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.

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.

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.

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.

Combination of amikacin and carbenicillin with or without cefazolin as empirical treatment of febrile neutropenic patients. The International Antimicrobial Therapy Project Group of the European Organization for Research and Treatment of Cancer.

A total of 841 febrile neutropenic patients from 20 centers were randomized to receive carbenicillin (or ticarcillin) plus amikacin or these antibiotics plus cefazolin to compare outcome and incidence of nephrotoxicity. Infection with Escherichia coli, Klebsiella species, Pseudomonas aeruginosa, or Staphylococcus aureus accounted for most of the microbiologically documented febrile episodes. The response to therapy was similar in the two treatment groups for all infections and for bacteremia. Improvement occurred in 35 (64%) of 55 bacteremic patients treated with two antibiotics and 39 (65%) of 60 treated with three antibiotics. An increase in serum creatinine to 2 mg/dL over baseline occurred in eight (2.1%) of 381 patients in the former and in 50 (2.4%) of 364 patients in the latter group. Thus, the two antibiotic regimens were equal in efficacy and in nephrotoxicity. Although not the primary focus of this study, a significant decrease in incidence of infection, including bacteremias, was found in neutropenic patients treated with any oral intestine decontamination regimen.

Piperacillin and gentamicin v carbenicillin and gentamicin for treatment of serious gram-negative infections.

Piperacillin sodium, a new penicillin with remarkable in vitro activity against Pseudomonas aeruginosa and other Gram-negative bacilli, and gentamicin sulfate were compared with carbenicillin disodium and gentamicin in a prospective, randomized, double-blind comparison for treating serious Gram-negative infections. Of the 32 patients whose courses were "evaluable" for efficacy, 12 of 14 who received piperacillin and gentamicin and 13 of 18 who received carbenicillin and gentamicin had favorable outcomes. Of the 99 patients whose courses were evaluable for toxicity, nine of 51 recipients of piperacillin and gentamicin and 15 of 48 recipients of carbenicillin and gentamicin suffered clinical reactions possibly, probably, or definitely related to the penicillin. No statistically significant differences were found in the two groups in the frequencies of biochemical abnormalities, including hypokalemia, that occurred in 19 or 44 recipients of piperacillin and gentamicin and 16 of 45 recipients of carbenicillin and gentamicin. Thus, this study did not prove differences in efficacy of toxicity for piperacillin and gentamicin plus carbenicillin and gentamicin for serious Gram-negative infections.

Piperacillin plus amikacin therapy v carbenicillin plus amikacin therapy in febrile, granulocytopenic patients.

In a prospective randomized trial, febrile, granulocytopenic patients received either piperacillin sodium plus amikacin sulfate or carbenicillin disodium plus amikacin as initial empiric antimicrobial therapy. Although significantly more gram-negative aerobic bacilli isolated from initial cultures were susceptible to piperacillin than to carbenicillin (54 of 58 v 30 of 58), the overall response rates for the two regimens were similar (113 of 143 or 79% for piperacillin plus amikacin and 116 of 154 or 75% for carbenicillin plus amikacin). Piperacillin plus amikacin was associated with less hypokalemia (26 of 143 v 56 of 154). Nephrotoxicity, which was minimal with both regimens, developed less frequently in patients receiving carbenicillin plus amikacin (12 of 143 v two of 154). These results suggest that the overall efficacy of piperacillin plus amikacin is similar to carbenicillin plus amikacin and that piperacillin plus amikacin may be associated with less hypokalemia but more nephrotoxicity.

In vivo inactivation of gentamicin by carbenicillin and ticarcillin.

Inactivation of aminoglycosides by carbenicillin and ticarcillin is a well-recognized in vitro phenomenon. Isolated case reports of in vivo inactivation of gentamicin by either carbenicillin or ticarcillin exist. We report a case of nearly complete in vivo inactivation of gentamicin by both ticarcillin and carbenicillin in the same patient. In the absence of either of the penicillin derivatives, the patient demonstrated predictable plasma concentrations and elimination characteristics of both gentamicin and tobramycin. As in previous reports, the interaction was intensified by high-dose carbenicillin-ticarcillin therapy in the face of underlying renal impairment. When using ticarcillin or carbenicillin along with gentamicin in renally impaired patients, special attention must be paid to both the gentamicin and carbenicillin-ticarcillin doses used and the plasma concentrations obtained.

Kinetics of mezlocillin and carbenicillin.

The kinetics of mezlocillin, a semisynthetic acylureido penicillin, more active than carbenicillin against many gram-negative bacteria, were compared with those of carbenicillin. Following an intravenous infusion of 4 gm in 5 min to 8 normal men there was an average serum level of 294 microgram/ml for mezlocillin and 365 microgram/ml for carbenicillin. The t1/2 for mezlocillin was 47 min and that for carbencillin was 70 min. The apparent volume of distribution was 13.4 L for mezlocillin and 14.4 L for carbenicillin. The mean urinary recovery of mezlocillin was 72% and that for carbenicillin was 92%. Constant infusion of 5 mg of mezlocillin over 2 hr gave steady-state levels of 234 microgram/ml. Half-life, apparent volume of distribution, and serum and renal clearance of mezlocillin after constant infusion were in the same range as those after rapid infusion.

Carbenicillin therapy in patients with normal and impaired renal function.

Optimun therapy with carbenicillin entails the use of high serum concentrations and the risk of significant dose-related toxicity. We report a study of serum clearance method of dose adjustment of carbenicillin patients with normal and imparied renal function. This method was found to provide serum concentrations considered to be satisfactory in every instance, by either constant-rate or intermittent infusion, and should enable greater precision in the use of the antibiotic. Implications of these findings aimed at providing dosage schedules for patients with renal failure are discussed.

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.

Carbenicillin-trimethoprim/sulfamethoxazole versus carbenicillin-gentamicin as empiric therapy of infection in granulocytopenic patients. A prospective, randomized, double-blind study.

The results of therapy with carbenicillin plus trimethoprim-sulfamethoxazole (C-T/S) were compared to those obtained with carbenicillin plus gentamicin (C-G) in a prospective double-blind study of empiric antibiotic therapy in granulocytopenic patients. Patients were stratified into two groups: favorable-prognosis, group 1 (carcinoma, lymphoma, multiple myeloma), or unfavorable-prognosis, group 2 (acute leukemia, bone marrow transplantation), based on anticipated duration of granulocytopenia. Over-all, empiric antibiotic trials were more often successful (P = 0.004) in group 1 (55 of 62 patients or 89 per cent) than in group 2 (42 of 64 patients, 66 per cent)mwithin group 1, there was a favorable outcome in 30 of 32 (94 per cent) C-T/S trials and in 25 of 30 (83 per cent) C-G trials (P = 0.25); within group 2, there was a favorable outcome in 23 of 30 (77 per cent) C-T/S trials and in 19 of 34 (56 per cent) C-G trials (P = 0.14), Combined results in both groups indicated a higher proportion of favorable outcome in C-T/S trials (53 of 62, 85 per cent) than in C-G trials (44 of 64, 69 per cent). Further analysis (Manetl-Naenszel test) showed the over-all difference in outcome to be significant (P = 0.049), but the general applicability of this result may be limited by the rather low incidence of gram-negative bacterial infections in this study. There was no difference between the treatment regimens in antibiotic toxicity, and serious superinfection occurred only in group 2 patients (21 per cent of trials), equally divided between treatment arms. Initial protocol dosing achieved target plasma levels of trimethoprim (3 to 8 micrograms/ml) or gentamicin (4 to 10 micrograms/ml) in 57 of 68 (84 per cent) C-T/S trials compared to 21 of 60 (35 per cent) C-G trials.

Amdinocillin: use alone or in combination with cefoxitin or carbenicillin-ticarcillin.

One hundred fifty-five patients with 157 febrile episodes were treated with amdinocillin or amdinocillin and cefoxitin as second-line therapy, or amdinocillin and ticarcillin or carbenicillin as initial therapy in three separate studies. Overall responses were 57 percent, 55 percent, and 54 percent for amdinocillin, amdinocillin-cefoxitin, and amdinocillin-ticarcillin or amdinocillin-carbenicillin, respectively. In all three studies, patients with septicemia responded less often than patients with other infections. Most patients were profoundly neutropenic at the initiation of therapy, and both the initial neutrophil level and neutrophil trend during therapy influenced response. A significant number of superinfections occurred when amdinocillin alone was used. Although amdinocillin, alone or in combination with cefoxitin, appeared effective as second-line therapy in infections with organisms shown sensitive in vitro, the combination of amdinocillin and ticarcillin or carbenicillin was only moderately effective in initial therapy for neutropenic, febrile, cancer patients.

Granulocytopenia in hospitalized patients. II. A prospective comparison of two antibiotic regimens in the empiric therapy of febrile patients.

The results of empiric antibiotic therapy in 126 hospitalized patients with fever during 192 episodes of granulocytopenia were studied. Febrile granulocytopenic patients were randomly allocated to receive either carbenicillin, methicillin and gentamicin, or carbenicillin and cephalothin. The response rate for the two antibiotic regimens was similar, 49 (60 per cent) of 81 responded to the former and 42 (54 per cent) of 78 to the latter. The response rate in patients receiving other antibiotics because of specific indications or counterindications was 19 (58 per cent) of 33. Thirty-nine (35 per cent) of 110 patients who responded to initial antibiotic therapy had an increase in circulating granulocytes of one log10 or more compared to only 10 (12 per cent) of 79 nonresponders with such an increase. The mortality rate in adult patients receiving carbenicillin, methicillin and gentamicin was eight (16 per cent) of 51, compared to 18 (37 per cent) of 49 in those receiving cephalothin and carbenicillin (P less than 0.05). The significance of this difference in the initial response rate or mortality rate between patients treated with the two antibiotic regimens when only patients with documented bacterial infection were considered. Patients who responded to their initial antibiotic regimen, and patients for whose fever no explanation was found, had the best prognosis.

Bacteriologic cure of experimental Pseudomonas keratitis.

Two long-term therapy trials with high concentrations of antibiotic were carried out to determine the duration of therapy required to achieve bacteriologic cure of experimental Pseudomonas keratitis in guinea pigs. In the first study, corneas still contained Pseudomonas after 4 days of continual topical therapy with either tobramycin 400 mg/ml, amikacin 250 mg/ml, ticarcillin 400 mg/ml, or carbenicillin 400 mg/ml. In an 11-day trial of topical therapy with tobramycin 20 mg/ml, 34 of 36 corneas grew no Pseudomonas after 6 or more days of therapy. The bacteriologic response to therapy in this model occurred in two phases. About 99.9% or more of the organisms in the cornea were killed in the first 24 hr of therapy. The numbers of bacteria remaining in the cornea declined gradually over the next several days until the corneas were sterile. Optimal antibiotic therapy may include two stages: initial intensive therapy with high concentrations of antibiotic applied frequently to achieve a large rapid decrease in numbers of organisms in the cornea, followed by prolonged, less intensive therapy to eradicate organisms and prevent relapse.

The penicillins.

The penicillins as a group are the most frequently and widely used of the antimicrobial agents because they are effective, low in toxicity, and relatively inexpensive. Effectiveness is due to the bactericidal action, the excellent distribution throughout the body spaces, and the wide spectrum of activity. Knowledge of the variation in spectrum of activity of the various types of penicillins is needed for effective use of the appropriate drug against individual infections. Allergenicity is the most frequent and serious problem associated with the use of penicillins. Individual penicillins, however, do have different side effects. The older penicillins are so inexpensive that the cost of their use need hardly be considered, whereas the newer penicillins are expensive and should be used only when they are clearly more effective for treatment than are drugs such as penicillin G.

Endotracheally administered antibiotics for gram-negative bronchopneumonia.

Sisomicin or a placebo was administered endotracheally to two groups of 18 and 20 unconscious patients, respectively, who had tracheostomies or endotracheal tubes in place and developed a severe gram-negative broncho-pneumonia. In addition, the patients received systemically a combination of sisomicin and carbenicillin. A favorable clinical response was obtained in 14 (77 percent) of the 18 patients who were treated with sisomicin and in nine (45 percent) of the 20 patients who received the placebo (P less than 0.05). Endotracheal therapy with sisomicin was well tolerated and resulted in high levels of sisomicin and in elevated bactericidal activity within the bronchial secretions. Endotracheally administered amino-glycosides might be an important adjunct to systemically administered antibiotics in the management of severe gram-negative bronchopneumonia.

Comparative efficacy of ceftazidime vs. carbenicillin and amikacin for treatment of neonatal septicemia.

The efficacy and safety of ceftazidime were compared with those of carbenicillin and amikacin in 60 neonates with proved invasive bacterial infections. The two treatment groups of patients were comparable with regard to sex, gestational and chronologic ages, associated risk factors, clinical condition on enrollment, focus of infection and bacteriology. Escherichia coli was isolated from blood cultures of 31%, Pseudomonas aeruginosa from cultures of 25%, Klebsiella sp. from cultures of 13% and other Gram-negative enteric bacilli from cultures of 17% of the patients. Staphylococcus aureus was isolated from 20% (12 of 60), and coagulase-negative staphylococci from 8% (5 of 60) of the patients. All Gram-negative coliform bacilli were susceptible to ceftazidime whereas 10, 56 and 77% were resistant to amikacin, carbenicillin and ampicillin, respectively. Serum bactericidal activity against the offending pathogen was as much as 5-fold greater in ceftazidime-treated compared with conventionally treated patients. Seven patients with infections caused by organisms resistant to the study drugs were excluded from analysis. Case-fatality rates were 6.4% (2 of 31) and 21% (6 of 28) in the ceftazidime- and amikacin/carbenicillin-treated patients, respectively. Total failure rates, including deaths, were significantly higher in patients treated with amikacin/carbenicillin (8 of 28, 28.5%) compared with that of ceftazidime-treated patients (2 of 31, 6.4%). Thirteen percent (5 of 31) and 3% (1 of 28) of the ceftazidime- and amikacin/carbenicillin-treated patients, respectively, developed invasive Candida albicans superinfection while receiving treatment. In this study results of treatment with ceftazidime were superior to results of treatment with amikacin/carbenicillin for invasive bacterial infections of newborn infants.(ABSTRACT TRUNCATED AT 250 WORDS)

Corticosteroid in experimentally induced Pseudomonas keratitis: failure of prednisolone to impair the efficacy of tobramycin and carbenicillin therapy.

The effect of prednisolone on tobramycin and carbenicillin therapy for experimentally induced Pseudomonas keratitis was evaluated. Results were assessed quantitatively by determining the number of bacteria that survived in the cornea. Simultaneous administration of prednisolone did not adversely alter results of treatment with carbenicillin or tobramycin. In another trial, pretreatment with prednisolone for 48 hours before antibiotic therapy was begun did not change significantly the results of therapy with intramuscular tobramycin or carbenicillin. We conclude that corticosteroid therapy does not affect adversely results of antibiotic therapy with tobramycin or carbenicillin in this experimental model.

Evaluation of the capillary beta-lactamase test and antimicrobial susceptibility of Haemophilus influenzae.

The capillary beta-lactamase test for the detection of Haemophilus influenzae resistance to ampicillin was evaluated against 132 strains of H. influenzae recently isolated from clinical materials and four reference strains. Nineteen strains, including two of serotype b, were beta-lactamase-positive. The minimal inhibitory concentrations (MIC) of ampicillin for the 117 beta-lactamase-negative strains ranged from less than or equal to 0.125 to 2 microgram/ml (only one strain had a MIC of 2 microgram/ml). The range of MIC's of ampicillin was 4 to 64 microgram/ml for the 19 beta-lactamase-positive strains; all but two strains required 8 microgram/ml or more for inhibition. The capillary beta-lactamase test is an easy, rapid and reliable test for the detection of H. influenzae resistance to ampicillin. It is suitable for routine use in the clinical microbiology laboratory. The MIC of carbenicillin was higher for ampicillin-resistant than for ampicillin-susceptible strains, but the highest MIC (32 microgram/ml) was within achievable serum concentrations. Both cefamandole and chloramphenicol were active against all strains.