Inhaled antibiotics for pulmonary exacerbations in cystic fibrosis.

BACKGROUND: Cystic fibrosis is a genetic disorder in which abnormal mucus in the lungs is associated with susceptibility to persistent infection. Pulmonary exacerbations are when symptoms of infection become more severe. Antibiotics are an essential part of treatment for exacerbations and inhaled antibiotics may be used alone or in conjunction with oral antibiotics for milder exacerbations or with intravenous antibiotics for more severe infections. Inhaled antibiotics do not cause the same adverse effects as intravenous antibiotics and may prove an alternative in people with poor access to their veins. This is an update of a previously published review. OBJECTIVES: To determine if treatment of pulmonary exacerbations with inhaled antibiotics in people with cystic fibrosis improves their quality of life, reduces time off school or work and improves their long-term survival. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis Group's Cystic Fibrosis Trials Register. Date of the last search: 03 October 2018.We searched ClinicalTrials.gov, the Australia and New Zealand Clinical Trials Registry and WHO ICTRP for relevant trials. Date of last search: 09 October 2018. SELECTION CRITERIA: Randomised controlled trials in people with cystic fibrosis with a pulmonary exacerbation in whom treatment with inhaled antibiotics was compared to placebo, standard treatment or another inhaled antibiotic for between one and four weeks. DATA COLLECTION AND ANALYSIS: Two review authors independently selected eligible trials, assessed the risk of bias in each trial and extracted data. They assessed the quality of the evidence using the GRADE criteria. Authors of the included trials were contacted for more information. MAIN RESULTS: Four trials with 167 participants are included in the review. Two trials (77 participants) compared inhaled antibiotics alone to intravenous antibiotics alone and two trials (90 participants) compared a combination of inhaled and intravenous antibiotics to intravenous antibiotics alone. Trials were heterogenous in design and two were only available in abstract form. Risk of bias was difficult to assess in most trials, but for all trials we judged there to be a high risk from lack of blinding and an unclear risk with regards to randomisation. Results were not fully reported and only limited data were available for analysis.Inhaled antibiotics alone versus intravenous antibiotics aloneOnly one trial (n = 18) reported a perceived improvement in lifestyle (quality of life) in both groups (very low-quality of evidence). Neither trial reported on time off work or school. Both trials measured lung function, but there was no difference reported between treatment groups (very low-quality evidence). With regards to our secondary outcomes, one trial (n = 18) reported no difference in the need for additional antibiotics and the second trial (n = 59) reported on the time to next exacerbation. In neither case was a difference between treatments identified (both very low-quality evidence). The single trial (n = 18) measuring adverse events and sputum microbiology did not observe any in either treatment group for either outcome (very low-quality evidence).Inhaled antibiotics plus intravenous antibiotics versus intravenous antibiotics aloneNeither trial reported on quality of life or time off work or school. Both trials measured lung function, but found no difference between groups in forced expiratory volume in one second (one trial, n = 28, very low-quality evidence) or vital capacity (one trial, n = 62). Neither trial reported on the need for additional antibiotics or the time to the next exacerbation; however, one trial (n = 28) reported on hospital admissions and found no difference between groups. Both trials reported no difference between groups in adverse events (very low-quality evidence) and one trial (n = 62) reported no difference in the emergence of antibiotic-resistant organisms (very low-quality evidence). AUTHORS' CONCLUSIONS: There is little useful high-level evidence to judge the effectiveness of inhaled antibiotics for the treatment of pulmonary exacerbations in people with cystic fibrosis. The included trials were not sufficiently powered to achieve their goals. Hence, we are unable to demonstrate whether one treatment was superior to the other or not. Further research is needed to establish whether inhaled tobramycin may be used as an alternative to intravenous tobramycin for some pulmonary exacerbations.

Metal-carbenicillin framework-based nanoantibiotics with enhanced penetration and highly efficient inhibition of MRSA.

The development of effective therapies to control methicillin-resistant Staphylococcus aureus (MRSA) infections is challenging because antibiotics can be degraded by the production of certain enzymes, for example, ß-lactamases. Additionally, the antibiotics themselves fail to penetrate the full depth of biofilms formed from extracellular polymers. Nanoparticle-based carriers can deliver antibiotics with better biofilm penetration, thus combating bacterial resistance. In this study, we describe a general approach for the construction of ß-lactam antibiotics and ß-lactamase inhibitors co-delivery of nanoantibiotics based on metal-carbenicillin framework-coated mesoporous silica nanoparticles (MSN) to overcome MRSA. Carbenicillin, a ß-lactam antibiotic, was used as an organic ligand that coordinates with Fe3+ to form a metal-carbenicillin framework to block the pores of the MSN. Furthermore, these ß-lactamase inhibitor-loaded nanoantibiotics were stable under physiological conditions and could synchronously release antibiotic molecules and inhibitors at the bacterial infection site to achieve a better elimination of antibiotic resistant bacterial strains and biofilms. We confirmed that these ß-lactamase inhibitor-loaded nanoantibiotics had better penetration depth into biofilms and an obvious effect on the inhibition of MRSA both in vitro and in vivo.

Nebuliser systems for drug delivery in cystic fibrosis.

BACKGROUND: Nebuliser systems are used to deliver medications to control the symptoms and the progression of lung disease in people with cystic fibrosis. Many types of nebuliser systems are available for use with various medications; however, there has been no previous systematic review which has evaluated these systems. OBJECTIVES: To evaluate effectiveness, safety, burden of treatment and adherence to nebulised therapy using different nebuliser systems for people with cystic fibrosis. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches, handsearching of relevant journals and abstract books of conference proceedings. We searched the reference lists of each study for additional publications and approached the manufacturers of both nebuliser systems and nebulised medications for published and unpublished data. Date of the most recent search: 15 Oct 2012. SELECTION CRITERIA: Randomised controlled trials or quasi-randomised controlled trials comparing nebuliser systems including conventional nebulisers, vibrating mesh technology systems, adaptive aerosol delivery systems and ultrasonic nebuliser systems. DATA COLLECTION AND ANALYSIS: Two authors independently assessed studies for inclusion. They also independently extracted data and assessed the risk of bias. A third author assessed studies where agreement could not be reached. MAIN RESULTS: The search identified 40 studies with 20 of these (1936 participants) included in the review. These studies compared the delivery of tobramycin, colistin, dornase alfa, hypertonic sodium chloride and other solutions through the different nebuliser systems. This review demonstrates variability in the delivery of medication depending on the nebuliser system used. Conventional nebuliser systems providing higher flows, higher respirable fractions and smaller particles decrease treatment time, increase deposition and may be preferred by people with CF, as compared to conventional nebuliser systems providing lower flows, lower respirable fractions and larger particles. Nebulisers using adaptive aerosol delivery or vibrating mesh technology reduce treatment time to a far greater extent. Deposition (as a percentage of priming dose) is greater than conventional with adaptive aerosol delivery. Vibrating mesh technology systems may give greater deposition than conventional when measuring sputum levels, but lower deposition when measuring serum levels or using gamma scintigraphy. The available data indicate that these newer systems are safe when used with an appropriate priming dose, which may be different to the priming dose used for conventional systems. There is an indication that adherence is maintained or improved with systems which use these newer technologies, but also that some nebuliser systems using vibrating mesh technology may be subject to increased failures. AUTHORS' CONCLUSIONS: Clinicians should be aware of the variability in the performance of different nebuliser systems. Technologies such as adaptive aerosol delivery and vibrating mesh technology have advantages over conventional systems in terms of treatment time, deposition as a percentage of priming dose, patient preference and adherence. There is a need for long-term randomised controlled trials of these technologies to determine patient-focused outcomes (such as quality of life and burden of care), safe and effective dosing levels of medications and clinical outcomes (such as hospitalisations and need for antibiotics) and an economic evaluation of their use.

Antibiotic loading on bioactive glasses and glass-ceramics: an approach to surface modification.

A bioactive glass and its corresponding glass-ceramic have been used to investigate the possibility to load a common antibiotic (carbenicillin) on their surface during the reactivity processes which occur by dipping these materials in a simulated body fluid. The materials bioactivity in the early stage of simulated body fluid treatment has been investigated by means of scanning electron microscopy (SEM-EDS) and X-ray diffraction. The uptake of carbenicillin has been performed by dipping the samples in simulated body fluid solution with a drug concentration of 500 mg/l for 6, 12 and 24 h. Some glass samples underwent a pre-treatment in simulated body fluid, for different time frames, in order to form a silica gel layer before the surface exposition to antibiotic. The carbenicillin release has been measured in water up to 36 h. The amount of incorporated and released antibiotic has been estimated by UV visible spectrophotometer. All samples were able to incorporate a significant amount of antibiotic and it was possible to tailor the drug release by modifying the simulated body fluid pre-treatment.

Inhaled antibiotics for pulmonary exacerbations in cystic fibrosis.

BACKGROUND: Cystic fibrosis is a genetic disorder in which abnormal mucus in the lungs is associated with susceptibility to persistent infection. Pulmonary exacerbations are when symptoms of infection become more severe. Antibiotics are an essential part of treatment for exacerbations and inhaled antibiotics may be used alone or in conjunction with oral antibiotics for milder exacerbations or with intravenous antibiotics for more severe infections. Inhaled antibiotics do not cause the same adverse effects as intravenous antibiotics and may prove an alternative in people with poor access to their veins. OBJECTIVES: To determine if treatment of pulmonary exacerbations with inhaled antibiotics in people with cystic fibrosis improves their quality of life, reduces time off school or work and improves their long-term survival. SEARCH METHODS: We searched ClinicalTrials.gov and the Australia and New Zealand Clinical Trials Registry for relevant trials. Date of last search: 15 March 2012We also searched the Cochrane Cystic Fibrosis Group's Cystic Fibrosis Trials Register. Date of the last search: 01 June 2012. SELECTION CRITERIA: Randomised controlled trials in people with cystic fibrosis with a pulmonary exacerbation in whom treatment with inhaled antibiotics was compared to placebo, standard treatment or another inhaled antibiotic for between one and four weeks. DATA COLLECTION AND ANALYSIS: Two review authors independently selected eligible trials, assessed the risk of bias in each trial and extracted data. Authors of the included trials were contacted for more information. MAIN RESULTS: Six trials with 208 participants were included in the review. Trials were heterogenous in design and interventions (however, all included trials compared inhaled versus intravenous antibiotic regimens). Risk of bias was difficult to assess in most trials. Results were not fully reported and only limited data were available for analysis. Four trials reported some results on forced expiratory volume at one second and found no significant differences between the inhaled antibiotic and the comparison intervention. In two of these trials using 300 mg of inhaled tobramycin, the change in forced expiratory volume at one second was similar to intravenous tobramycin; and in one trial the time until the next exacerbation was not different. No important adverse effects were reported. AUTHORS' CONCLUSIONS: There is little useful high-level evidence to judge the effectiveness of inhaled antibiotics for the treatment of pulmonary exacerbations in people with cystic fibrosis. The included trials were not sufficiently powered to achieve their goals. Hence, we are unable to demonstrate whether one treatment was superior to the other or not. Further research is needed to establish whether inhaled tobramycin may be used as an alternative to intravenous tobramycin for some pulmonary exacerbations.

[Anti-Pseudomonas aerosol therapy in cystic fibrosis: improvement with tobramycin]. / Aérosolthérapie anti-pyocyanique dans la mucoviscidose: apport de la tobramycine.

Aerosol delivery of antibiotics offers the potential to achieve high antibiotic concentrations at the site of infection while reducing the risk of systemic untoward effects because of minimal resorption into the bloodstream. We reviewed knowledge acquired in this field over the two latter decades. While the earliest data were obtained with gentamycin, the most conclusive evidence presently regards aminoglycosides and colistin. Aerosol delivery of tobramycin was recently improved with the development of a new formulation for inhalation. Coupled with an adequate nebulization system, intermittent treatment with tobramycin for inhalation has been evaluated in randomized placebo-controlled studies. These studies have demonstrated a significant improvement of respiratory function.

Empirical antimicrobial therapy in pediatric patients with neutropenia and fever. Risk factor for treatment failure

Background. The use of combinations of antibiotics has been the cornerstone of therapy for febrile patients with cancer and severe neutropenia. Each empirical regimen should be selected according to the epidemiology and susceptibility patterns in each center. We describe here the experience wtih empirical antimicrobiial treatments in pediatric patients with cancer, fever and severe neutropenia, and identify the risk factors associated with treatment failure. Methods. This is a prospective study including 145 patients with cancer, and 171 episodes of neutropenia and fever. Blood cultures were taken before initiating empirical treatment: a)carbenicillin (400 mg/kg/day) plus amikacin (21 mg/kg/day) (Cb/ak), and b) ceftazidime (100 mg/kg/day), plus amikacin at the same dosage (Cz/ak). Results. The overall response rate was 54.9 percent and 56.3 percent for Cb/ak and Cz/ak, respectively. Fifty-seven episodes (33.3 percent) were microbiologically documented, gram-positive isolated in 38 percent and gram-negative in 49 percent. Risk factors associated significantly with treatment failure were acute mywlocytic leukemia (AML) (RR 2.59, CI 95 percent 1.42-4.7, p=0.003); bacteriological identification (RR= 4.41, CI 95 percent 2.21 - 8.8, p<0.001), and the presence of two or more sites of infection (RR= 2.89, CI 95 percent 1.03 - 8.11, p=0.03). Conclusions. The rates of response are similar to the combinations used in the hospital (Cb/ak, Cz/ak). The risk factors associated with treatment failure were AML diagnosis, bacteriological identification, and the presence of two or more sites of infection

Empirical antimicrobial therapy in pediatric patients with neutropenia and fever. Risk factors for treatment failure.

BACKGROUND: The use of combinations of antibiotics has been the cornerstone of therapy for febrile patients with cancer and severe neutropenia. Each empirical regimen should be selected according to the epidemiology and susceptibility patterns in each center. We describe here the experience with empirical antimicrobial treatments in pediatric patients with cancer, fever and severe neutropenia, and identify the risk factors associated with treatment failure. METHODS: This is a prospective study including 145 patients with cancer, and 171 episodes of neutropenia and fever. Blood cultures were taken before initiating empirical treatment: a) carbenicillin (400 mg/kg/day) plus amikacin (21 mg/kg/day) (Cb/ak), and b) ceftazidime (100 mg/kg/day), plus amikacin at the same dosage (Cz/ak). RESULTS: The overall response rate was 54.9% and 56.3% for Cb/ak and Cz/ak, respectively. Fifty-seven episodes (33.3%) were microbiologically documented, gram-positive isolated in 38% and gram-negative in 49%. Risk factors associated significantly with treatment failure were acute myelocytic leukemia (AML) (RR 2.59, CI 95% 1.42-4.7, p = 0.003); bacteriological identification (RR = 4.41, CI 95% 2.21-8.8, p < 0.001), and the presence of two or more sites of infection (RR = 2.89, CI 95% 1.03-8.11, p = 0.03). CONCLUSIONS: The rates of response are similar to the combinations used in the hospital (Cb/ak, Cz/ak). The risk factors associated with treatment failure were AML diagnosis, bacteriological identification, and the presence of two or more sites of infection.

The effect of the renal portal system on pharmacokinetic parameters in the red-eared slider (Trachemys scripta elegans).

The premise that drugs not be injected into the caudal body of reptiles because they will be carried by the renal portal system to the kidneys, where they may be nephrotoxic or rapidly excreted, was tested by comparing the pharmacokinetics of gentamicin (excreted via glomerular filtration in mammals) and carbenicillin (excreted partly via renal tubular secretion in mammals) following injection into the forelimb or hindlimb of red-eared sliders (Trachemys scripta elegans). Ten sliders received intramuscular gentamicin (10 mg/kg) in a forelimb (n = 5) or a hindlimb (n = 5), and plasma levels of the drug were assayed over time. Following drug clearance, the experiment was repeated with the site of injection reversed so that each animal acted as its own control. Another 10 sliders were similarly treated, using intramuscular carbenicillin (200 mg/kg). Injection site of gentamicin had no effect on any pharmacokinetic parameter (time to maximum plasma concentration, maximum plasma concentration, half-life, area under the curve, clearance, and volume of distribution). However, the area under the curve of plasma carbenicillin concentration vs. time was significantly lower following hindlimb injection, in comparison with forelimb injection, at 1, 4, and 8 hr, which may reflect reduced bioavailability of the drug, as would be expected with renal portal perfusion and tubular excretion on first pass through the kidney. This effect on carbenicillin likely is not clinically important because plasma levels remained above recommended minimum inhibitory concentrations. Because blood draining the caudal body of reptiles passes through the kidneys or the liver before reaching the central circulation, the effect on the pharmacokinetics of a drug injected in that region will vary with its renal or hepatic extraction rate. Generally, this effect is unlikely to be significant.

Amikacina en dosis única diaria en niños neutropénicos con fiebre / Amikacin once-daily in febrile neutropenic children

Se realizó un ensayo clínico aleatorizado en niños con cáncer, fiebre y neutropenia para evaluar la eficacia de la amikacina en dosis única diaria contra tres dosis al día asociada a carbenicilina en ambos grupos. Se incluyeron 50 pacientes, 25 pacientes en el grupo A que recibieron la dosis diaria única de amikacina, y 25 pacientes en el grupo B que recibieron la amikacina fraccionada en tres dosis cada 8 horas. No hubo diferencias intergrupos: la fiebre remitió en una mediana de 6 días (2-8días) vs 7 días (3-12 días) en los grupos A y B, respectivamente (p= 0.37); la mejoría clínica se observo en una mediana de 6 días (3-10 días) vs 7 días (2-14 días) (p=0.68). Un paciente en el grupo A y dos en el B fallecieron. Los picos máximos de amikacina al 7o. día de tratamiento fueron de 10-60 y de 7-25 µg/mL en los grupos A y B respectivamente, y los niveles séricos de creatinina de 0.3-0.7 mg/dL para el grupo A y de 0.2 - 0.8 mg-dL para el grupo B; ningún paciente presentó elevación de la creatinina mayor al 40 por ciento del basal. Tres pacientes del grupo A tuvieron niveles de amikacina mayores a 40 µg/mL sin que existiera elevación de la creatinina. No encontramos datos que sugieran que la toxicidad fue mayor. La modalidad de administración de aminoglucósido en una dosis al día parece ser igual de efectiva que la convencional

Randomized trial comparing oral ciprofloxacin plus penicillin V with amikacin plus carbenicillin or ceftazidime for empirical treatment of febrile neutropenic cancer patients.

Aminoglycoside-containing combination therapy has been the standard empirical approach for febrile neutropenic cancer patients. With the advent of the broad-spectrum oral fluoroquinolones, it is now possible to evaluate an initial empirical alternative therapy. A prospective randomized study was conducted comparing oral ciprofloxacin plus penicillin V (group A) with amikacin plus carbenicillin or ceftazidime (group B). Main criteria for eligibility were febrile patients with solid tumor or nonlymphoblastic lymphoma, a Zubrod PS equal to 1 or 2, no diarrhea, mucositis, or long-term central venous catheter. A total of 108 consecutive neutropenic febrile episodes were randomized (5 exclusions); 55 episodes were assigned to group A and 48 to group B. Most febrile episodes were of unknown origin. There were 10 microbiologically documented episodes with two cases of bacteremia. Both regimens were well tolerated. Oral regimen was substantially cheaper than parenteral regimen. Treatment success without regimen modification was 94.5% for group A and 93.8% for group B (p = .86; CI -0.08-0.10). Oral therapy with ciprofloxacin and penicillin V is a safe alternative to standard parenteral therapy in this low-risk group of neutropenic patients, with unquestionable cost containment.

Development and validation of an LC method for the quantitation of carbenicillin in human serum.

An LC method for the quantitation of carbenicillin in human serum has been developed and validated. After protein precipitation with acetonitrile and evaporation, the residue was taken up by citric acid at pH 1.9. Carbenicillin and the internal standard (I.S.), piperacillin, were extracted with ethyl acetate, evaporated to dryness and reconstituted with a buffer solution. The separation of carbenicillin,, the I.S., and matrix peaks was achieved on a Microsorb C18, 3 microns column with a mobile phase of acetonitrile-tetrabutylammonium-phosphate buffer (pH* 6.6). The detection was by UV at 208 nm. The run time was 8 min. The established linearity range was 0.25-20 microgram ml-1 (r2 > 0.99) with a limit of quantitation of 0.25 microgram ml-1. Interday precision (RSD) and bias over the entire range were 1.1-6.9% and -1.83 to +2.80%, respectively. The interday precision (RSD) and bias for the QC samples at 0.75, 3.0 and 12 micrograms ml-1 were 5.9-7.9% and -2.80 to +2.30%, respectively. Stabilities of on-system, bench top, freeze-thaw cycles and sample storage were established.

[The use of clindamycin and netilmicin for preventing postoperative wound infection in patients with cancer of the upper respiratory and digestive tracts]. / Primenenie klindamitsina i netilmitsina dlia profilaktiki posleoperatsionnoi ranevoi infektsii u bol'nykh rakom verkhnikh dykhatel'nykh i pishchevaritel'nykh putei.

Clindamycin (2.7 g/day) and netilmicin (5.6 mg/kg) were used for 6-10 days in 27 patients with laryngeal and oral cancer versus beta-lactam antibiotics and aminoglycosides received by 56 matched patients to prevent infection of the operative wound. Suppuration was observed in 11.1 and 41.4% of the patients, respectively (p < 0.05), the temperature rose over 38 degrees C in 22.2% and 42.9% of the patients, respectively (p < 0.05). The regimens showed similar toxicity. The findings proved high efficacy of clindamycin combination with netilmicin in infection prophylaxis in patients operated on for upper respiratory and digestive tract cancer.

Yersinia spp: Estudo das características biológicas das amostras isoladas de queijo tipo Minas Frescal / Yersinia spp: a study of the biological characteristics of strains isolated fromm minas frescal cheese (white cheese)

resumo: foram analisadas 50 amostras de dez diferentes marcas comerciais de queijo tipo "Minas Frescal", comercializados em supermecados do Rio de Janeiro.Foram pesquisados os microrganismos indicadores de contaminaçäo fecal pelo método do número mais provável.Os coliformes totais variaram de 2, 7*10elevado a terceira/g a 2, 4*10elevado a sexta/g e os coliformes fecais de 2*10/g a 2, 1*10elevado a sexta/g.Das amostras examinadas, 80 por cento mostraram precárias condiçöes higiênico-sanitárias, de acordo com os limites estabelecidos pelos padröes do Ministério da Saúde(DNVS).paralelamente, foram pesquisaas Yersinia spp por três diferentes metodologias.o método do pré-enriquecimento a 26ºC/48 horas e posterior tratamento alcalino sequido de semeadura em agar desoxicolato citrato permitiu a identificaçäo de 11 amostras de Y.frederiksenii-0:16a, 16b-Xo.Pelo método do plaqueamento direto, apenas uma amostra de Y.intermedia-NAG-Xo no meio agar por 7 a 21 dias näo permitiu o isolamento de nenhuma amostra.Essas amostras de yersinia spp foram submetidas aos testes de produçäo de enterotoxina termoestável, autoaglutinaçäo, cálcio-dependência, capacidade de ligaçäo ao cristal violeta, atividade de piraminamidase, atividade enzimática extracelular, com objetivo de avaliar o seu comportamento biológico.Todas se comportam negativamente, com exceçäo de uma amostra de Y.frederiksenii que foi protease positiva.Finalmente, o perfil de sensibilidade das Yersinia spp isoladas, mosxtrou uma multiresistência em relaçäo à vários antimicrobianos.Apresentaram uma melhor sensibilidad ao ácido nalidíxico, amicacina, cloranfenicol, gentamicina, norfloxacina, polimixina B e Tobramicina.Todas as amostras de Yersinia spp isoladas no presente estudo tiveram a capacidade de produzir B-lactamase, através do método de Nitrocefin.

Adverse reactions to prolonged treatment with high doses of carbenicillin and ureidopenicillins.

Charts were reviewed for 63 patients whose chronic pseudomonas osteomyelitis was treated with high doses of extended-spectrum penicillins for prolonged periods. The incidence of untoward drug reactions was significantly higher than expected. Carbenicillin evoked adverse reactions in 22.8% of patients. However, most of these reactions were mild, and a change of drug was required in only 5.7% of cases. No adverse drug reactions were observed with cumulative doses of less than 750 g. In contrast to carbenicillin, the ureidopenicillins were associated with adverse reactions in 67.7% of patients; most reactions were moderate to severe in intensity; a cumulative dose of greater than 250 g produced adverse reactions; and discontinuation or change of therapy was required in 51.6% of cases. The main adverse reactions to both carbenicillin and the ureidopenicillins included rash, drug fever, leukopenia, eosinophilia, thrombocytopenia, and hepatic damage.

Ofloxacin in the management of complicated urinary tract infections, including prostatitis.

Studies of ofloxacin pharmacokinetics and pathogen susceptibilities suggested that this new fluoroquinolone might be particularly well suited to the treatment of urinary tract infections and prostatitis. Compared with carbenicillin and trimethoprim/sulfamethoxazole in separate studies of complicated urinary tract infection, ofloxacin achieved a significantly higher rate (p = 0.048) of microbiologic cures and more clinical cures than carbenicillin, while essentially matching the efficacy of the trimethoprim/sulfamethoxazole combination. Most common organisms were Pseudomonas aeruginosa in the first study and Escherichia coli in the second. In preliminary data from the prostatitis study comparing ofloxacin 300 mg given twice daily with carbenicillin 764 mg given every six hours, microbiologic cure rates were 100 percent with both medications. However, clinical cure rates were significantly higher (p = 0.048) with ofloxacin. Throughout these trials, ofloxacin has shown excellent safety and tolerability, with a lower incidence of nausea and diarrhea than with carbenicillin, and less nausea and rash than with trimethoprim/sulfamethoxazole. In all treatment groups, clinically significant laboratory abnormalities were uncommon and unrelated to the medications. Overall, these studies indicate that in complicated urinary tract infection the efficacy of ofloxacin is comparable with that of trimethoprim/sulfamethoxazole and superior to that of carbenicillin. In chronic bacterial prostatitis, results to date suggest that ofloxacin may be more effective clinically and as effective microbiologically as carbenicillin.