) in the targeted prophylaxis group and 0.56% (20 of 3,553) in the empirical prophylaxis group (p = 0.568). The prevalence of ciprofloxacin resistant E. coli on rectal culture was 25% (444 of 1,802 cases). Seven of the 8 patients (88%) on targeted prophylaxis in whom sepsis developed used a prophylactic antibiotic to which the bacteria causing post-biopsy sepsis were sensitive. The targeted prophylaxis protocol enabled physicians to avoid using more than 1 broad-spectrum empirical antibiotic while simultaneously achieving an overall rate of sepsis similar to the rate seen with empirical prophylaxis.

Transrectal prostate biopsy-associated prophylaxis and infectious complications: report of a query to the emerging infections network of the infectious diseases society of america.

Background. Fluoroquinolone-resistant infections after transrectal prostate biopsy (TRPB) are increasing. Methods. Members of the Emerging Infections Network, a consortium of adult infectious diseases physicians sponsored by the Centers for Disease Control and Prevention and the Infectious Diseases Society of America, were administered an electronic 9-question survey regarding post-TRPB infections and associated prophylaxis. Results were compared with respondent characteristics. Results. The overall response rate was 47% (552 of 1180). Of the 552 respondents, 234 (42%) reported that this problem was not applicable to their practice. The remaining 318 (58%) reported that, despite widespread recent changes in prophylactic regimens, fluoroquinolone monotherapy still was most common, but diverse alternate or supplemental oral and parenteral antibiotics (including imipenem) also were used. Reports of culture-guided prophylaxis were rare (9%). The most common duration of prophylaxis was a single prebiopsy antibiotic dose. However, 16%-23% of respondents reported prophylaxis continuing for ≥24 hours postbiopsy. Post-TRPB infections were reported as being more frequent now than 4 years ago, with sepsis and genitourinary presentations predominating, but with osteomyelitis, endocarditis, and epidural abscess also occurring. Infection isolates reportedly were usually resistant to the prophylactic regimen. Conclusions. Emerging Infections Network members perceive post-TRPB infections as increasingly frequent, caused by resistant strains, and involving serious illness. Prophylactic approaches, although in flux, still usually entail ciprofloxacin monotherapy, which often is given for excessive durations. Multiple opportunities exist for infectious diseases specialists to partner with proceduralists in devising, studying, and implementing improved prophylaxis regimens for TRPB.

Oropharyngeal tularemia cases admitted to a military hospital in Ankara, Turkey

This study aimed to review the possible sources of infection of 16 oropharyngeal tularemia hospital cases, and to document their epidemiological and demographical characteristics, laboratory findings, treatment methods, and treatment results. Sixteen cases from a Turkish military hospital between January 2011 and December 2012 were retrospectively evaluated. The age, sex, occupation, place of residence, symptoms, duration of symptoms, laboratory results, treatment and duration, and treatment results were recorded. Tularemia was diagnosed through tularemia-specific tests once the other conditions that may have caused lymphadenopathy were excluded. Twelve of the patients included in this study were males. The average age of the patients was 32.1 ± 17.2 years. Sore throat, fatigue, and fever were the most frequent symptoms. The mean duration of symptoms was 21.6 ± 6.9 days. All the patients had been treated for tonsillopharyngitis in primary healthcare institutions previously. However, despite the treatment, cervical lymphadenopathy had developed in these cases. Patients were given streptomycin, doxycycline, and ciprofloxacin monotherapy or in combination. Ten of the cases fully recovered, while five required surgical lymph node drainage. Spontaneous drainage occurred in the single remaining case. Turkey is considered to be an endemic country with regards to tularemia. Prompt diagnosis and proper treatment of the disease is imperative in providing cure. Since it can be potentially confused with tuberculous lymphadenitis, differential diagnosis is vital. Patients presenting with a condition of tonsillopharyngitis in endemic areas must be carefully monitored.

Randomized double blind trial of ciprofloxacin prophylaxis during induction treatment in childhood acute lymphoblastic leukemia in the WK-ALL protocol in Indonesia.

ObjectivesToxic death is a big problem in the treatment of childhood acute lymphoblastic leukemia (ALL), especially in low-income countries. Studies of ciprofloxacin as single agent prophylaxis vary widely in success rate. We conducted a double-blind, randomized study to test the effects of ciprofloxacin monotherapy as prophylaxis for sepsis and death in induction treatment of the Indonesian childhood ALL protocol.MethodsPatients were randomized to the ciprofloxacin arm (n = 58) and to the placebo arm (n = 52). Oral ciprofloxacin monotherapy or oral placebo was administered twice a day. All events during induction were recorded: toxic death, abandonment, resistant disease, and complete remission rate.ResultsOf 110 patients enrolled in this study, 79 (71.8%) achieved CR. In comparison to the placebo arm, the ciprofloxacin arm had lower nadir of absolute neutrophil count during induction with median of 62 (range: 5–884) versus 270 (range: 14–25,480) × 109 cells/L (P < 0.01), greater risks for experiencing fever (50.0% versus 32.7%, P = 0.07), clinical sepsis (50.0% versus 38.5%, P = 0.22), and death (18.9% versus 5.8%, P = 0.05).ConclusionIn our setting, a reduced intensity protocol in a low-income situation, the data warn against using ciprofloxacin prophylaxis during induction treatment. A lower nadir of neutrophil count and higher mortality were found in the ciprofloxacin group.

Fluoroquinolones in Children With Fever and Neutropenia

There has been reluctance to use fluoroquinolones in children because of arthropathy in animal models; experience in pediatric fever and neutropenia (FN) has been limited. Our primary objective was to describe the effectiveness and safety of fluoroquinolones as empiric therapy for children with FN. We conducted electronic searches of Ovid Medline, EMBASE, the Cochrane Central Register of Controlled Trials, and limited studies to prospective pediatric trials in which any type of fluoroquinolone was administered as empiric therapy for FN. Of the 7281 reviewed articles, 10 were included in the meta-analysis that encompassed 740 episodes of FN. All studies consisted of low-risk FN episodes. The risk of treatment failure was 17% among those given ciprofloxacin monotherapy (n = 5 studies), 17% among those given nonciprofloxacin fluoroquinolone monotherapy (n = 2 studies), and 24% among those given fluoroquinolone combination therapy (n = 3 studies; P = 0.80). There were no cases of infectious deaths reported. Rates of sepsis and adverse events were very low. Experience with fluoroquinolones demonstrates excellent outcomes and short-term safety, although reported studies have been restricted to low-risk patients. Fluoroquinolones can be comfortably adopted for low-risk FN, although experience in high-risk FN is uncertain in pediatrics.

In vitro antibiotic susceptibility patterns of bacterial keratitis isolates in Oxford, UK: a 10-year review

To analyse the spectrum of bacterial keratitis isolates and their in vitro antibiotic susceptibilities over a 10-year period in Oxford, UK; and to compare the in vitro efficacy of ciprofloxacin with that of the combination of gentamicin and cefuroxime over the same period. All culture-positive corneal scrapes received from the Oxford Eye Hospital between July 1999 and June 2009 were identified retrospectively using a local microbiology database. For analysis of trends over time, the data was split into two equal 5-year periods. Statistical analysis was done using the χ² and Fisher exact tests. Over the 10-year study period, 467 corneal scrapes were performed of which 252 (54.0%) had positive bacterial cultures, growing a total of 267 organisms. The most commonly isolated bacteria were Staphylococci(40.1%) followed by Pseudomonasspecies (28.5%), other Gram-negative species (17.2%), Streptococci(7.1%), and Corynebacteria(6.0%). Between the first and second time periods there was an increase in the number of coagulase-negative Staphylococciand an increased resistance of the non-Pseudomonas Gram-negative group to chloramphenicol. Of the 189 isolates tested for sensitivity to both empirical antibiotic regimens, 176 (93.2%) were susceptible to ciprofloxacin whereas 188 (99.5%) were susceptible to either gentamicin or cefuroxime (P=0.0015). The spectrum of bacterial keratitis isolates and their in vitro antibiotic sensitivity patterns have generally remained stable over time. The combination of gentamicin and cefuroxime provides a broader spectrum of antimicrobial cover than ciprofloxacin monotherapy in Oxford, although both regimens continue to be appropriate choices for the initial management of this condition.

Mutant Selection Window and Characterization of Allelic Diversity for Ciprofloxacin-Resistant Mutants of Rhodococcus equi

The mutant prevention concentration (MPC) for ciprofloxacin was determined for two Rhodococcus equi strains. The MPC for both strains was 32 mug/ml, which is above the peak serum concentration of ciprofloxacin obtainable by oral administration in humans. Nine single nucleotide changes corresponding to eight amino acid substitutions in the quinolone resistance-determining regions of DNA gyrase subunits A and B were characterized. Only mutants with amino acid changes in Ser-83 of GyrA were highly resistant (>or=64 microg/ml). Our results suggest that ciprofloxacin monotherapy against R. equi infection may result in the emergence of ciprofloxacin-resistant mutants.

Treatment of Peritoneal Dialysis-Related Peritonitis with Ciprofloxacin Monotherapy: Clinical Outcomes and Bacterial Susceptibility over Two Decades

There is controversy about the preferred initial antibiotic therapy for peritoneal dialysis (PD)-related peritonitis. Quinolones have been used extensively in this setting, yet their long-term effectiveness is unknown. To analyze the results of a protocol of treatment of PD-related peritonitis with ciprofloxacin, maintained over two decades. We analyzed the clinical outcome of 682 episodes of bacterial peritonitis treated with intraperitoneal ciprofloxacin monotherapy, and the time course of bacterial susceptibility to this antimicrobial, in a historical cohort of 641 PD patients (1988-2007). Main outcome variables included changes to initial therapy and rates of hospital admission, catheter removal, relapse, reinfection, PD dropout, and mortality. For comparisons we divided the study period into phases A (1988-1994), B (1995-2000), and C (2001-2007). The incidence of Staphylococcus aureus peritonitis decreased, while the incidences of polymicrobial and negative-culture peritonitis increased after phase A. In vitro susceptibility to ciprofloxacin decreased significantly only among coagulase-negative staphylococci (87.0% susceptible strains in phase A vs 70.0% in B and 70.1% in C, p = 0.006). Overall success rates (catheter not removed and ongoing PD after the episode) remained stable, at over 85%. However, the proportion of patients treated solely with ciprofloxacin declined from 75.7% (A) to 47.3% (B) to 32.4% (C) (p < 0.0005) and admission rates increased from 12.7% to 16.8% to 24.9% respectively (p = 0.001). These changes affected all the etiologic groups except culture-negative peritonitis. In vitro resistance to ciprofloxacin was a marker of multiresistance and correlated strongly with clinical outcome of peritonitis. Among isolates susceptible to ciprofloxacin, changing initial therapy for any reason also predicted a poor outcome. Following satisfactory early results, the effectiveness of ciprofloxacin as monotherapy for PD-related peritonitis has declined markedly in the long term. This decline cannot be explained solely by a decrease of in vitro susceptibility to this antimicrobial, which was significant only among coagulase-negative staphylococci. Resistance to ciprofloxacin is a strong marker of in vitro multiresistance and poor clinical outcome of peritonitis.

Which reliable pharmacodynamic breakpoint should be advised for ciprofloxacin monotherapy in the hospital setting? A TDM-based retrospective perspective

To define in critically ill patients receiving intravenous (iv) ciprofloxacin (200 mg or 400 mg twice daily) and undergoing routine therapeutic drug monitoring (TDM) the interindividual pharmacokinetic variability and the reliable pharmacodynamic breakpoint enabled by these fixed dosing regimens according to the PK/PD principles and to the pattern of susceptibility to this antibiotic. Ciprofloxacin plasma concentrations [trough (Cmin) and 30 min post-dose peak (Cmax) levels] were analysed by means of an HPLC method. Optimal pharmacodynamic exposure was assessed by estimating the theoretical pharmacodynamic breakpoints (PD BP) for either Cmax or AUC. The final database included 177 sets of Cmin and Cmax performed in 89 patients (200 mg twice daily group, n=68; 400 mg twice daily group, n=21). A very wide interindividual scatter of results was observed for both the 200 mg group and the 400 mg group. Interestingly, for both groups only moderate log-linear relationships between estimated renal function (CLCR) on one hand and either Cmin (r2=0.08, 0.28) or estimated AUC24 (r2=0.10, 0.34) on the other hand were found. Median PD BP, respectively, in the 200 mg twice daily group and the 400 mg twice daily group, were 0.16 and 0.28 mg/L for Cmax, and 0.19 and 0.29 mg/L for AUC24. Lowering ciprofloxacin dosage in the presence of renal failure seems in most cases unnecessary, since drug accumulation occurred only in a few cases. Optimal pharmacodynamic exposure with fixed 200 or 400 mg twice daily regimens of ciprofloxacin may be ensured only against fully susceptible microorganisms with an MIC<0.3 mg/L. This supports the use of higher dosages in critically ill hospitalized patients, whereas the wide unpredictable interindividual pharmacokinetic variability suggests the usefulness of TDM with the intent of optimizing efficacy with ciprofloxacin therapy.