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PubMed1986

Aminoglycoside antibiotics in infectious diseases. An overview.

This article presents an overview of the aminoglycoside antibiotics used in clinical practice. Facts concerning the discovery and properties of the aminoglycosides are followed by information about spectrums of activity and mechanisms of action and resistance. Individual compounds are compared and proposals on the possibilities for their clinical use, both as single drugs and in combination with beta-lactam antibiotics, are made. The importance placed on measuring the serum concentrations of aminoglycoside antibiotics should serve as a remainder that this procedure is important, on one hand, to increase clinical efficacy and, on the other, to reduce the side effects of these antibiotics. Finally, the aminoglycosides are compared briefly with other antibacterial compounds, some of which are very new. There is no doubt that in the future the aminoglycosides will continue to occupy an important place in the treatment of severe infections, although newly developed agents appear to be effective complements.

Amikacin↗
PubMed1986

Susceptibility of aerobic gram-negative bacilli to aminoglycosides. Effects of 45 months of amikacin as first-line aminoglycoside therapy.

Amikacin was instituted as the primary empiric aminoglycoside at the San Juan Veterans Administration Medical Center in January 1982; at that time, 16 percent of the strains at the hospital were gentamicin-resistant. A prospective surveillance study was designed to correlate detection of bacterial resistance with aminoglycoside use. In the current report, the baseline period, during which gentamicin was the first-line aminoglycoside, accounting for 61 percent of overall aminoglycoside use, is compared with the period from January 1982 to September 1985, during which the first-line aminoglycoside was amikacin, accounting for 85 percent of overall use. This study is ongoing. During the two periods, the patient population did not differ with regard to aminoglycoside therapy, indications, or overall aminoglycoside use (541 versus 680 patient days per month). Among the gram-negative bacilli isolated, the percent of strains resistant to amikacin was as follows: pre-baseline period/baseline period, 0.8/0.2 percent; amikacin-usage period, 3.6 percent. Resistance to gentamicin and tobramycin during the period of amikacin use decreased from 16 to 11 percent for gentamicin and from 17 to 11 percent for tobramycin. The decrease in resistance of the gram-negative bacilli to gentamicin varied among strains: the resistance of Escherichia coli decreased from 8 to 4 percent; that of Proteus mirabilis, from 12 to 5 percent; that of indole-positive Proteus, from 19 to 12 percent; that of Acinetobacter, from 57 to 23 percent; that of Citrobacter, from 15 to 7 percent; and that of Pseudomonas aeruginosa, from 24 to 16 percent. During the amikacin-usage period, amikacin resistance was unchanged for most strains, with the exception of P. aeruginosa, the resistance of which increased from 4.5 to 7.8 percent. Of the 4,795 strains isolated, 174 were resistant to amikacin; of these, 29 Pseudomonas strains were studied for all mechanisms of resistance. Changes in permeability were exhibited by 11 of the 29 strains; 14 strains exhibited the AAC(6')-I enzyme, 10 strains exhibited the APH(3')-II enzyme, and two strains exhibited ANT(2") in addition to some other unidentified mechanism. Multiple enzyme production was found in 15 of the strains. The use of amikacin as a first-line aminoglycoside is associated with a decrease in resistance to other aminoglycosides and a slight increase in overall resistance to amikacin among aerobic gram-negative bacilli. The usefulness of amikacin has not been affected at our institution.

Acetyltransferases↗
PubMed1986

Risk factors and comparisons of clinical nephrotoxicity of aminoglycosides.

Controversy continues regarding risk factors for nephrotoxicity and the possible differences in nephrotoxicity rates associated with the aminoglycosides commonly used in clinical practice. Review of published data, including 27 comparative clinical studies, indicates the following: sensitive markers of tubular toxicity do not correlate directly with clinically significant diminution in glomerular filtration rate; of all the proposed risk factors, few are consistently found; despite numerous studies, some with potential drawbacks, no current aminoglycoside has been shown to be consistently and conclusively less nephrotoxic than another; and, as per a previous recommendation, the choice of an aminoglycoside should not be made on the basis of nephrologic criteria.

Amikacin↗
PubMed1986

The potential for discovery and development of improved aminoglycosides.

Following the development of amikacin, pharmaceutical companies made intensive efforts to find even more potent and broader-spectrum aminoglycosides. This effort was justifiable in view of the fact that over the preceding decade, these agents, because of their unique properties, had proven to be the primary weapons in the therapeutic armamentarium for the treatment of seriously ill patients. Since the toxicities associated with the aminoglycosides were beginning to limit their use in general medicine, researchers ultimately shifted their emphasis from probing for higher-potency, broader-spectrum agents to finding those with a reduced potential for toxicity. This article addresses the issue of whether superior aminoglycoside derivatives will reach the marketplace in the future. A comparison is made of several key properties of virtually all aminoglycosides that have reached an advanced preclinical development stage, gone into the clinic, or been registered for commercial use over the past 10 years. The following parameters are used for comparisons with already marketed aminoglycosides: antibacterial potency, as measured by relative minimum inhibitory concentrations for 50 percent of the strains tested, against wild-type Pseudomonas aeruginosa; degree of resistance to inactivation by microbial enzymes; and potential for toxicity utilizing comparative acute intravenous lethal doses for 50 percent of the population in mice, values that appear to predict the maximum recommended daily doses in man. An assessment of a number of compounds, including three structurally related to gentamicin, two to sisomicin, two to kanamycin A, three to kanamycin B, and two to fortimicin, revealed that none had overall properties superior to those already being utilized commercially. In no case did a compound prove to be less toxic, and in many instances, the antibacterial potency of the newer agents was lower than that exhibited by the older aminoglycosides. Some increase in resistance to inactivating enzymes was seen, but only BB-K 311 proved refractory to more enzymes than did amikacin. In view of this and the fact that no new agents of promise have moved into the development stage during the past five years, it seems safe to say that the current armamentarium of aminoglycosides is all that will be available for use in the foreseeable future.

Aminoglycosides↗
PubMed1991

The role of laparoscopy in acute pelvic infections.

54 patients presented by history, physical examination and laboratory tests with suspected pelvic inflammatory disease (PID). The use of laparoscopy as a diagnostic tool proved in 13 cases (24%) that the presumptive diagnosis was incorrect. Bacteriological studies revealed chlamydial infection in 21 of 41 cases, in 6 cases only at laparoscopy in the pelvic cavity, gonococcal in 9 of 41 cases; mycoplasmas were identified in 15 cases, being the only pathogen in 7. In 9 cases, no recognized pathogens were isolated. Polymicrobism was frequent. Follow-up studies identified 5 cases of treatment failure; 2 of Gonococcus and 3 of Chlamydia, and detected 3 cases of Chlamydia which had not been identified initially. We discuss the use of laparoscopy in the diagnosis and for follow-up and treatment of PIDs.

Acute Disease↗
PubMed1993

Serial measurements of transient evoked otoacoustic emissions (TEOAEs) in healthy newborns and in newborns with perinatal infection.

Detection of hearing impairment in early childhood is difficult. We serially recorded transient evoked otoacoustic emissions (TEOAEs) to search for signs of ototoxicity in term, healthy newborns and compared the results to a second group of term babies treated for perinatally acquired bacterial infection with ampicillin plus either cefotaxime or plus aminoglycoside. At initial evaluation, in the group of 45 healthy children born at term, well reproducible emissions were observed in all but two children. In each of these two, initially well reproducible TEOAEs were detected in one ear only. At the time of the second recording (mean at day 8.5) excellent emissions were seen in all ears of all children. Similarly, in the second group receiving ampicillin plus either cefotaxime or plus aminoglycoside, the height of emissions as well as TEOAE-reproducibility was equal or even increased at the time of the second evaluation in all 17 patients. In the following group of 59 patients, all receiving ampicillin plus aminoglycoside, again TEOAEs were equal or improved at the time of follow-up examinations. In all patients, a reduced general condition tended to be associated with less reproducible TEOAEs. We conclude that at conventional doses in low-risk infants, aminoglycosides are unlikely to cause ototoxicity and that in early childhood serial TEOAE-recording may be useful for evaluation of inner ear function.

Ampicillin↗
PubMedDate not supplied

Mathematical modelling of bacterial growth at subinhibitory levels of aminoglycosides.

The subinhibitory effect of antibiotics has often been studied without any clear theoretical framework; we have chosen to use mathematical bacterial growth modelling as a useful tool to analyse these biological states in a more rigorous manner. Since their mode of action and molecular target are relatively well known, aminoglycosides were well suited for this more sophisticated study of subinhibitory action. We have shown that two models (the Monod and the logistic models) regularly used in bacteriology, were adequate to describe these effects in a glucose-limited medium. A change of model, according to antibiotic concentration, revealed the existence of two separate actions. At lower concentrations, inhibition affected mainly glucose use, the substrate remained limiting and growth mode did not change. As soon as the concentration exceeded a threshold, growth was totally disturbed, probably through a physiological "catastrophe". This threshold can be used to estimate bacterial susceptibility to these antibiotics.

Aminoglycosides↗
PubMed1991

A randomized comparative study of the prophylactic use of trimethoprim-sulfamethoxazole versus netilmycin-metronidazole in transrectal prostatic biopsy.

An open randomized study was done to compare the prophylactic value of single doses of netilmycin-metronidazole versus trimethoprim-sulfamethoxazole in the prevention of postoperative infections associated with transrectal prostatic biopsy. Of 117 patients enrolled in the study 101 were evaluated and of these patients 47 received netilmycin-metronidazole and 54 received trimethoprim-sulfamethoxazole. The bacteremia rate in the netilmycin-metronidazole group was 28% (13 of 47 patients) with a 95% confidence interval of 18 to 42% and in the trimethoprim-sulfamethoxazole group it was 37% (20 of 54) with a confidence interval of 26 to 50% (p = 0.43). None of the patients with bacteremia was symptomatic. Urinary tract infection rates were greater in the netilmycin-metronidazole group: 17% (8 of 47 patients) versus 2% (1 of 54) in the trimethoprim-sulfamethoxazole group, p = 0.01. Trimethoprim-sulfamethoxazole (cotrimoxazole) is a better choice as an antimicrobial prophylaxis for patients undergoing transrectal prostatic biopsy.

Aged↗
PubMed2001

Neonatal group B streptococcal infection. Results of 33 months of universal maternal screening and antibioprophylaxis.

OBJECTIVE: To assess the efficacy and pitfalls of a protocol of generalized screening for group B Streptococcus (GBS) and intra-partum treatment of all carriers in a clinical setting. DESIGN: A descriptive study and comparison with an historical group. SETTING: A tertiary perinatal center. POPULATION: All women attending prenatal care in our center and delivered after 37 weeks were eligible. Study period ranged from January 1994 to September 1996. Comparison group consisted in deliveries of years 1992 and 1993. METHODS: Vaginal cultures were performed at 36 weeks on non-selective medium followed by intra-partum treatment of all carrier mothers. Rate of carriage, incidence of neonatal GBS sepsis, influence of risk factors and the reasons for failures were analysed. Comparison was made with an historical group. Statistical analysis was performed using a Chi-square test. RESULTS: There were 5374 term deliveries during the study. 3906 were screened (72.7%) and 559 of them found positive for GBS (14.3%). We observed 46 early-onset GBS diseases (0.86% of term-births). 43.5% of infections occurred in babies born from mothers without risks factors at delivery. Negative GBS cultures at sampling accounted for 43.5% of protocol failures. Comparison of the incidence of early-onset GBS disease with the previous two years showed a significant drop (1.45-0.86%, P<0.05). CONCLUSIONS: Our protocol revealed feasible and effective in reducing the incidence of early-onset GBS disease. Improvements must be studied particularly as to the predictive value of screening cultures.

Amoxicillin↗