Ciprofloxacin :: therapeutic use
Latest Paper:
Department of Rehabilitation, Academic Medical Center Amsterdam, Meibergdreef 9, Amsterdam, The Netherlands. f.j.slim@amc.uva.nl
BACKGROUND/OBJECTIVE: To study the mechanism of nosocomial transmission of highly resistant microorganisms (HRMOs). DESIGN: A prospective observational study. SETTING: A spinal cord ward of a rehabilitation center. PARTICIPANTS: Patients admitted to the spinal cord rehabilitation ward. OUTCOME MEASURES: HRMOs present in urine and feces. HRMOs, Enterobacteriaceae:(1) that produced an extended-spectrum beta-lactamase (ESBL),(2) that were resistant to carbapenems,(3) that fluoroquinolones and aminoglycosides (for Escherichia coli and Klebsiella species), or other Enterobacteriaceae species that were resistant to 2 of 3 of the following types of antibiotics (fluoroquinolones, aminoglycosides, cotrimoxazole). METHODS: Bacterial growth, identification and sensitivity were tested in urine cultures of 46 patients and faeces cultures of 15 patients. Data were collected on demographic characteristics, underlying diseases, reason and date of admission, room number, method of catheterization (suprapubic, clean intermittent catheterization or indwelling Foley catheter) and antibiotic use. RESULTS: Nine different HRMOs (7 E. coli, 1 Enterobacter cloacae, and 1 Citrobacter koseri) were isolated in urine samples from 15 patients. E. coli resistant to gentamicin, tetracycline, amoxicillin, cotrimoxazole, and ciprofloxacin were isolated from 8 patients during the study (cluster 1). One strain of multiresistant E coli found before the start of the study was not found during the study period (cluster 2). E coli strains producing an ESBL and resistant to tetracycline, cotrimoxazole, and ciprofloxacin were isolated from urine samples of 3 patients (cluster 3). Ciprofloxacin-resistant E. coli were present in feces of 3 patients (2 in cluster 1). Catheterization was found to be significantly more prevalent in patients with HRMOs. Most of the patients in cluster 1 were treated with antibiotics before the first isolation of the strain. CONCLUSIONS: HRMOs from urine samples were strongly correlated with the use of catheterization. A close correlation was found between prior use of antibiotics and colonization of the urinary tract on the level of the individual patient, which has been rarely described in the literature.
Mesh-terms: Adult; Aged; Aged, 80 and over; Anti-Infective Agents :: therapeutic use; Ciprofloxacin :: therapeutic use; Cross Infection :: drug therapy; Cross Infection :: epidemiology; Cross Infection :: etiology; Cross Infection :: microbiology; Drug Resistance, Multiple, Bacterial :: drug effects; Escherichia coli :: drug effects; Escherichia coli :: isolation & purification; Feces :: microbiology; Female; Humans; Male; Microbial Sensitivity Tests :: methods; Middle Aged; Prospective Studies; Rehabilitation Centers :: statistics & numerical data; Spinal Cord Injuries :: microbiology; Spinal Cord Injuries :: urine;
Most cited papers:
Center for Clinical Pharmacy Research, School of Pharmacy, State University of New York, Buffalo 14260.
Seventy-four acutely ill patients were treated with intravenous ciprofloxacin at dosages ranging between 200 mg every 12 h and 400 mg every 8 h. A population pharmacokinetic-pharmacodynamic analysis relating drug exposure (and other factors) to infectious outcome was performed. Plasma samples were obtained and assayed for ciprofloxacin by high-performance liquid chromatography. Samples from patients were frequently cultured so that the day of bacterial eradication could be determined. The pharmacokinetic data were fitted by iterative two-stage analysis, assuming a linear two-compartment model. Logistic regression was used to model ciprofloxacin exposure (and other potential covariates) versus the probabilities of achieving clinical and microbiologic cures. The same variables were also modelled versus the time to bacterial eradication by proportional hazards regression. The independent variables considered were dose, site of infection, infecting organism and the MIC for it, percent time above the MIC, peak, peak/MIC ratio, trough, trough/MIC ratio, 24-h area under the concentration-time curve (AUC), AUC/MIC ratio (AUIC), presence of other active antibacterial agents, and patient characteristics. The most important predictor for all three measures of ciprofloxacin pharmacodynamics was the AUIC. A 24-h AUIC of 125 SIT-1.h (inverse serum inhibitory titer integrated over time) was found to be a significant breakpoint for probabilities of both clinical and microbiologic cures. At an AUIC below 125 (19 patients), the percent probabilities of clinical and microbiologic cures were 42 and 26%, respectively. At an AUIC above 125 (45 patients), the probabilities were 80%(P < .005) and 82%(P < .001), respectively. There were two significant breakpoints in the time-to-bacterial-eradication data. At an AUIC below 125 (21 patients), the median time to eradication exceeded 32 days; at an AUIC of 125 to 250 (15 patients), time to eradication was 6.6 days: and at AUIC above 250 (28 patients), the median time to eradication was 1.9 days (groups differed; P < .005). These findings, when combined with pharmacokinetic data reported in the companion article, provide the rationale and tools needed for targeting the dosage of intravenous ciprofloxacin to individual patients' pharmacokinetics and their bacterial pathogens' susceptibilities. An a priori dosing algorithm (based on MIC, patient creatine clearance and weight, and the clinician-specified AUIC target) was developed. This approach was shown, retrospectively, to be more precise than current guidelines, and it can be used to achieve more rapid bacteriologic and clinical responses to ciprofloxacin, as a consequence of targeting the AUIC.
Mesh-terms: Adult; Aged; Aged, 80 and over; Algorithms; Analysis of Variance; Bacterial Infections :: drug therapy; Ciprofloxacin :: pharmacokinetics; Ciprofloxacin :: pharmacology; Ciprofloxacin :: therapeutic use; Critical Illness; Drug Administration Schedule; Female; Human; Male; Middle Aged; Multivariate Analysis; Probability; Prospective Studies; Treatment Outcome;
The purpose of this study was to determine the impact of a scheduled change of antibiotic classes, used for the empiric treatment of suspected gram-negative bacterial infections, on the incidence of ventilator-associated pneumonia and nosocomial bacteremia. Six hundred eighty patients undergoing cardiac surgery were evaluated. During a 6-mo period (i.e., the before-period), our traditional practice of prescribing a third generation cephalosporin (ceftazidime) for the empiric treatment of suspected gram-negative bacterial infections was continued. This was followed by a 6-mo period (i.e., the after-period) during which a quinolone (ciprofloxacin) was used in place of the third-generation cephalosporin. The incidence of ventilator-associated pneumonia was significantly decreased in the after-period (n = 327) compared with the before-period (n = 353)(6.7 versus 11.6%; p = .028). This was primarily due to a significant reduction in the incidence of ventilator-associated pneumonia attributed to antibiotic-resistant gram-negative bacteria ( .9 versus 4. %; p = .013). Similarly, we observed a lower incidence of bacteremia attributed to antibiotic-resistant gram-negative bacteria in the after-period compared with the before-period ( .3 versus 1.7%; p = .125). These data suggest that a scheduled change of antibiotic classes can reduce the incidence of ventilator-associated pneumonia attributed to antibiotic-resistant gram-negative bacteria.
Mesh-terms: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Infective Agents :: administration & dosage; Anti-Infective Agents :: therapeutic use; Bacteremia :: drug therapy; Bacteremia :: etiology; Ceftazidime :: administration & dosage; Ceftazidime :: therapeutic use; Cephalosporin Resistance; Cephalosporins :: administration & dosage; Cephalosporins :: therapeutic use; Ciprofloxacin :: therapeutic use; Comparative Study; Drug Administration Schedule; Female; Gram-Negative Bacteria :: drug effects; Gram-Negative Bacterial Infections :: drug therapy; Gram-Negative Bacterial Infections :: etiology; Hospital Mortality; Human; Incidence; Male; Middle Aged; Pneumonia, Bacterial :: drug therapy; Pneumonia, Bacterial :: etiology; Prospective Studies; Respiration, Artificial :: adverse effects; Support, Non-U.S. Gov't;
Department of Medicine, Olive View-UCLA Medical Center, University of California, Los Angeles 91342, USA. idnet@ucla.edu
CONTEXT: The optimal antimicrobial regimen and treatment duration for acute uncomplicated pyelonephritis are unknown. OBJECTIVE: To compare the efficacy and safety of a 7-day ciprofloxacin regimen and a 14-day trimethoprim-sulfamethoxazole regimen for the treatment of acute pyelonephritis in women. DESIGN: Randomized, double-blind comparative trial conducted from October 1994 through January 1997. SETTING: Twenty-five outpatient centers in the United States. PATIENTS: Of 378 enrolled premenopausal women aged at least 18 years with clinical diagnosis of acute uncomplicated pyelonephritis, 255 were included in the analysis. Other individuals were excluded for no baseline causative organism, inadequate receipt of study drug, loss to follow-up, no appropriate cultures, and other reasons. INTERVENTIONS: Patients were randomized to oral ciprofloxacin, 500 mg twice per day for 7 days (with or without an initial 400-mg intravenous dose) followed by placebo for 7 days (n = 128 included in analysis) vs trimethoprim-sulfamethoxazole, 160/800 mg twice per day for 14 days (with or without intravenous ceftriaxone, 1 g)(n = 127 included in the analysis). MAIN OUTCOME MEASURE: Continued bacteriologic and clinical cure, such that alternative antimicrobial drugs were not required, among evaluable patients through the 4- to 11-day posttherapy visit, compared by treatment group. RESULTS: At 4 to 11 days posttherapy, bacteriologic cure rates were 99%(112 of 113) for the ciprofloxacin regimen and 89%(90 of 101) for the trimethoprim-sulfamethoxazole regimen (95% confidence interval [CI] for difference, .04- .16; P =.004). Clinical cure rates were 96%(109 of 113) for the ciprofloxacin regimen and 83%(92 of 111) for the trimethoprim-sulfamethoxazole regimen (95% CI, .06- .22; P =.002). Escherichia coli, which caused more than 90% of infections, was more frequently resistant to trimethoprim-sulfamethoxazole (18%) than to ciprofloxacin ( %; P<.001). Among trimethoprim-sulfamethoxazole-treated patients, drug resistance was associated with greater bacteriologic and clinical failure rates (P<.001 for both). Drug-related adverse events occurred in 24% of 191 ciprofloxacin-treated patients and in 33% of 187 trimethoprim-sulfamethoxazole-treated patients, respectively (95% CI,- .001 to .2). CONCLUSIONS: In our study of outpatient treatment of acute uncomplicated pyelonephritis in women, a 7-day ciprofloxacin regimen was associated with greater bacteriologic and clinical cure rates than a 14-day trimethoprim-sulfamethoxazole regimen, especially in patients infected with trimethoprim-sulfamethoxazole-resistant strains.
Mesh-terms: Acute Disease; Adult; Anti-Infective Agents :: administration & dosage; Anti-Infective Agents :: economics; Anti-Infective Agents :: therapeutic use; Anti-Infective Agents, Urinary :: administration & dosage; Anti-Infective Agents, Urinary :: economics; Anti-Infective Agents, Urinary :: therapeutic use; Ciprofloxacin :: administration & dosage; Ciprofloxacin :: economics; Ciprofloxacin :: therapeutic use; Comparative Study; Double-Blind Method; Drug Administration Schedule; Drug Resistance, Microbial; Female; Health Care Costs; Human; Middle Aged; Pyelonephritis :: drug therapy; Pyelonephritis :: economics; Pyelonephritis :: microbiology; Support, Non-U.S. Gov't; Trimethoprim-Sulfamethoxazole Combination :: administration & dosage; Trimethoprim-Sulfamethoxazole Combination :: economics; Trimethoprim-Sulfamethoxazole Combination :: therapeutic use;
Department of Medicine, Emory University School of Medicine, Atlanta, GA 30303.
The fluoroquinolones, particularly ciprofloxacin, have been suggested to treat methicillin-resistant Staphylococcus aureus (MRSA) infections and colonization and methicillin-susceptible S. aureus (MSSA) infections. The development of ciprofloxacin resistance in MRSA and MSSA was prospectively evaluated. After 3 months of ciprofloxacin use, high-level resistance (MIC90, 64 micrograms/ml) developed in MRSA and increased at an alarming rate, from none to 79% over a 1-year period. High-level ciprofloxacin resistance also developed in MSSA, increasing to 13.6% over the same period. Antibiograms, phage typing, and plasmid profile analysis suggest that more than one clone of MRSA developed resistance and that ciprofloxacin resistance is not associated with the acquisition of a new plasmid. Most patients had nosocomial acquisition and about one-half had a history of previous ciprofloxacin use. Ciprofloxacin resistance can develop rapidly in S. aureus; thus, ciprofloxacin appears to have limited usefulness in treating staphylococcal infections and colonization, especially those due to MRSA.
Mesh-terms: Ciprofloxacin :: pharmacology; Ciprofloxacin :: therapeutic use; Drug Resistance, Microbial :: genetics; Human; Methicillin Resistance; Microbial Sensitivity Tests; Prospective Studies; R Factors; Staphylococcal Infections :: drug therapy; Staphylococcal Infections :: microbiology; Staphylococcus aureus :: drug effects; Staphylococcus aureus :: genetics;
Servicio de Medicina Interna-Patologia Infecciosa, Hospital General Vall d'Hebrón, Autonomous University of Barcelona, Spain.
Thirty-six Permcath double-lumen catheters implanted in 36 chronic renal failure patients for haemodialysis treatment were prospectively studied. When catheter-related sepsis was suspected a quantitative blood culture was obtained simultaneously from the catheter and from a peripheral vein. If bacterial colonies in the catheter blood specimen were fourfold greater than identical bacterial colonies in the peripheral blood specimen, the test was considered indicative of catheter sepsis and an empirical antibiotic regimen was begun while the central line remained in situ. Eleven patients suffered 13 episodes of catheter-related sepsis. Staphylococcus epidermidis and Pseudomonas aeruginosa accounted for 77% of the strains isolated. All episodes were successfully treated with vancomycin or ciprofloxacin and yielded negative results on follow-up quantitative blood cultures. Fever subsided within the first 48 h of therapy and no complications occurred. None of these patients required catheter removal for cure of the catheter-related sepsis.
Mesh-terms: Adult; Aged; Aged, 80 and over; Bacteremia :: drug therapy; Bacteremia :: etiology; Catheterization, Central Venous :: adverse effects; Catheters, Indwelling; Ciprofloxacin :: therapeutic use; Female; Human; Jugular Veins; Male; Middle Aged; Prospective Studies; Pseudomonas Infections :: drug therapy; Pseudomonas Infections :: etiology; Renal Dialysis; Staphylococcal Infections :: drug therapy; Staphylococcal Infections :: etiology; Staphylococcus epidermidis; Support, Non-U.S. Gov't; Vancomycin :: therapeutic use;
ADIS Drug Information Services, Auckland.
Ciprofloxacin is one of a new generation of fluorinated quinolones structurally related to nalidixic acid. The primary mechanism of action of ciprofloxacin is inhibition of bacterial DNA gyrase. It is a broad spectrum antibacterial drug to which most Gram-negative bacteria are highly susceptible in vitro and many Gram-positive bacteria are susceptible or moderately susceptible. Unlike most broad spectrum antibacterial drugs, ciprofloxacin is effective after oral or intravenous administration. Ciprofloxacin has been most extensively studied following oral administration. It attains concentrations in most tissues and body fluids which are at least equivalent to the minimum inhibitory concentration designated as the breakpoint for bacterial susceptibility in vitro. The results of clinical trials with orally and intravenously administered ciprofloxacin have confirmed the potential for its use in a wide range of infections, which was suggested by its in vitro antibacterial and pharmacokinetic profiles. It has proven an effective treatment for many types of systemic infections as well as for both acute and chronic infections of the urinary tract. Ciprofloxacin generally appeared to be at least as effective as alternative orally administered antibacterial drugs in the indications in which they were compared, and in some indications, to parenterally administered antibacterial therapy. However, further studies are needed to fully clarify the comparative efficacy of ciprofloxacin and standard antibacterial therapies. Bacterial resistance to ciprofloxacin develops infrequently, both in vitro and clinically, except in the setting of pseudomonal respiratory tract infections in cystic fibrosis patients. The drug is also well tolerated. Thus, as an orally active, broad spectrum and potent antibacterial drug, ciprofloxacin offers a valuable alternative to broad spectrum parenterally administered antibacterial drugs for use in a wide range of clinical infections, including difficult infections due to multiresistant pathogens.
Division of HIV/AIDS, Centers for Disease Control, Atlanta, GA 30333.
The contribution of disseminated Mycobacterium avium complex (DMAC) infection to the morbidity and mortality of patients with acquired immune deficiency syndrome (AIDS) is unclear. Previous studies that suggested the decreased survival of patients with AIDS and DMAC had incomplete information on patient immunologic status and follow-up. We studied patients with AIDS and DMAC and compared their survival with that of AIDS patients without DMAC but with other comparable risk factors for survival. Case and control subjects were similar in terms of CD4 cell count, prior AIDS status, history of antiretroviral therapy, history of Pneumocystis carinii prophylaxis, and year of diagnosis. A group of 39 patients with untreated DMAC had significantly shorter survival, mean of 5.6 +/- 1.1 months (median 4 months), than 39 matched patients with AIDS but without DMAC, mean 10.8 +/- 1.3 months (median 11 months, p less than .0001). The survival of 16 additional patients with DMAC who received antimycobacterial therapy, mean of 9.5 +/- 1.4 months (median 8 months), was not significantly shorter than that of an additional 16 matched control subjects, mean 11.7 +/- 1.9 months (median 11 months, p = .58). Patients with treated DMAC survived significantly longer than those with untreated DMAC (p less than .01). We conclude that untreated DMAC significantly shortens survival. Moreover, these results indicate that patients with DMAC who receive antimycobacterial therapy do not experience the shortened survival seen in untreated DMAC.
Mesh-terms: Acquired Immunodeficiency Syndrome :: complications; Acquired Immunodeficiency Syndrome :: mortality; Anti-Bacterial Agents :: therapeutic use; Antibiotics, Antitubercular :: therapeutic use; Ciprofloxacin :: therapeutic use; Clofazimine :: therapeutic use; Human; Mycobacterium avium-intracellulare Infection :: complications; Mycobacterium avium-intracellulare Infection :: drug therapy; Mycobacterium avium-intracellulare Infection :: pathology; Survival Rate;
J S Solomkin,
H H Reinhart,
E P Dellinger,
J M Bohnen,
O D Rotstein,
S B Vogel,
H H Simms,
C S Hill,
H S Bjornson,
D C Haverstock,
H O Coulter,
R M Echols
Department of Surgery, University of Cincinnati College of Medicine, Ohio, 45267-0558, USA.
OBJECTIVE: In a randomized, double-blind, multicenter trial, ciprofloxacin/metronidazole was compared with imipenem/cilastatin for treatment of complicated intra-abdominal infections. A secondary objective was to demonstrate the ability to switch responding patients from intravenous (IV) to oral (PO) therapy. SUMMARY BACKGROUND DATA: Intra-abdominal infections result in substantial morbidity, mortality, and cost. Antimicrobial therapy often includes a 7- to 10-day intravenous course. The use of oral antimicrobials is a recent advance due to the availability of agents with good tissue pharmacokinetics and potent aerobic gram-negative activity. METHODS: Patients were randomized to either ciprofloxacin plus metronidazole intravenously (CIP/MTZ IV) or imipenem intravenously (IMI IV) throughout their treatment course, or ciprofloxacin plus metronidazole intravenously and treatment with oral ciprofloxacin plus metronidazole when oral feeding was resumed (CIP/MTZ IV/PO). RESULTS: Among 671 patients who constituted the intent-to-treat population, overall success rates were as follows: 82% for the group treated with CIP/MTZ IV; 84% for the CIP/MTZ IV/PO group; and 82% for the IMI IV group. For 330 valid patients, treatment success occurred in 84% of patients treated with CIP/MTZ IV, 86% of those treated with CIP/MTZ IV/PO, and 81% of the patients treated with IMI IV. Analysis of microbiology in the 30 patients undergoing intervention after treatment failure suggested that persistence of gram-negative organisms was more common in the IMI IV-treated patients who subsequently failed. Of 46 CIP/MTZ IV/PO patients (active oral arm), treatment success occurred in 96%, compared with 89% for those treated with CIP/MTZ IV and 89% for those receiving IMI IV. Patients who received intravenous/oral therapy were treated, overall, for an average of 8.6 +/- 3.6 days, with an average of 4. +/- 3. days of oral treatment. CONCLUSIONS: These results demonstrate statistical equivalence between CIP/MTZ IV and IMI IV in both the intent-to-treat and valid populations. Conversion to oral therapy with CIP/MTZ appears as effective as continued intravenous therapy in patients able to tolerate oral feedings.
Mesh-terms: Abdomen; Administration, Oral; Adolescent; Adult; Aged; Anti-Infective Agents :: therapeutic use; Antibiotics, Combined :: therapeutic use; Cilastatin :: therapeutic use; Ciprofloxacin :: therapeutic use; Comparative Study; Double-Blind Method; Human; Imipenem :: therapeutic use; Infection :: drug therapy; Infection :: microbiology; Infusions, Intravenous; Metronidazole :: therapeutic use; Middle Aged; Treatment Outcome;
A combination of ciprofloxacin (intravenous then oral) and oral rifampicin was tested in 14 intravenous drug users with right-sided Staphylococcus aureus endocarditis. All 10 patients who completed therapy were cured based on resolution of symptoms and negative blood cultures at 4 weeks post therapy.
Mesh-terms: Adult; Ciprofloxacin :: administration & dosage; Ciprofloxacin :: therapeutic use; Drug Administration Schedule; Drug Therapy, Combination; Echocardiography; Endocarditis, Bacterial :: drug therapy; Endocarditis, Bacterial :: etiology; Endocarditis, Bacterial :: microbiology; Female; Follow-Up Studies; Human; Male; Pilot Projects; Rifampin :: administration & dosage; Rifampin :: therapeutic use; Staphylococcal Infections :: drug therapy; Staphylococcal Infections :: etiology; Staphylococcal Infections :: microbiology; Substance Abuse, Intravenous :: complications;
