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PubMed1993

A statistical evaluation of the bactericidal effects of ceftibuten in combination with aminoglycosides and ciprofloxacin.

The bactericidal effects of ceftibuten in combination with netilmicin, isepamicin or ciprofloxacin against two strains of Escherichia coli and three of Klebsiella pneumoniae were studied by the killing curve method. Interpretation of the results was made on a statistical basis by comparing the bactericidal effects observed when the antibiotics were tested alone with those when they were tested in combination. The results were also assessed by survival probabilities according to the ratio of the number of viable bacteria at time t(N(t)) to the initial number of viable bacteria (N(0)). The effects of the combinations were defined in terms of antagonism, indifference, single agonism, addition and synergy by taking account of the confidence intervals of the survival probabilities. All of the combinations exhibited bactericidal activities which were time-dependent. Synergy was demonstrated when ceftibuten was combined with the aminoglycosides, except against the two extended-spectrum beta-lactamase-producing strains of K. pneumoniae, but not when ceftibuten and ciprofloxacin were combined. Antagonism was not demonstrated with any of the combinations.

Aminoglycosides↗
PubMed1994

In-vitro synergy between aminoglycosides deployed against Staphylococcus spp. harbouring a 6'-aminoglycoside acetyltransferase, 2"-aminoglycoside phosphotransferase enzyme.

In-vitro synergistic effects between commercial aminoglycosides are described for gentamicin resistant Staphylococcus strains harbouring 6'-aminoglycoside acetyltransferase activity. Seventy eight strains were studied using the double-disc test and synergy was observed with combinations in which at least one of the components has a garosamine-like 6'-aminosugar. These results were confirmed in chequerboard titrations (sigma FIC < or = 0.5) carried out on Staphylococcus epidermidis strains RYC13036 and RYC4904. Additionally, a clear reduction in tobramycin acetylating activity was observed in the presence of gentamicin or netilmicin in crude extracts of these strains. These experiments suggest that the observed synergy is due to inhibition of the aminoglycoside-modifying enzyme by aminoglycosides with a garosamine like 6'-aminosugar component.

Acetyltransferases↗
PubMed1995

Antistaphylococcal activity of cefdinir, a new oral third-generation cephalosporin, alone and in combination with other antibiotics, at supra- and sub-MIC levels.

Cefdinir is one of the few oral third generation cephalosporins that shows useful activity against nosocomial Gram-positive pathogens. For this reason the anti-staphylococcal potency of the new drug, alone or in combination with other drugs was further characterized. Against penicillin-resistant, oxacillin-susceptible Staphylococcus isolates, cefdinir demonstrated useful in-vitro activity. MIC90 values (in mg/L) were 0.25 for Staphylococcus aureus (30 strains), 0.06 for Staphylococcus epidermidis (24), 0.125 for Staphylococcus hominis (10), 0.5 for both Staphylococcus xylosus (15) and Staphylococcus capitis (11) and 4 for Staphylococcus saprophyticus (10), while Staphylococcus haemolyticus (12) was less susceptible with a MIC90 value of 32. Cefdinir activity was not adversely affected by several variables such as pH, inoculum size or the presence of serum or urine. The new cephem induced a PAE on all isolates studied: with S. aureus the extent of regrowth suppression ranged from 0.8 to 1 h, and with the other species from 0.5 (S. epidermidis) to 4.1 h (S. haemolyticus). Development of resistant strains was rare. At the highest level used (10 x MIC) mutants arose with a frequency of 6 x 10(-8) with S. haemolyticus and 2 x 10(-9) with S. epidermidis. The absence of a paradoxical effect of increasing concentrations of cefdinir on its bactericidal activity was confirmed up to a value of 500-fold the MICs. When cefdinir activity was assessed in association with ciprofloxacin, netilmicin, clarithromycin, fosfomycin, rifampicin, teicoplanin and vancomycin using the chequerboard and time-kill techniques, indifference predominated with all strains and in all combinations. Synergism was detected only in 11 out of a total of 175 tests performed by the chequerboard method. Using the time-kill technique cefdinir reacted synergically in 25 of 126 tests. Antagonism was never observed. S. aureus exposed to sub-inhibitory concentrations of cefdinir failed to grow on mannitol-salt agar and to produce haemolysins, but retained coagulase activity. Penicillinase production was also lost in about 17% of the survivors. Hydrophobicity changes were detected in all species tested with the exception of S. saprophyticus.

Anti-Bacterial Agents↗
PubMed1995

Bactericidal in-vitro activity of beta-lactams and beta-lactamase inhibitors, alone or associated, against clinical strains of Acinetobacter baumannii: effect of combination with aminoglycosides.

Five Acinetobacter baumannii strains of various phenotypes were selected on the basis of the results of a national survey in France in 1991. beta-Lactamases in Acinetobacter isolates were characterized by isoelectrofocusing. We carried out a 24 h time-kill study to assess the bactericidal effect of antibiotic alone or in combination against A. baumannii strains. The initial inoculum was 10(6) cfu/mL. Antibiotics were tested at MIC x 2 when an antibiotic was tested alone and at the MIC for each combination including ticarcillin, piperacillin, ceftazidime or imipenem with or without amikacin or netilmicin and/or beta-lactamase inhibitors. Concentration of inhibitors were: 2 mg/L for clavulanic acid, 4 mg/L for tazobactam and 8 mg/L for sulbactam. Sulbactam and tazobactam showed an intrinsic in-vitro activity against strains susceptible to ticarcillin. A complete killing at 24 h was observed when beta-lactams were combined with amikacin in comparison with antibiotics alone. Synergy was lost when the strain presented a low resistance level to beta-lactams or aminoglycosides except for ticarcillin. Combinations of sulbactam with ticarcillin showed the best bactericidal activity against strains multiresistant to beta-lactams.

Acinetobacter↗
PubMed1996

In-vitro susceptibility of isolates of methicillin-resistant Staphylococcus aureus 1988-1993.

MICs for 423 strains of methicillin-resistant Staphylococcus aureus (MRSA) isolated in Hong Kong during 1988-1993 were performed for 15 antimicrobial agents: erythromycin, chloramphenicol, tetracycline, minocycline, gentamicin, netilmicin, trimethoprim, rifampicin, fusidic acid, ciprofloxacin, vancomycin, teicoplanin, sparfloxacin, clinafloxacin and RP 59500 (quinupristin/dalfopristin). Susceptibility to antibiotics generally remained stable throughout the study period, with the exception of the quinolones. Resistance to ciprofloxacin (breakpoint 4 mg/L) increased from a low of 9% in 1988 to a high of 82% in 1993. For sparfloxacin the corresponding figures were 9% and 78%, respectively. Six (1%) clinafloxacin-resistant strains were found. MIC50s and MIC90s of clinafloxacin increased from < or = 0.06 mg/L and 0.25 mg/L in 1988 to 1.0 mg/L and 2.0 mg/L, respectively, in 1993. All 423 strains were phage typed (typability 70%) and a diversity of phage types which changed during the observation period, with 13 dominating types, was observed. Ciprofloxacin resistance occurred in 12 of the dominating types, in 46 non-typable strains, and also in 23 strains of different, sporadically occurring types, indicating that the emergence of quinolone resistance was not due to dissemination of a single or few MRSA clones. The usefulness of quinolones in the treatment of MRSA infections is likely to be seriously constrained by the emergence of resistance. MICs for RP-59500 were < or = 2 mg/L for all isolates, suggesting that this agent merits further evaluation as an anti-MRSA agent. All MRSA remained susceptible to vancomycin and teicoplanin throughout the study period.

Anti-Infective Agents↗
PubMed1996

A meta-analysis of studies on the safety and efficacy of aminoglycosides given either once daily or as divided doses.

We performed a meta-analysis of randomised clinical studies in which the efficacy and toxicity of the same total daily dose of aminoglycosides administered once-daily was compared with multiple divided daily dosing for treating human infections. Of twenty-eight publications identified from a literature search using Medline 19 publications of 20 study comparisons involving 2881 patients met the criteria for analysis. Netilmicin was investigated in 11 studies, amikacin in seven studies and gentamicin in two studies but no studies of tobramycin met the inclusion criteria. The meta-analysis showed that there was a small, statistically significant difference in clinical efficacy of 3.5% (95% confidence intervals 0.5% to 6.5%, P = 0.027) in favour of once-daily administration but no significant differences in bacteriological efficacy or nephrotoxicity were detected. Auditory and vestibular toxicity rates were low for all agents and no differences in these toxicities were identified between once-daily or multiple-dose administration regimens either clinically or by audiometry or electronystagmography. Aminoglycosides can be given once-daily without loss of efficacy or increased toxicity offering greater simplicity and potentially improved cost-effectiveness than can be achieved by giving these drugs in divided doses.

Aminoglycosides↗
PubMed1997

In-vitro killing activity of combinations of beta-lactam agents with aminoglycosides against penicillin-resistant pneumococci.

Streptococcus pneumoniae has developed resistance to almost every antibacterial agent used in clinical practice, including the most active beta-lactams. This has led to the proposed use of drug combinations. The aim of this study was to determine the efficacy of combinations of beta-lactam agents (cefotaxime or imipenem) with aminoglycosides (gentamicin, netilmicin or amikacin) against pneumococci showing high-level resistance to penicillin and streptomycin and/or kanamycin. All tested combinations were bactericidal and synergic despite the weak concentrations of antibiotics used. Our results suggest that combinations of beta-lactam agents with aminoglycosides may be useful for treating infections by penicillin-resistant pneumococci located outside the central nervous system.

Aminoglycosides↗
PubMed1997

Once-daily dosing of aminoglycosides: review and recommendations for clinical practice.

The use of higher-dose, extended interval (i.e., once-daily) aminoglycoside regimens to optimize bacterial killing is justified by a pharmacodynamic principle of aminoglycosides, namely concentration-dependent killing, and by the partial attribution of the toxicity of aminoglycosides to prolonged serum concentrations. Numerous in-vitro and animal studies have supported using once-daily aminoglycoside dosing. Clinical studies show at least equal effectiveness and no greater toxicity when compared with traditional regimens. A dose of 5-7 mg/kg of gentamicin, tobramycin, or netilmicin, with at least a 24 h dosing interval should be employed and a similar regimen can be applied to amikacin dosing. As yet, there are some patient populations that have not been adequately studied to determine whether or not once-daily aminoglycoside dosing would be a better choice than traditional dosing regimens.

Aminoglycosides↗
PubMed1999

Phenotypic detection of nosocomial mecA-positive coagulase-negative staphylococci from neonates.

Over a 3-year period, we screened antimicrobial resistance genotype (mecA-positive or -negative) in clinically significant coagulase-negative staphylococci isolated from patients residing in our neonatal intensive care unit. For the 152 study strains, the accuracy of standard methods (agar dilution MIC, disc diffusion and agar screen tests) in detecting oxacillin resistance during 48 h of incubation was evaluated. Using mecA gene PCR and Southern blot hybridization as the gold standard, the differential in MICs of additional antibiotics selected for their relevant clinical use in our setting was also compared with mecA status of the isolates. The frequency of mecA was 48.6% among study strains. When applying the previous (1998) and most current (1999) NCCLS interpretive criteria, the specificities of oxacillin agar dilution MICs in detecting the 78 mecA-negative isolates were 100 and 89.7%, respectively, at 24 h, and 100 and 80.7%, respectively, at 48 h. In this respect, the sensitivities of oxacillin agar dilution MICs in detecting the 74 mecA-positive strains were 75.6 and 97.2%, respectively, at 24 h, and 86.4 and 100%, respectively, at 48 h. When applying the previous and most current NCCLS zone size interpretive criteria, oxacillin zone diameters were in false-susceptible error for 13.5 and 8.1%, respectively, of the 74 mecA-positive strains tested at 24 h, and for 6.7 and 2.7%, respectively, at 48 h. Accordingly, when the 78 mecA-negative strains were considered, oxacillin zone diameters were in false-resistant error for 2.5 and 8.9%, respectively, at 24 h, and for 8.9 and 15.3%, respectively, at 48 h. The oxacillin salt agar screen assay accurately identified all mecA-negative strains at both 24 and 48 h. However, 26 (35.1%) and 7 (9.4%) of the mecA-positive strains were misinterpreted as susceptible by the agar screen test at 24 and 48 h, respectively. Using the presence of mecA as the reference standard for interpreting oxacillin susceptibility results, strains lacking mecA were more likely to be susceptible to ampicillin, ceftazidime, gentamicin, netilmicin and rifampicin than were mecA-positive strains. Vancomycin was the only antibiotic tested for which all strains, regardless of mecA status, remained susceptible.

Anti-Bacterial Agents↗
PubMed2000

Combined effects of meropenem and aminoglycosides on Pseudomonas aeruginosa in vitro.

To investigate combinations of antibiotics against Pseudomonas aeruginosa, the in vitro effects of combinations of meropenem with each of three aminoglycosides, arbekacin, amikacin and netilmicin, were evaluated using an agar dilution chequerboard technique. The combinations of meropenem and aminoglycosides were effective against almost all P. aeruginosa strains tested, which included meropenem-resistant strains. Increased synergic effects were observed in combinations that included arbekacin or amikacin. None of the combinations had an antagonistic effect. Most of the synergic and additive effects were achieved at clinically relevant concentrations.

Aminoglycosides↗
PubMed2003

Evaluation of commercial assays for vancomycin and aminoglycosides in serum: a comparison of accuracy and precision based on external quality assessment.

OBJECTIVE: To compare the accuracy and precision of commercial assay techniques in the measurement of gentamicin, tobramycin, amikacin, netilmicin and vancomycin in serum. METHODS: Data from the measurement of 40 external quality assessment samples from 358 laboratories providing a therapeutic drug monitoring service were analysed. RESULTS: Significant differences between techniques in accuracy and precision were observed for all drugs. Coefficients of variation ranged from 4.1% to 9.8% for the aminoglycosides and from 6.7% to 11.7% for vancomycin. The percentage difference in measurements from the weighed-in drug concentration ranged from -10.1% to +4.0% for the aminoglycosides and from -3.5% to +5.7% for vancomycin. The Dade Behring Emit immunoassay was notable in producing significantly more outliers (>4 S.D. from the weighed-in concentration) than other techniques in the measurement of gentamicin, amikacin and vancomycin. CONCLUSIONS: All assays performed to a satisfactory standard for measurement in non-renal patients, but none met the more stringent standards desirable for monitoring patients with renal impairment.

Anti-Bacterial Agents↗
PubMed2005

In vitro activity of citropin 1.1 alone and in combination with clinically used antimicrobial agents against Rhodococcus equi.

OBJECTIVES: The aim of this study was to investigate the in vitro activity of citropin 1.1, an antimicrobial peptide derived from the Australian tree frog Litoria citropa, alone and in combination with ampicillin, ceftriaxone, doxycycline, netilmicin, ciprofloxacin, rifampicin, linezolid, vancomycin, clarithromycin and imipenem against 12 nosocomial isolates of Rhodococcus equi. METHODS: Antimicrobial activity of citropin 1.1 was measured by MIC, MBC, time-kill studies and chequerboard titration method. RESULTS: All isolates were inhibited at concentrations of citropin 1.1 between 2 and 8 mg/L. Combination studies demonstrated synergy only when the peptide was combined with clarithromycin, doxycycline and rifampicin. CONCLUSIONS: Our findings show that citropin 1.1 is active against R. equi and that its activity could be enhanced when it is combined with hydrophobic antibiotics.

Actinomycetales Infections↗
PubMed2006

In vitro susceptibility of Bartonella species to 17 antimicrobial compounds: comparison of Etest and agar dilution.

OBJECTIVES: In vitro susceptibility testing of 31 Bartonella spp. strains including 21 Bartonella henselae isolates was performed for 17 antimicrobial agents (telithromycin, four macrolides, five fluoroquinolones, five aminoglycosides, doxycycline and rifampicin). METHODS: MICs were determined by agar dilution and Etest using chocolate agar containing 5% defibrinated sheep blood as assay medium. Longer incubation periods of 3-5 days in a humid atmosphere with 5% CO(2) were required until bacterial growth became visible and MICs could be read. RESULTS: The ketolide telithromycin was the most active agent exhibiting the lowest MICs. The Bartonella spp. were also highly susceptible to macrolides, particularly clarithromycin, and to doxycycline and rifampicin, with MICs of <or=0.12 mg/L. Gatifloxacin, gemifloxacin and moxifloxacin were the most potent fluoroquinolones, with MICs ranging from 0.06 to 2 mg/L. Netilmicin was the most active agent among the aminoglycosides. Etest MICs correlated well with MICs determined by agar dilution. CONCLUSIONS: Telithromycin, macrolides, doxycycline and rifampicin were the most effective agents against Bartonella spp. Our data confirm that Etest may be a reliable method for determining susceptibility of Bartonella spp.

Agar↗
PubMed1990

Influence of amikacin as the primary aminoglycoside on bacterial isolates in the intensive care unit.

Amikacin was introduced as the primary aminoglycoside in our hospital to prevent the further development of multiply resistant Gram-negative organisms. This study compares clinical and microbiological data before and after institution of this policy to evaluate the influence on clinical outcome in patients as well as changing resistance patterns in the respiratory ICU. Patient populations were similar in terms of severity of illness (Acute Physiology and Chronic Health Evaluation II scores), age, ventilation, invasive procedures, and the incidence of various diseases. We found that the rate of amikacin resistance increased from 8.5% to 39.6% with an increase in resistance to tobramycin (19.3% to 33.3%) and netilmicin (23.9% to 47.9%) over the same period despite minimal usage of these drugs. The clinical outcome was similar in the periods contrasted. Our findings suggest that restricting aminoglycosides to amikacin only resulted in increasing Gram-negative resistance although there was no significant effect on patient outcome.

Adolescent↗
PubMed1995

Frequency of bacteremia associated with transesophageal echocardiography in intensive care unit patients: a prospective study of 139 patients.

OBJECTIVE: To determine the occurrence rate of bacteremia associated with transesophageal echocardiography in intensive care unit (ICU) patients. DESIGN: A prospective study of 139 patients undergoing transesophageal echocardiography. SETTING: The medical ICU of a tertiary referral teaching hospital. PATIENTS: One hundred thirty-nine ICU patients (mean age 58 yrs) who underwent transesophageal echocardiography. INTERVENTIONS: Blood samples were systematically drawn for aerobic and anaerobic culture at the following times: before (blood culture 1), at the end of (blood culture 2), and 30 mins after (blood culture 3) transesophageal echocardiography examinations. MEASUREMENTS AND MAIN RESULTS: The mean duration of transesophageal echocardiography was 35 mins (range 7 to 120). One hundred thirty-four patients received mechanical ventilation; 125 patients had a nasogastric tube. Fifty-one patients had one or more underlying conditions that usually justify antimicrobial prophylaxis of bacterial endocarditis before high-risk procedures. Fifty-six patients did not receive any antibiotic treatment at the time of transesophageal echocardiography. In 114 patients, the three blood cultures were negative. In six patients, transesophageal echocardiography was performed during a preexisting bacteremia. A contamination (only one positive blood culture of the three sampling times) with coagulase-negative staphylococci occurred in four patients at blood culture 1, five patients at blood culture 2, and six patients at blood culture 3. Contamination with Corynebacterium species occurred in two patients at blood culture 2. In one patient receiving cefotaxime and netilmicin, blood culture 1 was sterile and blood cultures 2 and 3 yielded coagulase-negative staphylococci. In one patient receiving no antibiotic treatment, blood culture 1 was sterile and blood cultures 2 and 3 yielded Enterococcus faecalis. None of these two patients received a specific antibiotic treatment or developed any secondary septic focus. CONCLUSIONS: The overall frequency of bacteremia induced by transesophageal echocardiography in ICU patients was 1.4% (two of 139 patients) (95% confidence interval 0.2% to 5.1%). The frequency did not differ whether patients received antibiotics before transesophageal echocardiography (one [1.2%] of 83 patients) or not (one [1.8%] of 56 patients) (p = .96). Therefore, routine antimicrobial prophylaxis does not appear justified before transesophageal echocardiography in ICU patients.

Adult↗
PubMed1993

Multiply resistant nontyphoidal Salmonella gastroenteritis in children.

From January, 1990, to December 31, 1990, 75 children with multiply resistant Salmonella gastroenteritis were studied at the Children's Hospital "Ricardo Gutierrez" of Buenos Aires. These children ranged from 1 month to 15 years of age. Infection was community-acquired in 20 (26.6%), nosocomially acquired in 50 (66.7%) and undetermined in 5. Thirty-nine (52%) had grossly bloody stools. Fever occurred at some point in the clinical course in 61 children (81.3%) with a duration of 1 to 33 days (mean, 6.7 days). The duration of diarrhea (1 to 69 days) was longer in those who developed complications (P < 0.001). Six (8%) developed enterocolitis (2 with bowel perforation), 1 had a pulmonary abscess and 8 (11.4%) had bacteremia; 4 children died (5.3%). Salmonella typhimurium was the most common serovar (85.3%). Ninety percent minimum inhibitory concentration studies demonstrated that all strains were resistant to ampicillin (> 128 micrograms/ml), cephalothin (> 128 micrograms/ml), cefuroxime (> 128 micrograms/ml), nalidixic acid (> 256 micrograms/ml), rifampin (> 256 micrograms/ml), gentamicin (> 256 micrograms/ml) and tobramycin (256 micrograms/ml); 77.3% of strains were resistant to ceftazidime (32 micrograms/ml), 97.6% to netilmicin (> 256 micrograms/ml), 92.8% to amikacin (256 micrograms/ml), 24.4% to isepamicin (32 micrograms/ml), 5.3% to chloramphenicol (4 micrograms/ml) and 2.7% to cefoxitin (2 micrograms/ml). The 90% minimum inhibitory concentration of cefotaxime and ceftazidime was reduced by the addition of clavulanate. Aggressive multiply resistant Salmonella strains are a major pediatric problem in Buenos Aires.

Adolescent↗
PubMed2002

Chromobacterium violaceum infection in children: a case of fatal septicemia with nasopharyngeal abscess and literature review.

This previously healthy 5-year-old boy initially presented with fever and purulent conjunctivitis. The course evolved rapidly into preseptal and facial cellulitis, nasopharyngeal abscess and sepsis. Chromobacterium violaceum was isolated from conjunctival exudate and blood cultures. He received intravenous cefazolin therapy for 2 days, followed by penicillin, oxacillin and netilmicin. However, no improvement was noted, and he died on the fifth days of illness.

Abscess↗
PubMed1988

Quantitative and qualitative assessment of serum concentration monitoring and dosage adjustment of aminoglycosides.

A prospective study was carried out in 50 adult patients to determine the extent and quality of aminoglycoside serum concentration monitoring and dosage adjustment in a U.K. teaching hospital. Data were collected concerning prescription details, assay results, and subsequent dosage adjustment, methods of dosage determination, and timing of samples. Thirty-three patients received aminoglycosides without a positive culture. The mean +/- SD initial doses were 1.75 +/- 0.45 mg/kg for gentamicin and 2.33 +/- 0.55 mg/kg for netilmicin. Doses were derived from physicians' personal experience for 35 patients and using nomograms for 11 patients. Prescribed and actual administration times were observed on 218 occasions. The difference between these times were significantly different (p less than 0.005). Fifty-six trough, 61 peak, and 61 random assays were carried out, of which 48% of troughs and 56% of peaks were in the therapeutic range. Dosage regimens were calculated based on actual serum concentration assay results using the Sawchuk-Zaske method. These calculated doses were compared to actual prescribed doses for each patient. The calculated doses were greater than 120% of the prescribed doses in 78% of patients. There was a significant tendency to underdose (p = 0.001). It is concluded that the service might benefit from an individualised approach to dosage determination.

Adolescent↗