Limited information indicates that carbenicillin produces low levels in milk that are not expected to cause adverse effects in breastfed infants. Occasionally disruption of the infant's gastrointestinal flora, resulting in diarrhea or thrush have been reported with penicillins, but these effects have not been adequately evaluated. Carbenicillin indanyl disodium is acceptable in nursing mothers.

Three new Lycopodium alkaloids, carinatumins A-C (1-3), have been isolated from the club moss Lycopodium carinatum. Structures and stereochemistry of 1-3 were elucidated on the basis of 2D NMR correlations. Carinatumins A (1) and B (2) exhibited a potent inhibitory activity against acetylcholinesterase.

Transport of carbenicillin (CBPC) and its orally active prodrug (carindacillin, CIPC) was studied with rat intestinal brush border membrane vesicles (BBMV). CIPC was transported uphill into BBMV in the presence of a H(+) gradient, indicating that CIPC absorption is carrier-mediated. Indeed, CIPC was predominantly transported by the monocarboxylic acid transport system, although it might be possible that CIPC possesses some affinity to the oligopeptide transporter. In contrast, CBPC exhibited no affinity to either the oligopeptide or the monocarboxylic acid transport system. Apparent uptake clearance of CIPC was approximately 70-fold greater than that of CBPC. It was clarified that the modification of the chemical structure of CBPC (a dicarboxylic acid) to CIPC (a monocarboxylic acid) by ester formation may have resulted in the increased affinity to the monocarboxylic acid transport system, which, in turn, led to improved absorption of the prodrug.

Absorption characteristics of carindacillin (CIPC) were investigated using Caco-2 cells, and the results were compared with those of its parent drug, carbenicillin (CBPC). Uptake of CBPC was not affected by the metabolic inhibitor or the change in extracellular pH. CBPC appeared to be taken up into Caco-2 cells by passive diffusion. In contrast, the uptake of CIPC was greater at lower extracellular pH and was inhibited in the presence of carbonyl cyanide p-(trifluoromethoxy)phenyl hydrazone, a protonophore. Also, transport of CIPC through Caco-2 cell monolayer was energy and temperature dependent. Moreover, the uptake and transport of CIPC were significantly inhibited in the presence of various monocarboxylic acids, which are the substrates of the monocarboxylic acid transport system(s), whereas the substrates of the oligopeptide transporter had no effect on the uptake or transport of CIPC. These results suggested that the absorption of CIPC may be mediated by the monocarboxylic acid transport system(s), not by the oligopeptide transporter. Furthermore, the uptake and transport of CIPC were approximately 40-fold greater than those of CBPC. Therefore, it is likely that the participation of a carrier-mediated transport in the absorption of CIPC may significantly contribute to the improved absorption of the prodrug over the parent drug.

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.

In a double-blind study, 30 patients having transurethral surgery for bladder tumors were randomly assigned to receive prophylactic carbenicillin indanyl sodium or a placebo perioperatively. Only one patient in the carbenicillin group had a postoperative urinary infection due to carbenicillin-resistant Klebsiella oxytoca organisms. Thus, no advantage from the prophylactic use of antibiotics was evident in this uninfected group of patients.

The pathogenesis, clinical signs and symptoms, diagnosis and treatment of chronic bacterial prostatitis (CBP) are reviewed. The most common organism associated with CBP is Escherichia coli, although infections with Klebsiella, Enterobacter, Proteus, Pseudomonas, and enterococci have also been documented. The only symptoms of CBP may be those of an acute urinary-tract infection. The use of simultaneous quantitative urine cultures represents the most accurate method for diagnosing CBP. The use of trimethoprim-sulfamethoxazole, the current drug of choice for CBP, is based on results in animals showing good penetration of trimethoprim into acidic prostatic fluid and the knowledge that normal human prostatic fluid is acidic. Studies in patients with CBP, who have alkaline prostatic fluid, have demonstrated poor penetration of trimethoprim into prostatic fluid, which may explain the cure rate of about 40% seen with trimethoprim-sulfamethoxazole. A few patients have been treated successfully with kanamycin and streptomycin, but these drugs must be given by injection. Carbenicillin indanyl sodium has been associated with cure rates of almost 70% in a small number of studies. Both doxycycline and minocycline have been used to treat CBP, but inadequate urine-culture data make these studies difficult to evaluate. Erythromycin produced a cure rate of 88% in one study in patients who received 500 mg (as the stearate salt) four times daily for 14 days. Local injection of antibiotics into the prostate has been reported to be effective in a few cases. Although controlled comparative trials with trimethoprim-sulfamethoxazole are needed, carbenicillin indanyl sodium and erythromycin appear to be the drugs of choice for treating CBP; trimethoprim-sulfamethoxazole should be reserved for patients with CBP unable to tolerate or unresponsive to therapy with these agents.

The intestinal absorption of alpha-esters of carbenicillin disodium, carbenicillin phenyl sodium, and carbenicillin indanyl sodium was investigated using the in situ rat intestinal recirculating method. In the in situ intestinal lumen at pH 7, two prodrugs were rapidly converted to poorly absorbable carbenicillin, possibly by the action of intestinal nonspecific esterase in competition with the slow absorption of prodrugs. At pH 5, the reduced action of esterase and the increased absorption rate after 3 hr resulted in 50 and 60% absorption of carbenicillin phenyl sodium and carbenicillin indanyl sodium, respectively. The absorption rate constants determined for both prodrugs were in good agreement with the prediction from the quantitative structure-absorption rate relationship derived from the two-compartment aqueous diffusion model.

Transrectal biopsy is one of the more popular methods for the diagnosis of prostatic cancer. However, there is disagreement as to whether the use of prophylactic antimicrobials decreases the incidence of fever and urinary tract infections, which may follow this procedure. A prospective randomized double-blind study involving 63 patients was instituted to determine the efficacy of carbenicillin indanyl sodium in reducing these complications. The protocol consisted of administration of 2 tablets of 4 times daily of a placebo or the treatment drug 24 hours before and after biopsy. Clean catch urine cultures were obtained 24 hours before biopsy and at 48 hours and 2 weeks after the procedure. Blood cultures were performed 15 minutes after biopsy. In addition, clinical parameters were monitored closely in the hospital for 48 hours after biopsy. A total of 48 patients was considered evaluable. Of 23 patients who received the study drug 2 (8.6 per cent) had positive urine cultures at 48 hours compared to 9 of 25 (36 per cent) from the placebo group. A similar result was observed from the 2-week culture data, in which 2 of 23 patients (8.6 per cent) in the treatment group had positive urine cultures as opposed to 5 of 25 (20 per cent) receiving the placebo. Fever occurred in 48 per cent of the placebo and in 17 per cent of the carbenicillin groups. Our data indicate that prophylactic administration of carbenicillin indanyl sodium decreases the complications of fever and urinary tract infections following transrectal biopsy of the prostate.

The efficacy and safety of carbenicillin indanyl sodium were evaluated in 16 patients with acute or chronic bacterial prostatitis. Each patient received carbenicillin indanyl sodium (Geocillin) tablets, at a dosage of two 500 mg tablets (each tablet equivalent to 382 mg of carbenicillin) four times daily for either 14 days (acute patients) or 28 days (chronic patients). Clinical and bacteriologic success rates, based upon 4 week post therapy followup, were 93 per cent and 75 per cent respectively. There were no adverse reactions. Results with cephalexin in a concurrently treated alternative therapy group were generally unsatisfactory. Further evaluations of carbenicillin indanyl sodium in this treatment of resistant populations are clearly warranted.

Distribution of ampicillin, amoxicillin, bacampicillin, mecillinam, pivmecillinam, carbenicillin, indanyl sodium was studied in the canine prostate, prostatic interstitial fluid, and prostatic secretion. All seven antibiotics were found in higher concentrations in the prostatic interstitial fluid than in the prostatic secretion. As expected for weak acids, drug concentrations in these fluids were always lower than the simultaneous serum concentrations. Tissue penetration was enhanced for the penicillin ester, pivmecillinam, as shown by its prostatic secretion/serum and tissue/serum ratios, which were higher than those of the other antibiotics, including the esters, bacampicillin, and carbenicillin indanyl sodium. This results may be due to pivmecillinam's long hydrolysis half-life. The concentrations for these penicillanic acid derivatives in prostatic interstitial fluid were above the minimal inhibitory concentrations for most of the commonly encountered gram-negative bacteria encountered in prostatitis. Therefore, these antibiotics should be effective in the treatment of bacterial prostatitis caused by susceptible organisms. Carbenicillin and carbenicillin indanyl sodium had the highest prostatic interstitial fluid/serum ratios of the compounds tested, and theoretically, therefore, they should be the most effective in the treatment of prostatitis. However, clinical trials should be carried out to confirm this.