Combined Action of Carbenicillin and Gentamicin on Pseudomonas aeruginosa In Vitro

The minimal inhibitory and minimal bactericidal concentrations of carbenicillin and gentamicin were determined for 10 strains of Pseudomonas aeruginosa isolated from the urinary tract. Combinations of the two drugs were tested for possible enhanced activity. Such enhancement was demonstrated in the inhibitory activity of combinations for eight strains. Striking bactericidal activity against five strains was achieved by the combination, whereas neither drug alone in low dosage was capable of bactericidal action. The possible mode of action and the possible merit of pursuing these preliminary findings are discussed.     

Susceptibility of Pseudomonas aeruginosa to Carbenicillin

Ninety clinical isolates of Pseudomonas aeruginosa were examined for susceptibility to carbenicillin by the broth dilution and disc diffusion methods. Inhibition zone diameters varied at given minimal inhibitory concentration levels of the antibiotic. Nevertheless, the results obtained allowed the proposal of the following tentative criteria for the interpretation of inhibition zones. Pseudomonadaceae yielding zones of inhibition measuring at least 10 and 16 mm in diameter around 25-and 100-mug discs, respectively, are sensitive to this antibiotic when examined by the standardized Bauer-Kirby method of disc susceptibility testing. Isolates characterized by zones of less than 100 mm in diameter around 25-mug discs should be tested with 100-mug discs before they are reported as sensitive or resistant to carbenicillin.     

Susceptibility of Pseudomonas aeruginosa to Carbenicillin

[This corrects the article on p. 630 in vol. 20.].     

In Vitro Effects of Carbenicillin Combined with Gentamicin or Polymyxin B Against Pseudomonas aeruginosa

Disodium carbenicillin and gentamicin sulfate have both shown promise in the treatment of infections caused by Pseudomonas aeruginosa. This study was designed to explore possible synergistic relationships among the new as well as the established antimicrobial agents used to treat such infections. With an agar dilution technique, minimum inhibitory concentrations of 27 strains of P. aeruginosa were determined in two-dimensional tests. Graphs of equal biological activity (isobolograms) demonstrated moderate synergistic effects of the carbenicillin-gentamicin combination over therapeutically feasible concentration ranges. In contrast, the combination of carbenicillin and polymyxin B showed only additive or slightly antagonistic effects. Tests of bacterial killing confirmed the presence of carbenicillin-gentamicin synergy in 3 of 6 strains of P. aeruginosa, but did not show true antagonism between carbenicillin and polymyxin B. Clinical trials of both drug combinations are advisable to determine whether therapeutic results can be improved, and whether the dosages of gentamicin or polymyxin B can thereby be reduced to lessen their toxic hazards.     

Susceptibility of Pseudomonas aeruginosa to Gentamicin Sulfate In Vitro: Lack of Correlation Between Disc Diffusion and Broth Dilution Sensitivity Data

Seventy-eight of 420 clinical isolates of Pseudomonas aeruginosa yielded zones of inhibition of less than 12 mm in diameter around 10-mug discs of gentamicin sulfate when tested by the standardized Bauer-Kirby disc diffusion method. Of 153 strains chosen from these isolates, one strain (0.65%) required 25 mug of gentamicin per ml for inhibition; the remainder (99.35%) were inhibited by 6 mug/ml or less of the antibiotic. It is recommended that those isolates of P. aeruginosa that yield zones of inhibition less than 12 mm in diameter be disc susceptibility-tested once more; those isolates that give zones of inhibition of less than 12 mm upon repeated examination should then be subjected to the broth dilution test before they are designated as sensitive or resistant to gentamicin.     

Influence of Serum and Calcium on the Bactericidal Activity of Gentamicin and Carbenicillin on Pseudomonas aeruginosa

Because calcium was found to be antagonistic in vitro to the activity of colistin and polymyxin B on Pseudomonas aeruginosa, the effects of calcium and serum on gentamicin and carbenicillin were also examined. Serum was antagonistic to gentamicin in antibiotic tube dilution tests on five strains of P. aeruginosa. Serum was not antagonistic to carbenicillin in tube dilution tests. Physiologic concentrations of calcium antagonized the activity of gentamicin but not carbenicillin. The antagonism observed with gentamicin was less than that previously seen with colistin. The antagonistic effect of calcium and serum was removed by a chelating agent. Gentamicin and carbenicillin may be more active in vivo against P. aeruginosa than colistin or polymyxin B.     

Effect of Carbenicillin on Pseudomonas aeruginosa

The activity of carbenicillin against 200 strains of Pseudomonas aeruginosa was measured by a quantitative agar dilution method. Minimal inhibitory concentrations (M.I.C.''s) for five graded inocula were measured in terms of complete inhibition (CI) and reduced growth (RG). The M.I.C. decreased progressively as inocula were reduced, median values for the 200 strains ranging from 100 to 37.5 μg. per ml. by the CI criterion, and from 75 to 25 μg. per ml. by the RG definition. Ratios of M.I.C. obtained for large and small inocula were usually small. Identical M.I.C.''s by both CI and RG criteria were most often obtained when the inoculum for the RG criterion was 1 or 2 logs higher than that for complete inhibition.Population analysis of 15 strains of Ps. aeruginosa showed that one specific drug concentration usually caused a sharp drop in proportion of viable cells, ranging from 3 to 5 logs. None of the populations were completely non-viable even at 150 μg. per ml. There was evidence that the viability of different-sized populations was reduced disproportionately by carbenicillin.Carbenicillin 300 μg. per ml. exerted appreciable bactericidal effect against nine of 15 strains of Ps. aeruginosa after a 24-hour contact period; after only six hours the bactericidal effect was very small.Quantitative sensitivity measurements for carbenicillin should include M.I.C. values for both CI and RG criteria, using a range of inocula for testing. Such M.I.C. values may well be useful in monitoring carbenicillin therapy of tissue infections.     

In Vitro Susceptibility of Strains of Pseudomonas pseudomallei to Rifampin

Reported high activity of rifampin for Pseudomonas pseudomallei could not be verified by extensive in vitro tests conducted with 31 recently isolated strains. Minimal inhibitory concentrations of rifampin were 25 μg/ml for three strains and greater than 25 μg/ml for 28 strains. Rifampin had relatively poor in vitro activity when compared with tetracycline drugs and chloramphenicol antibiotics now commonly used for treating melioidosis.     

Susceptibility In Vitro and In Vivo of Pseudomonas pseudomallei to Rifampin and Tetracyclines

Tests were performed on 64 strains of Pseudomonas pseudomallei to compare rifampin, various tetracyclines, and other antibiotics for inhibitory activity in vitro. Rifampin minimum inhibitory concentration (MIC) values generally fell between 25 to 50 μg/ml. For deoxycycline, methacycline, tetracycline, and minocycline, MIC means ranged from 1.3 to 2.7 μg/ml. Delayed treatment tests in subacute mouse infections revealed a better rifampin activity than was expected from its weak activity in vitro, whereas of the others, minocycline appeared superior. None of these five antibiotics demonstrated fully curative effectiveness in terms of mouse survival or eradication of residual infection in organs.     

Induction of Spheroplasts of Pseudomonas aeruginosa by Carbenicillin

Speroplasts of Pseudomonas aeruginosa were induced with carbenicillin. Morphological changes were observed as early as 1.5 hr after the initial exposure to carbenicillin.     

Carbenicillin Resistance in Pseudomonas aeruginosa from Clinical Material

Strains of Pseudomonas aeruginosa resistant to 256 μg. per ml. or more of carbenicillin (Pyopen) were isolated from 17 patients over a period of three months. The infections were not solely due to cross-infection. Low dosage and attempted eradication of the organism from inaccessible sites, such as the bronchi or skin surfaces, by using systemic treatment are two possible causes. Restraint in treating infections of doubtful importance and the use of local applications to appropriate sites with or without systemic treatment is suggested.     

Carbenicillin and gentamicin in the treatment of Pseudomonas aeruginosa infection

The administration separately and sequentially of carbenicillin and gentamicin eradicated Ps. aeruginosa infections, during the period over which they were given, in all of 25 critically ill patients. Electron microscopy revealed differences in the action of these two antibiotics against Ps. aeruginosa in vitro. Culture studies showed synergism between them and destruction by gentamicin of the carbenicillin-induced long, filamentous form of the organism.     

Pseudomonas aeruginosa Inhibits the Growth of Scedosporium and Lomentospora In Vitro

Mycopathologia - In vitro bacterial–fungal interaction studies in cystic fibrosis (CF) have mainly focused on interactions between bacteria and Candida. Here we investigated the effect of...     

Inhibition of Macrophage Phagocytosis by Pseudomonas aeruginosa Rhamnolipids In Vitro and In Vivo

Patients with cystic fibrosis often have chronic and ultimately lethal pulmonary infections with Pseudomonas aeruginosa. In order to understand why these bacteria resist pulmonary clearance, we have investigated the interaction of P. aeruginosa and phagocytic cells. In an earlier study we reported that sub-lytic concentrations of two glycolipids produced by P. aeruginosa (the mono- and dirhamnolipids) caused structural changes in human monocyte-derived macrophages, and at lower concentrations inhibited the phagocytosis of Staphylococcus epidermidis by these cells. In the present study we demonstrate that rhamnolipids also inhibit the in vitro phagocytosis of both P. aeruginosa and Saccharomyces cerevisiae by thioglycollate-elicited mouse peritoneal macrophages. Using lucifer yellow to label the lysosomal compartments of macrophages, we determined that rhamnolipids interfere with the internalization of attached particles and reduce the level of phagosome-lysosome fusion of internalized targets within macrophages. We also demonstrate that physiologically relevant concentrations of rhamnolipids injected intratracheally into rat lungs inhibited the response of alveolar macrophages to a challenge of zymosan particles in vivo. These studies further demonstrate the profound inhibitory effects of P. aeruginosa rhamnolipids on macrophage function and are consistent with our hypothesis that the in situ production of these rhamnolipids directly contributes to the persistence of this pathogen in cystic fibrosis patient lungs. Received: 15 December 1995 / Accepted: 22 January 1996     

In Vitro Activity of Carbenicillin Against Gram-negative Bacilli

The activity of a new semisynthetic penicillin, carbenicillin, was determined against 241 strains of gram-negative bacilli with the tube-dilution technique. Of 143 strains of Pseudomonas sp., 99 had a minimal inhibitory concentration of 200 to 300 mug/ml. The majority of strains of Escherichia coli and Proteus spp. were sensitive to this antibiotic, with minimal inhibitory concentrations of 25 mug/ml or less. Strains of Klebsiella sp. were quite resistant to carbenicillin. The size of inoculum had no significant effect on the minimal inhibitory concentration for Pseudomonas sp.     

In Vitro Synergistic Activities of Essential Oils and Surfactants in Combination with Cosmetic Preservatives Against Pseudomonas aeruginosa and Staphylococcus aureus

The aim of this study is to evaluate possible synergistic antimicrobial interactions between common cosmetic preservatives and selected essential oils or surfactants. The antimicrobial efficacy of six essential oils, three surfactants and five preservatives against Pseudomonas aeruginosa ATCC 9027 and Staphylococcus aureus ATCC 43387 was assessed by a broth micro-dilution assay. MICs for individual and combined antimicrobials were determined and then transformed to fractional inhibitory concentration (FIC) indexes. All essential oils exhibited antibacterial activity; among surfactants, bacteria resulted most susceptible to the cationic agent. Synergy was observed when essential oils of eucalyptus and mint were combined with methylparaben against P. aeruginosa, while essential oils of mint, oregano and sage combined with propylparaben and imidazolidinyl urea acted against S. aureus. Many binary mixtures of preservatives and surfactants produced synergistic activity with the most effective interactions involving the cationic and amphoteric compounds under study. FIC indexes demonstrated synergistic effects when preservatives were combined with either essential oils or surfactants against both bacterial strains. These results highlight the potential usefulness of essential oils and surfactants to enhance the activities of conventional biocides. This kind of study should contribute to the selection and optimization of preservative systems for cosmetic preparations.     

Susceptibility of Recent Isolates of Pseudomonas aeruginosa to Gentamicin, Polymyxin, and Five Penicillins, with Observations on the Pyocin and Immunotypes of the Strains

The susceptibilities of recently isolated strains of Pseudomonas aeruginosa to gentamicin, polymyxin B, carbenicillin, ampicillin, penicillin G, and two newer penicillins were tested with the inocula-replicating technique by using undiluted and 10(-3) dilutions of the cultures. With either inoculum, polymyxin B was the most active agent, and a comparison with previous data from this laboratory showed that the susceptibility of P. aeruginosa to this antibiotic had not changed over the past 20 years. Gentamicin was nearly as active as polymyxin, all but 2 of the 141 strains tested with the diluted inoculum being inhibited by 6.25 mug/ml or less. AB-2288, an agent resembling carbenicillin, was four times more active than carbenicillin or BLP-1654; the last two were equally active against the 10(-3) inoculum. A more marked inoculum effect was noted with the penicillin analogues tested, the increase in minimum inhibiting concentration with the undiluted culture being eight-fold for carbenicillin and at least 16-fold for AB-2288 and BLP-1654. Pyocin typing and serotyping failed to demonstrate any clearly predominating types.     

In Vitro Susceptibility of Selected Bacteria to Cefaclor

Cefaclor is an orally absorbed cephalosporin antibiotic chemically and pharmacologically similar to cephalexin. It appears to be more active than cephalexin against susceptible strains. The in vitro sensitivity of 230 clinical bacterial isolates to cefaclor was studied. Most isolates of S. aureus, K. pneumoniae, E. coli, and indole negative Proteus species were inhibited at clinically attainable serum and urine concentrations. Like cephalexin, cefaclor was less active against isolates of Enterobacter species, indole positive Proteus species and enterococci although many of these isolates were inhibited at concentrations achievable in urine.