Aminoglycosides In Treatment Research Articles

Prospective evaluation of single-dose aminoglycosides for treatment of complicated cystitis in the emergency department.

Antimicrobial resistance among Enterobacterales continues to be a growing problem, particularly in those with urinary infections. Previous studies have demonstrated safety and efficacy with the use of single-dose aminoglycosides in uncomplicated cystitis. However, data in complicated infections are limited. Single-dose aminoglycosides may provide a convenient alternative for those with or at risk for resistant pathogens causing complicated urinary infections, especially when oral options are unavailable due to resistance, allergy, intolerance, or interactions with other medications. This study evaluated the safety and effectiveness of single-dose aminoglycosides in treatment of complicated cystitis in the emergency department (ED). This was a multicenter, prospective study performed between July 2022 and March 2023 of patients who met criteria for complicated cystitis and were otherwise stable for discharge at an academic ED. Primary outcomes were clinical or microbiologic failure within 14 days of treatment. Safety was assessed by review of adverse events. Descriptive statistics were used. Thirteen patients were included. Complicating factors were male sex (n = 4), kidney stone (n = 2), urinary catheter (n = 6), recent urologic procedure (n = 1), urinary hardware (n = 1), antibiotic allergy precluding use of alternate oral options (n = 4), immunocompromised status (n = 2), and <1-year history of multidrug-resistant organisms on urine culture (n = 8). Eleven patients (85%) had positive urine cultures in the preceding 12 months with no oral antimicrobial option. Eight patients (62%) received amikacin (median dose 15 mg/kg), four patients (31%) received gentamicin (median dose 5 mg/kg), and one patient (8%) received tobramycin (5 mg/kg) for treatment. Ten patients (77%) reported resolved urinary symptoms after treatment and 11 patients (85%) reported no new urinary symptoms since discharge. No patient required hospital admission for treatment failure, and no adverse events were noted. Single-dose aminoglycosides appear to be a reasonably effective and safe treatment for complicated cystitis, which avoided hospital admission in this cohort.

Adjunctive inhaled amikacin in infants with Ventilator-Associated Pneumonia optimizes the complex antimicrobial therapy: pilot study.

VAP remains the second leading cause of death among the patients with nosocomial infections and its incidence varies significantly from 5% to 60% reaching on average 10 %. It is of crucial importance to develop novel treatment approaches and optimize the existing ones. Thus, the aim of this pilot study was to study the laboratory-microbiological effect of inhaled aminoglycosides in a complex treatment of patients with ventilator-associatedpneumonia(VAP). Methods: To study the laboratory-microbiological effect of adjunctive inhaled aminoglycosides in the treatment of VAP, twenty enrolled patients were randomly subdivided into 2 groups (n=10). Amikacin was administered via a nebulizer starting from the first day of VAP manifestation. Inhalations were performed BID for 7 days via a nebulizer integrated into the breathing circuit. We assessed: cell membrane alterations in leukocytes, Annexin V/7-AAD staining for leukocytes, ROS detection assay for leukocytes. Adjunctive administration of inhaled amikacin reduced the fluorescence intensity ratio more efficiently compared with the intravenous antimicrobial treatment with no aerosolized amikacin following both 48 h and 96 h of treatment. The amount of dead necrotic annexin V-negative, 7-AAD-positive leukocytes was significantly lower under the use of inhaled amikacin than at the beginning of treatment. Conclusions In this pilot study, we found that administration of aerosolized amikacin combined with the systemic antimicrobial therapy improves the clinical outcome of patients with VAP, effective early microbial decrease in the sputum, reduces reactive oxygen species generation in leukocytes and the degree of leukocyte apoptosis and necrosis, decreases VAP-mediated cell membrane alterations of circulating leukocytes.

Reduced Chance of Hearing Loss Associated with Therapeutic Drug Monitoring of Aminoglycosides in the Treatment of Multidrug-Resistant Tuberculosis.

Hearing loss and nephrotoxicity are associated with prolonged treatment duration and higher dosage of amikacin and kanamycin. In our tuberculosis center, we used therapeutic drug monitoring (TDM) targeting preset pharmacokinetic/pharmacodynamic (PK/PD) surrogate endpoints in an attempt to maintain efficacy while preventing (oto)toxicity. To evaluate this strategy, we retrospectively evaluated medical charts of tuberculosis (TB) patients treated with amikacin or kanamycin in the period from 2000 to 2012. Patients with culture-confirmed multiresistant or extensively drug-resistant tuberculosis (MDR/XDR-TB) receiving amikacin or kanamycin as part of their TB treatment for at least 3 days were eligible for inclusion in this retrospective study. Clinical data, including maximum concentration (Cmax), Cmin, and audiometry data, were extracted from the patients' medical charts. A total of 80 patients met the inclusion criteria. The mean weighted Cmax/MIC ratios obtained from 57 patients were 31.2 for amikacin and 12.3 for kanamycin. The extent of hearing loss was limited and correlated with the cumulative drug dose per kg of body weight during daily administration. At follow-up, 35 (67.3%) of all patients had successful outcome; there were no relapses. At a median dose of 6.5 mg/kg, a correlation was found between the dose per kg of body weight during daily dosing and the extent of hearing loss in dB at 8,000 Hz. These findings suggest that the efficacy at this lower dosage is maintained with limited toxicity. A randomized controlled trial should provide final proof of the safety and efficacy of TDM-guided use of aminoglycosides in MDR-TB treatment.

Comparison of ß-lactam plus aminoglycoside versus ß-lactam plus fluoroquinolone empirical therapy in serious nosocomial infections due to Gram-negative bacilli

We sought to compare clinical cure on day 7 and a 28-day all-cause mortality in patients who received an anti-pseudomonal ß-lactam with a fluoroquinolone or an aminoglycoside for treatment of nosocomial bacteremia or pneumonia due to Gram-negative bacilli while in the ICU. This retrospective cohort study was conducted in critically ill patients at an academic medical centre from January 2005 to August 2011. A total of 129 patients (83 receiving aminoglycoside and 46 receiving fluoroquinolone combinations) were included. Seven-day clinical cure rates were 74% and 72% for fluoroquinolone and aminoglycoside groups, respectively (p = 0.84). There was no significant difference in the odds of clinical cure with a fluoroquinolone as compared to an aminoglycoside combination (adjusted odds ratio 2.4, 95% confidence interval [CI] 0.7–9.0). There was no significant difference in 28-day mortality in patients who received a fluoroquinolone or an aminoglycoside combination (22% vs. 18%, adjusted hazard ratio 0.82, 95% CI 0.29–2.28).

English

Enterococcal UTI is a well-known source of fatal bacteraemia & endocarditis. OBJECTIVE: Identification of different species of Enterococci causing nosocomial urinary tract infection in a tertiary care hospital along with antibiotic susceptibility pattern. METHODS: Admitted patients developing symptoms of UTI atleast after 48 hours of admission were included in this study over a period from January-June 2013.Urine samples collected in appropriate sterile manner were screened for pus cells and bacteria followed by speciation according to Facklam-Collins scheme. Enterococcal isolates were preserved in CTA until tested by VITEK2 (bioMerieux) with AES to confirm the speciation. Antibiogram was performed by disk diffusion method (modified Kirby -Bauer technique) on Muller-Hinton agar and blood agar media. MIC of the tested antibiotics was detected by VITEK 2 with AES which provides accurate fingerprint recognition of bacterial resistance. RESULTS: Out of total 187 urine samples, 34 were culture positive (18%) of which Enterococci were isolated in 9 cases (26.4%); E nterococ cus f aec alis & Enteroc occ us f aec ium four each along with one E nteroc occ us gallinarum strain. Isolated E nterococc us gallinarum and all isolated E nterococc us f aec alis were sensitive to Penicillin group of drugs, although all isolated Enterococcus faecium were resistant to them. None of the Enterococcal isolates produced β- lactamase. In isolated Enterococcus gallinarum and one Enterococcus faecalis isolate, MIC value of Ampicillin was double that of Benzyl-penicillin. Isolated Enterococcus gallinarum was the only Vancomycin resistant Enterococcus strain. According to VITEK2 AEC, it was of vanA type with MIC ≥32μg/ml. All four Enterococcus faecalis isolates were resistant to Quinupristin & Dalfopristin whereas isolated Enterococcus faecium were sensitive to those antimicrobials. All of the isolates were sensitive to Nitrofurantoin except one Enterococcus faecium isolate (MIC value 64μg/ml) and Enterococcus gallinarum isolate (MIC value 64μg/ml), both of which were intermediately susceptible to the drug. CONCLUSION: Four E nterococ cal isolates were susceptible to Ampicillin and Aminoglycosides (high level synergy) suggesting use of combination therapy of Ampicillin and Aminoglycosides for treatment. Vancomycin and Linezolid are the only available drugs for treatment of isolates resistant to both or any one of the drugs Ampicillin and Aminoglycosides (high level synergy). To treat VRE, Linezolid may be prescribed.

A study of oxidative stress in gentamicin induced nephrotoxicity and effect of antioxidant vitamin C in Wistar rats.

Background: Gentamicin is very useful aminoglycoside in treatment of gram negative organisms but nephrotoxicity has been a major limiting factor. Various renal pathologies have shown correlation with generation of oxidative stress. So, it was hypothesized that there may be involvement of oxidative stress in gentamicin nephrotoxicity. Aims & Objective: To investigate the role of oxidative stress in gentamicin-induced nephrotoxicity and its prevention by using antioxidant vitamin C in Wistar albino rats. Another objective was to localize the site of kidney damage produced by gentamicin. Materials and Methods: Male Wistar albino rats were administered gentamicin at the dose of 70 mg/kg/day i.m; either alone or in combination with vitamin C. Parameters of oxidative stress like glutathione peroxidase (GPx), glutathione reductase (GR) and total antioxidant status (TAS) were analysed. Renal damage was measured by blood urea and serum creatinine. Histopathological examination of rat kidney was done. The data was subjected to one way ANOVA with post hoc test of significance and the values of P < 0.05 were considered statistically significant. Results: Treatment with gentamicin caused significant reduction of TAS, GPx and GR activity, while blood urea and serum creatinine level were raised significantly as compared to control. Renal damage was confirmed with histopathological studies. The primary site of damage was identified as tubules especially proximal convoluted tubules. Administration of vitamin C alone raised TAS level significantly. Co-administration of vitamin C along with gentamicin led to significant restoration of GPx, GR, TAS, blood urea and serum creatinine level. Conclusion: Renal damage due to gentamicin is associated with oxidative stress. The primary site of damage was renal proximal convoluted tubules. Co-administration of vitamin C along with gentamicin significantly prevented nephrotoxicity by virtue of its antioxidant effect.

Use of aminoglycosides in treatment of infections due to intracellular bacteria.

Soon after antibiotics were introduced into medical practice, authors pointed out that microorganisms capable of surviving within phagocytic cells may be protected from the killing actions of antibiotics with a poor ability to cross the eukaryotic cell membrane, leading to therapy failures and disease relapses (86, 108). Following the pioneering work by Bonventre et al. (21) that showed that mouse peritoneal macrophages were impermeable to streptomycin in vitro, the aminoglycosides have been included in such a category. Failure of streptomycin and other aminoglycosides to treat infections due to strict or facultative intracellular pathogens (e.g., rickettsial diseases, chlamydial diseases, and typhoid fever) have reinforced this point of view. Also, in vitro infected cell systems have been developed to test the activities of antibiotics against intracellular pathogens, and in many instances they have shown the limited intracellular activity of aminoglycosides compared to their strong bactericidal potential in extracellular medium (52, 92). However, at the same time, streptomycin was successfully used to treat infections due to facultative intracellular pathogens, such as tuberculosis (especially tuberculous meningitis) (120), plague (133), brucellosis (160), or tularemia (55). As for tuberculosis, clinical data were concordant with the demonstration by Mackaness et al. (106) that streptomycin could inhibit growth of Mycobacterium tuberculosis within macrophages. Both these clinical and experimental data have been overlooked for several decades. Later experiments by Tulkens et al. (22, 179) have confirmed that aminoglycosides are readily incorporated into phagocytes when these cells are in contact with the antibiotic for prolonged periods (i.e., more than 24 h). The present review deals with the potential role of aminoglycosides, and especially streptomycin, in the antibiotic therapy of infections due to intracellular pathogens. Our goal is to highlight the concept that categorization of aminoglycosides as strictly ineffective against intracellular pathogens is in some ways too simplistic and does not correspond to clinical experience, since aminoglycosides remain in fact a “gold standard” therapy in a number of infections due to intracellularly surviving pathogens.

Current therapy of urinary tract infections and pyelonephritis.

U RINARY tract infections (UTIs) are common problems in both inpatient and outpatient settings. Despite the frequency with which these infections are encountered and the volume of literature concerning them, controversy still exists about their optimal treatment. Recent studies have helped to delineate the etiologies of acute dysuria in women, one of the most common presentations of UTIs, and have begun to compare different regimens of treatment. It is now apparent that Stuphylococcus saprophyticus is a common cause of UTIs in young women. Nosocomial UTIs remain a major cause of morbidity and mortality despite vigorous attempts to prevent them. New antimicrobial agents are available for treatment of UTIs; some may eventually replace nephrotoxic aminoglycosides for treatment of severe or complicated infections. Diagnostic tests and antimicrobits are not inexpensive; in these days of cost containment, the clinician is challenged by the need to find the most cost-effective means to treat and prevent UTIs. The goals of treatment of UTIs are to provide relief of symptoms, eradicate the focus of infection, prevent recurrences due to either relapse of the same infection or acquisition of a new infection, and to prevent renal damage. Unless obstruction of urine flow caused by anatomic variant, stone, or other problem is present, UT1 in adults rarely causes renal parenchymal damage sufficient to lead to end-stage renal disease. Success in treatment of UT1 correlates best with the susceptibility of the causative microorganism to concentrations of antimicrobics, which can be attained in urine rather than the concentration attainable in blood. In theory, use of bacteriocidal drugs would be preferable, but there is no real evidence that bacteriocidal drugs are superior to bacteriostatic agents. Because response to therapy is dependent on a number of factors including the site of infection, presence of complicating factors such as neurogenie bladder, stones, or need for indwelling catheters, there is no single best treatment plan. Rather, the costs, side effects, inconvenience to the patient, and the likelihood that a particular treatment will be effective must be evaluated for each patient. This article discusses some of the recent developments in the understanding and therapy of the major categories of UTIs that occur in adults: acute dysuria of women, pyelonephritis, prostatitis, and asymptomatic bacteriuria in special situations. For more comprehensive reviews of UTIs, the reader is referred to several recent publications.’ 4