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Antimicrobial use and Pseudomonas aeruginosa susceptibility profile in a cystic fibrosis centre.

The susceptibility patterns of 1315 mucoid and non-mucoid Pseudomonas aeruginosa strains from 224 patients were determined along with antibiotic utilisation in a Cystic Fibrosis Centre from 1993 to 1997. Ceftazidime was the most active agent (86.0% sensitive isolates), followed by piperacillin-tazobactam (81.7%), aztreonam (80.3%), imipenem (80%), piperacillin (76.8%), tobramycin (76.5%), ciprofloxacin (73.7%), ticarcillin (72.4%), ticarcillin-clavulanic acid (70.2%), amikacin (69.5%), netilmicin (56.5%), meropenem (79%) and imipenem (75.5%). The most frequently used compounds were nebulized colistin (mean+/-S.D., 109+/-45 defined daily doses per 1000 patients per day), followed by ciprofloxacin (98+/-8), tobramycin (55+/-9), ceftazidime (31+/-8) and amikacin (55+/-9). The mean antibiotic consumption by our CF patients was 413+/-47 defined daily doses per 1000 patients per day. Trend testing showed a significant decline of susceptibility to aminoglycosides, imipenem and ciprofloxacin, while the susceptibility of P. aeruginosa to piperacillin and ceftazidime was stable.

Adolescent↗

Outbreak of nosocomial meningitis caused by Acinetobacter baumannii in neurosurgical patients.

An outbreak of nosocomial meningitis caused by Acinetobacter baumannii, which developed postoperatively in seven neurosurgical patients is described. The clinical isolates of A. baumannii were typed by biochemical profiles and antibiogram patterns, and by random amplified polymorphic DNA polymerase chain reaction (RAPD-PCR) and amplified fragment length polymorphism (AFLP) fingerprinting. The implicated strain was multi-drug resistant, however, susceptibility to imipenem and netilmicin was detected. An extensive search for the environmental source of the epidemic strain was carried out. Two of several isolates from hospital environment, corresponded to the A. baumannii outbreak strain, one being cultured from the suctioning equipment used in the care of these patients. The introduction of multiresistant epidemic A. baumannii into a neurosurgical unit is a severe risk factor for patients undergoing neurosurgical procedures. Genotypic typing methods are important for definitive identification of these strains in patients and their environment.

Acinetobacter Infections↗

[A 4-year study of Pseudomonas aeruginosa susceptibility to antibiotics (1998-2001) in northern Lebanon].

Four hundred and sixty-four Pseudomonas aeruginosa strains were isolated in northern Lebanon at the Islami Hospital Microbiology department, in Tripoli. The purpose of this study was to evaluate the susceptibility of these strains to antibiotics, to compare this susceptibility according to the nature of the sample and the year of sampling. The results show that urinary samples were the most frequent (39.3%), followed by wound samples (21.2%), and ear samples (16.5%). The average rate of susceptible strains was 39.8% to ticarcillin, 56.9% to piperacillin, 58.2% to piperacillin + tazobactam, 74.1% to imipenem, 63.3% to ceftazidime, 60.4% to cefepime, 62.1% to aztreonam, 60.3% to netilmicin, 57.5% to gentamicin, 62.2% to tobramycin, 69% to amikacin, 100% to colistin, 45.4% to pefloxacin and ofloxacin, 57.7% to ciprofloxacin and 1.3% to rifampicin. The study showed that the strains isolated from pulmonary secretions were the most resistant to antibiotics.

Anti-Bacterial Agents↗

Tobramycin penetration into epithelial lining fluid of patients with pneumonia.

OBJECTIVE: To study the penetration of tobramycin in lung tissue evaluated as the concentration in epithelial lining fluid and to characterize the time course of the drug in the treatment of patients with pneumonia. METHODS: The subjects were 16 patients with pneumonia and taking tobramycin who had clinical indications for bronchoscopy. Bronchoscopy with bronchoalveolar lavage of the pneumonic area was performed once on each patient 1/2%, 2, 4, or 8 hours after the previous tobramycin dose. Urea was used as an endogenous marker for quantification of epithelial lining fluid obtained at bronchoalveolar lavage. Tobramycin concentrations in serum were measured for all patients at the aforementioned 4 time points. Tobramycin concentration was determined by means of fluorescent polarization immunoassay modified for bronchoalveolar samples. RESULTS: Levels of tobramycin in the fluid of the epithelial lining were 2.33+/-0.5 at 1/2 hour, 1.67+/-0.6 at 2 hours, 1.62+/-1.19 at 4 hours, and 0.77+/-0.38 microg/mL at 8 hours. The ratio of epithelial lining fluid to serum concentration of tobramycin was 0.30+/-0.03 at 1/2 hour, 0.42+/-0.16 at 2 hours, 0.64+/-0.37 at 4 hours, and 1.53+/-0.76 at 8 hours. The ratio at peak serum time was similar to that reported for tobramycin and netilmicin. CONCLUSIONS: High peak serum concentrations of tobramycin are necessary to obtain microbiologically active concentrations at the alveolar level. The fluid of the epithelial lining constitutes a deep compartment for aminoglycosides. The disappearance of tobramycin was slower than at the serum level.

Adult↗

Applications of a copper microparticle-modified carbon fiber microdisk array electrode for the simultaneous determination of aminoglycoside antibiotics by capillary electrophoresis.

A copper microparticle-modified carbon fiber microdisk array electrode was fabricated and employed in capillary electrophoresis for the simultaneous determination of the five aminoglycoside antibiotics (AGs) including netilmicin, tobramycin, lincomycin, kanamycin and amikacin. The array electrode exhibited high catalytic activity for AGs, good reproducibility and stability. Under the optimum separation conditions (separation voltage of 6.2 kV, electrophoretic medium of 125 mM NaOH), the five AGs above were baseline separated within 20 min. At a working electrode potential of 0.7 V (versus saturated calomel electrode), the calibration curves were linear over two orders of magnitude of concentration, and the detection limits (SIN=3) were below 2 microM except for lincomycin (6.7 microM). The developed method was successfully employed for the simultaneous determination of the five AGs studied in pharmaceutical injections. The feasibility of this method for the simultaneous determination of lincomycin, kanamycin and amikacin in urine sample was also demonstrated.

Aminoglycosides↗

High-performance liquid chromatographic analysis of aminoglycoside antibiotics.

A simple precolumn derivatisation method for the determination of aminoglycoside antibiotics (AGs) is described. The stability of the o-phthalaldehyde (OPA) derivatives of the AGs obtain using beta-mercaptopropionic acid (beta-MP) was investigated by reversed-phase HPLC. One of the fluorescent derivatives of sisomicin was stable at least for 6 h in 50% methanol under the optimal conditions used (OPA concentration, pH and temperature). When plasma samples spiked with sisomicin were analysed the response was linear in the calibration range of 136-900 micrograms of sisomicin per injected volume (40 microliters). As little as 0.06 micrograms of sisomicin per 1 ml of plasma could be detected with a signal-to-noise ratio > or = 2. The method was also applied to whole blood samples from rabbit after a subcutaneous injection of 1 mg/kg of the AGs using dried blood spots (DBS) on the filter-paper punched discs. The detection of sisomicin and netilmicin in the DBSs on punched discs (10.1 micrograms of whole blood) were 0.053 and 0.50 micrograms per ml of whole blood, respectively (signal-to-noise ratio > or = 2). The method permits a simple collection of blood at the microlitre level and should prove particularly useful for monitoring the AGs in blood at therapeutic levels in geriatric and paediatric patients and could be also used for the preclinical study of the AGs blood levels of a number of mice or rats without killing. An RP-HPLC method using an on-line clean-up procedure for large sample-volume analysis of serum AGs is also described.

Aminoglycosides↗

Peritonitis in continuous ambulatory peritoneal dialysis. Laboratory and clinical studies.

During a three year period, 1979-81, 82 patients were treated by continuous ambulatory peritoneal dialysis (CAPD). The incidence of peritonitis was reduced significantly during the three years from one episode per 20 patient-weeks to one episode every 37 patient-weeks. 83% of the 136 episodes of peritonitis were treated successfully by antibiotic therapy alone. 62% of the total episodes were managed successfully with intraperitoneal cefuroxime. in 13 (16%) patients, CAPD failed because of peritonitis. Hospital admission for peritonitis has been reduced to a mean of 4.3 days per patient per year of CAPD. Fron January to September, 1982, Clostridium-difficile colitis developed in 13 patients. This complication was associated with considerable mortality and morbidity and has prompted a change in antibiotic policy. Patients with peritonitis are now given intraperitoneal netilmicin and intravenous vancomycin. Peritonitis remains the main complication of CAPD, but can be minimised by development of adequate facilities for performing CAPD.

Adolescent↗

World-wide antibiotic resistance in methicillin-resistant Staphylococcus aureus.

Antibiotic resistance patterns were determined for 106 strains of methicillin-resistant Staphylococcus aureus (MRSA) from 21 countries. Resistance to gentamicin, tobramycin, netilmicin, amikacin, streptomycin, or erthromycin was recorded in more than 90% of strains. Resistance to the other compounds tested was as follows: tetracycline 86%, minocycline 76%, trimethoprim 69%, clindamycin 66%, neomycin 59%, chloramphenicol 39%, rifampicin 26%, fosfomycin 22%, ciprofloxacin 17%, fusidic acid 12%, bacitracin 2%, and novobiocin 1%. All the stains were sensitive to mupirocin, pristinamycin, ramoplanin, teicoplanin, and vancomycin. There were geographical patterns of resistance: MRSA from the UK and Australia were predominantly resistant to trimethoprim, whereas many strains from centres in Europe and the USA were sensitive. MRSA that were resistant to ciprofloxacin were of French and German origin. 15 strains, 12 of which came from France, Turkey, or Brazil, were resistant either to thirteen or to fourteen agents.

Administration, Topical↗

Antibiotic resistance among gram-negative nosocomial pathogens in the intensive care unit: results of 6-year body-site monitoring.

Results of 6-year body-site monitoring in an intensive care unit (ICU) are presented and antimicrobial resistance of gram-negative isolates analyzed. The study included 622 patients. Six hundred thirty-five bacterial isolates-causes of nosocomial sepsis, pneumonia, and urinary tract infections (UTIs)-were tested during the study. Gram-negative bacteria were the predominant isolates, causing 65% of cases of sepsis, 78.7% of pneumonias, and 70.2% of UTIs. Gram-negative isolates (454) were highly resistant to antimicrobials commonly used in the ICU, with the exception of imipenem. Resistance was 1.1% among pathogens responsible for UTIs, 6.7% among those causing sepsis, and 13.6% among those responsible for pneumonia. Klebsiella pneumoniae associated with pneumonia and sepsis was significantly less resistant to ciprofloxacin than were isolates from urine (22.8% and 13.9%, respectively, vs 44.4%). Pseudomonas aeruginosa strains responsible for pneumonia were less resistant to ceftazidime than were isolates causing sepsis and UTI (35.7% vs 51.3% and 51.5%, respectively). Acinetobacter calcoaceticus strains associated with UTI were significantly more resistant to netilmicin than were strains responsible for sepsis and pneumonia (83.3% vs 40.3% and 42.6%, respectively). The study confirmed that in addition to focused microbiologic surveillance, multiple-body-site monitoring can provide unique information about the sensitivity of the pathogens involved. The results suggest that antimicrobial resistance among nosocomial pathogens depends on the site of infection or the type of microbiologic specimen.

Acinetobacter calcoaceticus↗

Peritonitis in children on continuous ambulatory peritoneal dialysis.

Between 1979 and 1985, 26 patients on continuous ambulatory peritoneal dialysis had 97 episodes of peritonitis. These occurred over a period of 336 patient months, giving an incidence of one episode every 3.5 patient months. The micro-organisms comprised Gram-positive and Gram-negative bacteria as well as fungi which accounted for six episodes. Gram-positive bacteria were isolated in 49 of the 97 episodes (50.5%) with Staphylococcus epidermidis predominating. The incidence of culture-negative peritonitis was high (27.8%). Because of failure to respond to treatment, or because of frequent recurrences, 42% patients were transferred to haemodialysis. The changing bacterial ecology has necessitated an alteration in choice of antibiotics. Cefamandole and/or gentamicin are no longer appropriate since 46% strains of S. epidermidis are now methicillin-resistant. Our 'best guess' choice for bacterial peritonitis would now start with netilmicin, vancomycin being added if indicated. For fungal peritonitis we would now start with a primary course of anti-fungal agents followed by early removal of the catheter if there is no response to treatment.

Adolescent↗

Bacteriology of burns.

A retrospective study was undertaken at University College of Medical Sciences and Guru Teg Bahadur Hospital, Delhi, to examine the bacterial isolates from the Burns unit and to determine the antibiograms of the isolates to commonly used antimicrobial agents. A total of 600 pus samples from as many patients received, over a period of 5 years (June 1993-June 1997) yielded 920) isolates. Pseudomonas spp. was the most common (36%) followed by Staphylococcus aureus (19%), Klebsiella spp. (15.54%), Proteus spp. (11.19%), Enterococcus faecalis (8.5%), Escherichia coli (5.10%), Acinetobacter spp. (1.1%), Salmonella senftenberg (0.8%) and other (3%). Pseudomonas spp. was the most susceptible to ceftazidime (83% susceptible) and cefoperazone (82% susceptible), whereas the drugs most effective in other Gram-negative organisms were amikacin, netilmicin and ciproflox. Vancomycin was effective in 100% of Gram-positive organisms. The infection of burn wounds with multiple organisms, with the superadded problem of drug resistance, necessitate the institution of a drug policy by the hospitals for burn patients.

Anti-Bacterial Agents↗

[Antibiotic resistance of Staphylococcus aureus in urban experience: 6 month study in Aquitaine].

Antibiotic resistance of Staphylococcus aureus has been surveyed by eight city laboratories of the Aquitaine area, during a six month-period (january to june 1998). Antibiotic susceptibility testing has been performed by the disk diffusion method, and the results have been collected and analysed using the SIRscan system. After elimination of the redundant strains, a total of 747 isolates has been retained. They were mainly isolated from pus (64%) collected from patients of the community (40%) or hospitalized in 30 private clinics or nursing homes. The percentages of resistant strains (community/institutions) were: benzylpenicillin: 90% (87/92%), oxacillin: 39% (23/50%), kanamycin: 37% (22/47%); gentamicin: 13% (8/16%), tobramycin: 37% (21/47%), amikacin: 21% (13/27%); netilmicin: 6% (5/7%), erythromycin: 33% (30/35%), spiramycin: 72% (77/69%), lincomycin: 24% (17/29%), pristinamycin: 2% (1/2%), tetracycline: 17% (14/19%); pefloxacin: 40% (25/50%), fosfomycin: 9% (6/12%), rifampicin: 10% (7/13%), fusidic acid: 14% (11/15%), cotrimoxazole and vancomycin: 0%. Meticillin-susceptible strains of S. aureus were mostly sensitive to other antibiotics (< or = 6% resistant strains, except for erythromycin: 22%). Among meticillin-resistant S. aureus, heterogeneous strains with a KT phenotype, and various resistance patterns to the remaining antibiotics were predominant (61%), compared to the homogeneous strains with a KTG phenotype and multiresistant to the other antibiotics (32%). The frequencies of resistant strains were highly variable depending on the specimen, the laboratory and the health care institution, except for cotrimoxazole and vancomycin which were always active.

Anti-Bacterial Agents↗

High-performance liquid chromatographic determination of isepamicin in plasma, urine and dialysate.

A high-performance liquid chromatographic method for the measurement of isepamicin, a new aminoglycoside, in plasma, urine and dialysate is reported. The assay utilizes a simple extraction of isepamicin in plasma using commercially available Cyano solid-phase cartridges and dilution of urine and dialysate samples. The separation is performed on a Hypersil C18 column (15 cm X 4.6 mm I.D., 5 microns particle size) and utilizes a mobile phase consisting of 10% methanol and 90% buffer solution containing 0.01 M sodium hexanesulfonate, 0.1 M sodium sulfate and 17 mM acetic acid. The flow-rate is 1.1 ml/min. Dibekacin is used as the internal standard. Isepamicin is derivatized post-column with o-phthalaldehyde for spectrofluorometric detection. The method can also be used for the measurement of other aminoglycosides, i.e. tobramycin, kanamycin, netilmicin and gentamicin. The assay is fast, accurate and has a quantitation limit of 100 ng/ml isepamicin in plasma and 50 ng/ml in urine and dialysate.

Aminoglycosides↗

A simple method for the assay of colistin in human plasma, using pre-column derivatization with 9-fluorenylmethyl chloroformate in solid-phase extraction cartridges and reversed-phase high-performance liquid chromatography.

A simple, selective and sensitive high-performance liquid chromatographic (HPLC) method is described for the determination of colistin in human plasma. Derivatization with 9-fluorenylmethyl chloroformate was performed in the same solid-phase extraction C18 cartridge used for sample pre-treatment, followed by reversed-phase HPLC with fluorimetric detection. Quantification was achieved using the ratio of the summed peak areas of colistin A and B derivatives to that of the derivative of netilmicin (internal standard). Linear calibration curves were obtained within the concentrations of colistin sulfate from 0.10 to 4.0 mg/l in plasma. Accuracy was within 10% and reproducibility (RSD) was less than 10%.

Calibration↗

Relationship between ototoxicity of aminoglycoside antibiotics and their transferability into inner ear fluids.

The purpose of this study is to clarify the question whether the difference of severity of ototoxicity induced by the aminoglycoside antibiotics depends on the difference of quantity of transferability into inner ear. Aminoglycoside antibiotics (tobramycin, kanamycin, netilmicin and ribostamycin) were injected for 30 consecutive days to rabbits. The relationship between the severity of hair cell damage and concentration of antibiotics in perilymph was investigated. The drug concentration in the perilymph was determined by the bioassay method, and using the surface preparation technique the hair cell damage was observed under a phase contrast microscope. It was concluded that the difference of severity of ototoxicity induced by the aminoglycoside antibiotics is due to the difference of their own toxicity to hair cells but not to the difference of their transferability into the perilymph.

Aminoglycosides↗

[Impact of initial antibiotic therapy on the course of resistance to fluoroquinolones and aminoglycosides in Gram-negative bacilli isolated from intensive care patients].

OBJECTIVE: To evaluate the effect of the initial antibiotic therapy associating a betalactam antibiotic (BLA) with either an aminoglycoside (AG) or a fluoroquinolone (FQ) on the development of resistance of gram-negative bacilli in an intensive care unit. STUDY DESIGN: Prospective bacteriological surveillance study. PATIENTS: The study included 51 patients experiencing a second infection with gram-negative organisms, eight days or more after a first infection. METHOD: The incidences of bacterial infection and the antimicrobial susceptibility have been assessed. RESULTS: The first-choice therapy was based either on BLA + AG (51%), or on BLA + FQ in the others (46%). The causative organisms were Enterobacteriaceae (57%) and Pseudomonas aeruginosa (31%). The second infection occurred 23 +/- 11 days after the first. The main organisms involved were Pseudomonas aeruginosa (51%) and Enterobacteriaceae (41%). In the group treated initially with an AG, only the antibiotic susceptibility for amikacin decreased significantly (72 vs 36%, p < 0.05). The latter was the most prescribed antibiotic (56%). In the FQ group, there was a significant decrease of susceptibility for ciprofloxacin, pefloxacin, netilmicin and tobramycin. The decrease was not significant for gentamicin and amikacin. CONCLUSIONS: In intensive care patients, the use of FQ in association with a BLA increases the resistance to AG and FQ. Therefore it seems preferable to administer an AG in association with a BLA. Amikacine should only be prescribed when justified for a given case.

Aminoglycosides↗

Impact of an educational program on antibiotic use in a tertiary care hospital in a developing country.

A multi-cross-sectional study was conducted in a 2000-bed tertiary care university hospital in Bangkok, Thailand, from September 1993 to May 1994 to assess the effectiveness of an educational program on the use of antibiotics. Data on the study covered antibiotic usage both in-patients and out-patients. Data were collected for a 24-hour period every 2 weeks for 7 days for each 3-month period. The target population were residents, general practitioners, and sixth-year medical students. The educational program provided information derived from the data of inappropriate use of antibiotics during the pre-intervention period and guidelines on the use of antibiotics which were agreed to by a consensus among the faculty in all clinical departments. The study revealed: (1) the prevalence of antibiotic use and the cost of antibiotics during post-intervention period was significantly decreased by 20%; (2) the use of antibiotic prophylaxis for obstetrics patients and patients undergoing cataract surgery decreased significantly; (3) there was a shift from second or third generation cephalosporins to cefazolin for surgical prophylaxis; (4) the duration of perioperative antibiotic prophylaxis was reduced to under 2 days; (5) there was a shift from netilmicin or amikacin to gentamicin for the treatment of community acquired infection; and (6) the mortality, median length of hospital stay, and nosocomial infection rate among the patients who received antibiotics during the post-intervention period were not significantly different from those during the pre-intervention period. These results suggest that this educational program comprising information feedback and antibiotic usage guidelines was effective in improving antibiotic use at this tertiary care university hospital in Thailand.

Anti-Bacterial Agents↗