MIC Values In Range Research Articles

Essential Oil Composition and Antimicrobial Activity of Wild and Cultivated Moroccan Achillea ageratum L.: a Rare and Threatened Medicinal Species

The essential oils of leaves and flowers of the wild and cultivated Moroccan Achillea ageratum L., a rare and threatened medicinal species, were examined by GC/MS, and their chemical compositions were compared. At least nine components were identified in both wild and cultivated A. ageratum oils, representing more than 95% of the oils. Artemisyl acetate (62.34-78.79%), yomogi alcohol (4.89-12.40%), santolina alcohol (4.86-11.77%), and artemisia alcohol (3.36-7.04%) were the major compounds. Terpene-alcohol proportion was higher in wild A. ageratum than in cultivated A. ageratum. The antibacterial analysis showed that both oils presented high activity against all the studied Gram-positive strains in a range of MIC values from 2.55 to 7.02 mg/ml, but they appeared not effective against the tested Gram-negative ones (MIC values 20.40-41.10 mg/ml). They also exhibited remarkable antifungal activities against Candida species with MIC values ranging from 5.83 to 8.42 mg/ml. From these results, it was concluded that domestication of this threatened medicinal species using clonal propagation did not significantly affect its chemical composition and consequently its antimicrobial properties.

Ertapenem Pharmacokinetics and Pharmacodynamics during Continuous Ambulatory Peritoneal Dialysis

Scant data exist for the pharmacokinetics (PK) of ertapenem in patients on continuous ambulatory peritoneal dialysis (CAPD). The goals of this study were to characterize the PK profile of ertapenem during CAPD, determine the extent of ertapenem penetration into the peritoneal cavity, and quantify the probability of the target attainment (PTA) profile in the serum and peritoneal cavity. A single-dose PK study was conducted in seven patients on CAPD. Population PK modeling and Monte Carlo simulation determined the probability that ertapenem at 500 mg intravenously (i.v.) every 24 h (q24h) would achieve concentrations in excess of the MIC for 40% of the dosing interval (40% T>MIC, where T is time) in the serum and peritoneal cavity. Monte Carlo simulation was also used to calculate the peritoneal cavity/serum mean and median penetration ratios by estimating the area under the concentration-time curve in the peritoneal cavity and serum (AUC(Peritoneal) and AUC(Serum), respectively) from zero to infinity after a single simulated dose. The population mean (± standard deviation [SD]) values for the apparent volume in the central compartment, clearance, and apparent volume in the peritoneal cavity were 2.78 (0.62) liters, 0.24 (0.07) liters/hr, and 5.81 (2.05) liters, respectively. The mean (SD) AUC(Peritoneal)/AUC(Serum) ratio was 1.039 (0.861), and the median penetration ratio was 0.801 (interquartile range, 0.486 to 1.317). In both the serum and peritoneal cavity, ertapenem at 500 mg i.v. q24h was very likely (>90%) to achieve the pharmacodynamic target for MICs of ≤2 mg/liter. The simulations suggest that 500 mg of ertapenem i.v. q24h is very likely to achieve the exposure target associated with clinical efficacy in both the serum and peritoneal cavity against the range of MIC values deemed susceptible by the Clinical and Laboratory Standards Institute.

Population Pharmacokinetics of Fluconazole in Critically Ill Patients Receiving Continuous Venovenous Hemodiafiltration: Using Monte Carlo Simulations To Predict Doses for Specified Pharmacodynamic Targets

Fluconazole is a widely used antifungal agent that is extensively reabsorbed in patients with normal renal function. However, its reabsorption can be compromised in patients with acute kidney injury, thereby leading to altered fluconazole clearance and total systemic exposure. Here, we explore the pharmacokinetics of fluconazole in 10 critically ill anuric patients receiving continuous venovenous hemodiafiltration (CVVHDF). We performed Monte Carlo simulations to optimize dosing to appropriate pharmacodynamic endpoints for this population. Pharmacokinetic profiles of initial and steady-state doses of 200 mg intravenous fluconazole twice daily were obtained from plasma and CVVHDF effluent. Nonlinear mixed-effects modeling (NONMEM) was used for data analysis and to perform Monte Carlo simulations. For each dosing regimen, the free drug area under the concentration-time curve (fAUC)/MIC ratio was calculated. The percentage of patients achieving an AUC/MIC ratio greater than 25 was then compared for a range of MIC values. A two-compartment model adequately described the disposition of fluconazole in plasma. The estimate for total fluconazole clearance was 2.67 liters/h and was notably 2.3 times faster than previously reported in healthy volunteers. Of this, fluconazole clearance by the CVVHDF route (CL(CVVHDF)) represented 62% of its total systemic clearance. Furthermore, the predicted efficiency of CL(CVVHDF) decreased to 36.8% when filters were in use >48 h. Monte Carlo simulations demonstrated that a dose of 400 mg twice daily maximizes empirical treatment against fungal organisms with MIC up to 16 mg/liter. This is the first study we are aware of that uses Monte Carlo simulations to inform dosing requirements in patients where tubular reabsorption of fluconazole is probably nonexistent.

Comparison of drug sensitivity and genotypes of clinically isolated strains of levofloxacin-resistant Streptococcus pneumoniae obtained from Okinawa Island, the Japanese main island and Hong Kong

The prevalence of fluoroquinolone-resistant Streptococcus pneumoniae is increasing worldwide. In the present study, a comparison of drug sensitivity and genotypes of clinically isolated strains of levofloxacin (LVFX)-resistant S. pneumoniae obtained from Hong Kong, Okinawa Island and the Japanese main island (Honshu) was performed. MICs of quinolones (LVFX, tosufloxacin, ciprofloxacin, gatifloxacin and sitafloxacin (STFX)) and other antibiotics (penicillin G, cefcapene, cefditoren, clarithromycin and azithromycin) were determined by a microdilution broth method according to the Clinical and Laboratory Standards Institute Standards. The quinolone-resistance determining regions (QRDRs) of gyrA, gyrB, parC and parE of these strains were analyzed by PCR-based sequencing. All 40 strains tested had more than one amino-acid substitution in the QRDRs of gyrA, gyrB, parC or parE. Although there seemed to be some clonality in strains obtained from Hong Kong, there was no clonality in strains obtained from Okinawa and Japan. Strains obtained from Hong Kong, Okinawa Island and the Japanese main island were genetically different by pulsed-field gel electrophoresis analysis. The range of MIC values of STFX against isolates resistant to LVFX (MIC 4-32 mg l(-1)) was 0.12-0.5 mg l(-1), and MIC(80) values of STFX against LVFX-resistant isolates were 0.25 mg l(-1). This study suggests that LVFX-resistant S. pneumoniae is similar in all three locations and STFX is potent against LVFX-resistant S. pneumoniae with multiple mutations in QRDRs of gyrase A and topoisomerase IV.

Pharmacokinetics of florfenicol after intravenous and intramuscular administration in New Zealand White rabbits

The pharmacokinetic disposition and bioavailability of florfenicol (FF) were determined after single intravenous (i.v.) and intramuscular (i.m.) administrations of 25 mg/kg b.w. to ten healthy New Zealand White rabbits. Plasma FF concentrations were determined by high-performance liquid chromatography (HPLC). The plasma pharmacokinetic values for FF were best described by a one-compartment open model. The elimination half-life ( t 1/2β) was different ( p < 0.05) however, the area under curve (AUC) was similar ( p > 0.05) after i.v. and i.m. administrations. FF was rapidly eliminated ( t 1/2β 1.49 ± 0.23 h), slowly absorbed and high ( F, 88.75 ± 0.22%) after i.m. injection. In addition, FF was widely distributed to the body tissues ( V ss 0.98 ± 0.05 L/kg) after i.v. injection. In this study the time that plasma concentration exceeded the concentration of 2 μg/mL was approximately 6 h. For bacteria with MIC of 2 μg/mL, frequent administration at this dose would be needed to maintain the concentration above the MIC. However, it is possible that rabbit pathogens may have MIC values less than 2 μg/mL which would allow for less frequent administration. Further studies are necessary to identify the range of MIC values for rabbit pathogens and to identify the most appropriate PK-PD parameter needed to predict an effective dose.

First detection of plasmid-mediated, quinolone resistance determinants qnrA, qnrB, qnrS and aac(6')-Ib-cr in extended-spectrum -lactamase (ESBL)-producing Enterobacteriaceae in Budapest, Hungary

Sir, Quinolone resistance in Enterobacteriaceae usually results from mutations in genes coding for chromosomally encoded type II topoisomerases, efflux pumps or porin-related proteins. Recently, transferable, plasmid-borne, quinolone resistance genes—qnrA, qnrB, qnrS, cr variant of aac(60)-Ib, qepA and oxqB—have been observed in clinical isolates, more frequently among strains producing plasmid-mediated, extended-spectrum b-lactamases (ESBLs). The objective of this study was to determine the prevalence of qnrA, qnrB, qnrS and aac(60)-Ib-cr genes in ESBL-producing clinical isolates of 70 Escherichia coli, 101 Klebsiella pneumoniae, 5 Citrobacter freundii and 61 Enterobacter spp., isolated in two microbiological laboratories in Budapest by collecting samples from seven different hospitals and clinics from 2002 until 2006. The prevalence of ESBL production among Enterobacteriaceae was between 1% and 28% during this period. All of the ESBL-producing organisms were tested for the presence of qnrA, qnrB, qnrS and aac(60)-Ib genes by PCR. To distinguish the qnr gene alleles, restriction enzymes were used and the result was further confirmed by sequencing. The aac(60)-Ib-cr was identified by digestion with BstF5I. The prevalence of qnr determinants was relatively high among K. pneumoniae (8%) isolates and low in the case of E. coli (1.4%) and in Enterobacter spp. (0%). One ESBL-producing C. freundii isolate (out of five) was qnr-positive. qnrA1, qnrB2 and qnrS1 were detected and qnrA1 was the most prevalent (3%) (Table 1). Sixty-three (26.6%) of all ESBL-producing isolates were positive for aac(60)-Ib, of which 19 (8% of all)—16 K. pneumoniae and 3 E. coli—had the aac(60)-Ib-cr variant. None of the qnr-positive strains harboured the aac(60)-Ib-cr variant. The MICs of quinolones were determined by a broth microdilution method according to the CLSI. Conjugation assays were performed for all of the qnr-positive isolates. The qnrA1-positive strains—six K. pneumoniae and one E. coli— were resistant to nalidixic acid, norfloxacin, ciprofloxacin and levofloxacin with very high MIC values (Table 1). The conjugation assay, which was successful in three qnrA1-positive strains, confirmed that the presence of qnrA1 gene alone causes only low-level quinolone resistance. The MIC values for the transconjugants were more than 8-fold higher for nalidixic acid, 132-fold higher for norfloxacin and 66to 132-fold higher for ciprofloxacin, compared with E. coli J53 Rif (nalidixic acid, 4 mg/L; norfloxacin, 0.06 mg/L; and ciprofloxacin, 0.12 mg/L). However, the transconjugants still showed only low-level quinolone resistance, suggesting that the high-level quinolone resistance in the original isolates may be related to the coordinating action of several resistance mechanisms. The qnrB gene was detected in two isolates: one K. pneumoniae and one C. freundii. K. pneumoniae M95 harboured both qnrA1 and qnrB2 genes, but only qnrA1 was transferable by conjugation, suggesting that the two genes have different genetic backgrounds. The ciprofloxacin and levofloxacin MIC values were the highest in K. pneumoniae M95, compared with the other qnrA1-positive strains, which might be explained by the parallel qnrA1 and qnrB2 production of the original isolate. The transfer of qnrA1 alone did not result in transconjugants with greatly altered quinolone susceptibility. The C. freundii M141 harbouring only the qnrB2 gene was susceptible to the fluoroquinolones tested with MICs at least 8-fold lower than the susceptibility breakpoints recommended by the CLSI. Other authors have also observed that QnrB is present in isolates with a wide range of quinolone MIC values, including full susceptibility. The wide range of MIC values for the qnr-positive strains highlights that the detection of the qnr genes in clinical strains might be very difficult phenotypically. The qnrS1 gene was detected only in a K. pneumoniae strain, which was resistant to most of the tested fluoroquinolones. However, the norfloxacin (16 mg/L) and ciprofloxacin (4 mg/L) MIC values were the breakpoints recommended by the CLSI. The levofloxacin MIC value (4 mg/L) was between the two CLSI breakpoints (8 and 2 mg/L). Of the 19 aac(60)-Ib-cr-positive isolates, 6 (32%) were susceptible to both ciprofloxacin and levofloxacin. The presence of aac(60)-Ib-cr does not result in large increases in MIC values of quinolones; however, it substantially increases the frequency of selection of chromosomal mutants. The characteristics of the b-lactamase enzymes—isoelectric points, PCR and sequencing data—produced by the qnr-positive strains were determined. In our study, the presence of qnrA1 gene was connected to SHV-5, SHV-12 and CTX-M-15 enzymes (Table 1). The presence of qnrB2 was connected with SHV-12. We could not determine the genotype of the ESBL enzyme in the qnrB2-positive C. freundii strain. The qnrS1 gene was found together with SHV-2 ESBL. Journal of Antimicrobial Chemotherapy doi:10.1093/jac/dkn206

Ten-Membered Lactones from Phomopsis sp., an Endophytic Fungus of Azadirachta indica

Four new 10-membered lactones ( 1- 4) and one known one ( 5) were isolated from the broth extract of an endophytic fungus, Phomopsis sp., obtained from the stem of Azadirachta indica. Their structures were assigned by analysis of spectroscopic data, and the structures of 1 and 4 were also confirmed by X-ray analysis. Compounds 1- 5 were tested for antifungal activity against several plant pathogens. Compound 4 demonstrated antifungal activity in the MIC value range 31.25-500 microg/mL.

Living with ESBLs

Living with ESBLs

Synergistic effect of polyethylenimine plus piperacillin/tazobactam on clinicalPseudomonas aeruginosa isolates resistant to piperacillin/tazobactam

We investigated thein vitro susceptibility of piperacillin/tazobactam in association with polyethylenimine (PEI), a synthetic polycation polymer, against 24 clinical isolates ofPsedomonas aeruginosa resistant to piperacillin/tazobactam. The strains were isolated from patients with respiratory tract infections. MIC of piperacillin/tazobactam was determined by agar dilution method in accordance with NCCLS methodology. An inoculum of 104 CFU/spot with or without PEI (250 nM final concentration) was used. Killing curves were performed for 3 piperacillin/tazobactam resistant strains chosen for their different range of MIC values to piperacillin/tazobactam (128, 256 and 512 mg/L, respectively). Analyses were performed in duplicate using a concentration of antibiotic of 16 mg/L. The addition of PEI (250 nM) increased the susceptibility of piperacillin/tazobactam (from 8 to 32 folds) in all the strains tested. Moreover, in all the strains tested piperacillin/tazobactam in association with PEI showed a bactericidal activity before 6 h. Intrinsic resistance ofP. aeruginosa affects susceptibility to penicillins and is believed to entail broad spectrum impermeability. Different theories suggest that some degree of structure or organization exists in the periplasm ofP. aeruginosa and that this modulates both the level of intrinsic, impermeability-determined resistance expressed by a strain and the efficiency with which the β-lactamase can contact and destroy the incoming β-lactamase molecules. The explanation of this behaviour could be that PEI determines an increased permeability of the outer membrane ofP. aeruginosa; tazobactam inhibits β-lactamase allowing the antibacterial activity of piperacillin. In conclusion our data suggest that PEI can be expected to act as a vehicle for experimental drug delivery into cells, and as a potentiating agent for antibacterial agents that are normally excluded by Gram-negative bacteria.

Bioactive Oligostilbenoids from the Stem Bark of Hopea exalata

Hopeanolin (1), an unusual resveratral trimer with an ortho-quinone nucleus, was isolated and characterized from the stem bark of Hopea exalata. Also obtained were six known stibenoids, shoreaphenol (2), vaticanol G (3), alpha-viniferin (4), pauciflorol A (5), vaticanol A (6), and trans-3,5,4'-trihydroxystilbene 2-C-glucoside (7). The structure of 1 was determined by spectroscopic data interpretation. Compounds 1-7 were tested for antifungal activity and inhibitory effects against jack bean urease. Hopeanolin (1) demonstrated antifungal activity in the MIC value range 0.1-22.5 microg/mL.

Comparative Pharmacokinetic and Pharmacodynamic Profile of Piperacillin/Tazobactam 3.375G Q4H and 4.5G Q6H

When piperacillin/tazobactam has been used to treat hospitalized patients with serious infections, including nosocomial pneumonia caused by Pseudomonas aeruginosa, it has usually been dosed at 3.375 g q4h to provide serum concentrations above commonly encountered organisms’ MICs (T > MIC) for at least 40–50% of the dosing interval. Pharmacodynamic principles suggest that a similar efficacy can be realized with extended dosing intervals when a larger dose (e.g. 4.5 g q6h) is administered, which was the objective of this study. Twelve healthy volunteers, 29.4 ± 8.9 years of age, were enrolled in this multiple-dose, open-labeled, randomized, two-period crossover study. Blood samples were collected after the third dose and concentrations of piperacillin/tazobactam were determined with a validated HPLC method. Pharmacokinetic profiles were determined by noncompartment analysis. T > MIC of piperacillin was calculated for a range of MIC values. Piperacillin/tazobactam was well tolerated in 11 subjects who completed both regimens. The C_max, T_1/2, K, and AUC of P were significantly different according to a paired t test (p < 0.05) between two study regimens. Significant differences (p < 0.05) in tazobactam regimens were noted for C_max, and AUC. The piperacillin/tazobactam regimen of 4.5 g q6h achieved a 44% T > MIC for MIC values of ≤16 µg/ml, while the 3.375-gram q4h regimen achieved 42% T > MIC, for MIC values of ≤32 µg/ml. Dosage regimens for treating serious infections can be extended safely and effectively to 4.5 g q6h and obtain at least 40–50% T > MIC in the coverage of pathogens implicated with serious infections, including P. aeruginosa.

In vitro activity of 11 antimicrobial agents, including gatifloxacin and GAR936, tested against clinical isolates of Mycobacterium marinum

In vitro activities of 11 antimicrobial agents were determined using Etest (AB BIODISK, Solna, Sweden) against 37 clinical isolates of Mycobacterium marinum. The most potent agent (MIC 50, 0.047 μg/mL) was trimethoprim/sulfamethoxazole, but only 91.9% would be categorized as susceptible. Several agents had a complete spectrum of activity including gatifloxacin (MIC 90, 0.38 μg/mL), minocycline (MIC 90, 2 μg/mL), tetracycline (MIC 90, 2 μg/mL) and amikacin (MIC 90, 3 μg/mL). The new glycylcycline, GAR936, had a similar potency (MIC 90, 3 μg/mL) to that of the parent minocycline compound (MIC 90, 2 μg/mL), but the range of MIC values extended to 24 μg/mL. Numerous options appear to exist for the contemporary therapy of M. marinum infections including some newer fluoroquinolones and derivatives of tetracycline (doxycycline, minocycline, GAR936).

Pharmacodynamic interactions of antibiotics alone and in combination.

Clinical trials show that the area under the inhibitory curve (AUIC) is predictive of antibacterial killing rates in patients with nosocomial pneumonia and is useful for predicting clinical or microbiological outcomes and making dosage adjustments with beta-lactams, quinolones, aminoglycosides, and vancomycin. The AUIC values of two antibiotics are additive, and since antibiotics are often given in combination, determining the AUIC for antibiotic combinations could potentially predict the microbiological outcomes for patients given these combinations. To further address this question, mathematical modeling was used to study in vitro pharmacokinetic and pharmacodynamic interactions of the antimicrobials piperacillin and ciprofloxacin. These agents were also studied in vivo in healthy volunteers. Blood samples were obtained for analysis of serum drug concentrations, and serum inhibitory titers were determined against eight common bacterial pathogens, chosen to reflect the range of MIC values to ciprofloxacin and piperacillin. Additive AUIC relationships predictive of bacterial killing rates were typical in patients given these antibiotics in combination.

Evaluation of the Etest for detection of tetracycline resistance in Mycoplasma hominis

The Etest was compared with microbroth dilution for performing in vitro susceptibility tests in 38 isolates of Mycoplasma hominis chosen to represent a wide range of MIC values. MIC 50s were 4 μg/ml for both methods; whereas, MIC 90s were 64 and >256 μg/ml for broth and Etest, respectively. Etest MICs determined on SP 4 agar were usually two or more dilutions greater than microbroth MICs in SP 4 broth, and values were prone to change by one to two dilutions when different inoculum densities were used. Inocula of 10 5 to 10 6 color-changing units/ml gave the most consistently readable MICs, with discrete colony formation surrounding the ellipse. Etest MICs for 5 isolates tested a second time at the same inoculum on SP 4 agar agreed with the original value within 1 dilution. For 12 isolates tested on A 8 agar simultaneously with SP 4 agar, MICs for 10/12 agreed within one dilution; whereas, in the other 2 isolates, MICs varied by two dilutions. These findings suggest that the Etest, when properly controlled, can be used to determine tetracycline MICs for M. hominis.

Antifungal Spectrum and Fungicidal Mechanism of an N-Terminal Peptide of Bovine Lactoferrin

The antifungal spectrum and fungicidal mechanism of an N-terminal peptide of bovine lactoferrin (lactoferricin B), an antimicrobial peptide produced by gastric pepsin digestion of bovine lactoferrin, were investigated. The susceptibility of pathogenic yeasts and dermatophytes to the peptide varied in a species-dependent and strain-dependent manner. Dematiaceous fungi and dimorphic fungi were susceptible to the peptide (range of MIC values: 0.63 to 10μg/mL). In the case of nonpigmented hyphomycetes and zygomycetes, most strains exhibited resistance to the peptide (MIC:>80XYSμg/ mL). This peptide killed Candida albicans dose dependently without inducing a change in cell wall stability against osmotic stress. The peptide at 10μg/ml immediately induced the release of K+ from C. albicans cells and pH increases in cell suspensions. These pharmacological activities were more potent than those for miconazole nitrate, a well-known antifungal agent that interferes with membrane synthesis and function. These in vitro findings suggest that the lactoferrin oligopeptide has potent membrane disrupting activity against this yeast and suggests that in vivo LF-B studies would be useful to further understand host defenses and to develop improved therapeutic agents against yeast infections.

Patent Evaluation: Substituted Cephalosporins as Antibacterial Agents

SummaryNovelty: 3-Arylpropenyl substituted cephalosporin derivatives are disclosed. They are potentially useful antibacterial agents.Biology: Minimum inhibitory concentrations of the compounds are presented against a variety of organisms including penicillin and cephalothin resistant strains. MIC values range from 0.1–10.0 μg/ml for selected compounds against sensitive and resistant strains of Straphylococcus aureus and Klebsiella pneumoniae. Selected compounds were also shown to be effective in vivo against S. aureus, E. coli and P. aeruginosa with PD50 values of between 0.3–0.6 mg/kg imChemistry: Preparation of the compounds is outlined in two synthetic schemes and exemplified in fifty cases which form a subsidiary part of the claim. A biologically active compound is 7-[(Z)-2-(2-aminothiazol-4-yl)-2-(1-carboxy-1-methylethoxyimino)acetamido]-3-[(E)-3-(5,6-dihydroxy-2-methyl-2-isoindolino)-1-propen-1-yl]-3-cephem-4-carboxylate.Structure:

The spectrum of antibiotic resistance in human and veterinary isolates of Escherichia coli collected from 1984-86 in northern India.

This study was undertaken to assess the spectrum of drug resistance prevalent in Escherichia coli isolates from human and animal populations in Northern India. Three hundred and two isolates of Escherichia coli isolated from various infections of humans (47 from diarrhoea; 101 from urinary tract infection) and veterinary animals (17 from poultry septicaemia; 75 from bovine diarrhoea; 14 from ovine diarrhoea and 48 from equine metritis) were studied for their susceptibility to ampicillin, cephaloridine, amoxycillin, cloxacillin, oxytetracycline, doxycycline, chloramphenicol, gentamicin, and trimethoprim-sulphamethoxazole. 63.2% of the isolates (37.7%, human; 25.5%, animal) were resistant to one or more drugs, of which about 41% isolates were multiresistant. Resistant isolates had a wide range of MIC values from 12 to 3200 mg/L, irrespective of origin. Most of the isolates (43.5%) were resistant to ampicillin (MIC greater than 16 mg/L) followed by oxytetracycline (MIC greater than 5 mg/L) (36.4%). Only 9.3% isolates were resistant to trimethoprim-sulphamethoxazole (MIC greater than 21 mg/L). The E. coli isolated from animals tended to be resistant to fewer antibiotics than those isolated from man. 99% of the isolates from human urinary tract infection were resistant compared to only 48.9% of the isolates from diarrhoea. Most of the resistant isolates from animals were recovered from diarrhoea, followed by septicaemia and metritis. This study shows that a high frequency of multiresistant strains are prevalent in both human and animal bacterial populations of Northern India. Since the exchange of these strains among both populations is possible, they pose a great risk in both the selection and the spread of resistance.

Ceftazidime in the treatment of chronic suppurative otitis media in children.

Seventeen children aged 5 months to 3 years with recurrent or chronic otitis media complicated by Pseudomonas aeruginosa were treated with ceftazidime. All patients had been previously treated with several antibiotics. All strains of Pseudomonas were initially sensitive to ceftazidime. In four of the six cases which failed bacteriologically, the Pseudomonas was found to be of intermediate sensitivity after treatment. In 11 patients the Pseudomonas was eradicated during treatment but reappeared in 4 during the follow-up period. All 11 patients were clinically cured or improved. Three of the six children whose Pseudomonas was not eliminated from aural discharge showed some clinical improvement whereas the remaining three showed no clinical response to treatment. The range of MIC values of ceftazidime, gentamicin and carbenicillin for the Pseudomonas isolated were respectively 0.5 to 4.0, 0.25 to 2.0 and 4.0 to 125 mg/l. The mean ceftazidime serum level at 1 h after the first injection of 50 mg/kg was 74.12 (S.D. 12.84) mg/l and at 12 h post injection 1.93 (S.D. 4.14) mg/l.