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PubMed1994

A multicentre study: Staphylococcus and Enterococcus susceptibility to antibiotics.

A multicentre study to evaluate the susceptibility of Gram-positive cocci isolated from clinical samples, was performed by six centres working in different areas of Italy. We examined 4,544 strains of Staphylococcus aureus, 4,381 strains of coagulase-negative staphylococci and 2,478 strains of enterococci. The following antibiotics were tested: penicillin G, ampicillin, amoxicillin, piperacillin, imipenem, oxacillin, ofloxacin, pefloxacin, ciprofloxacin, gentamicin, tobramycin, amikacin, netilmicin, rifampicin, clindamycin, tetracycline, cotrimoxazole, erythromycin, chloramphenicol, vancomycin and teicoplanin. Oxacillin-susceptible staphylococci confirmed their susceptibility to many other antimicrobial agents while oxacillin-resistant strains confirmed their multiple and frequent resistance to antibiotics. Resistance to oxacillin, cotrimoxazole and chloramphenicol was more frequent in coagulase-negative staphylococci than in Staphylococcus aureus. Aminoglycosides, rifampicin and quinolones were more active against coagulase-negative staphylococci than against Staphylococcus aureus. Enterococci were susceptible to penicillins and imipenem, and moderately susceptible to ciprofloxacin. Susceptibility of 70-79% was observed with high levels of aminoglycosides. Excellent results against staphylococci and enterococci were observed with vancomycin and teicoplanin.

Anti-Bacterial Agents↗
PubMedDate not supplied

Combination effect of meropenem with aminoglycosides and teicoplanin on Pseudomonas and enterococci.

The in vitro activity of meropenem, a new carbapenem, and the combination effect with netilmicin, tobramycin, gentamicin, and teicoplanin against Pseudomonas spp. and enterococci was studied. Meropenem showed very good in vitro activity against Pseudomonas aeruginosa (MIC90 2 mg/l) and good to moderate activity against Pseudomonas putida (MIC90 4 mg/l) and Enterococcus faecalis (MIC90 8 mg/l). Aminoglycosides were highly active against P. putida (MIC90 0.5 mg/l), but showed only moderate activity against P. aeruginosa. The synergistic effect of meropenem was shown in combination with teicoplanin against E. faecalis (40%). No Pseudomonas strains were inhibited by the synergistic effect of meropenem with aminoglycosides. No antagonism occurred with any of the combinations.

Aminoglycosides↗
PubMed1994

Role of granulocyte-macrophage colony-stimulating factor as adjuvant treatment in neutropenic patients with bacterial and fungal infection.

The results are presented of two preliminary studies conducted to assess the role of GM-CSF as adjuvant treatment in neutropenic patients with bacterial or fungal infections. In the first study the effect of GM-CSF on the rate of response to antibiotics was assessed. Febrile neutropenic patients (n = 91) were randomized to receive ticarcillin-clavulanate plus netilmicin with or without GM-CSF (60 micrograms/m2). Response rates were significantly higher in patients who received antibiotics plus GM-CSF (p = 0.05). An increase in neutrophil count was seen in 89% of GM-CSF patients with initial low neutrophil counts (< 100/microliters) compared with 67% of control patients (p = 0.04). In the second study the activity of GM-CSF in patients with fungal infections was assessed. Neutropenic patients with documented fungal infections received amphotericin B plus GM-CSF. Of the eight evaluable patients, six responded and four had a complete response to treatment. The neutrophil counts of the two non-responding patients did not increase substantially during GM-CSF treatment and both died of their fungal infection. The prognosis of neutropenic patients with fungal infections is usually poor and the results of this pilot study are therefore very encouraging. The two studies show that GM-CSF is able to stimulate neutrophil recovery in neutropenic patients and may improve the response to antibiotic and antifungal treatment.

Adolescent↗
PubMed1988

Mouse model for evaluation of antibiotic treatment of acute and chronic infections.

A thread model is presented which enables the simultaneous evaluation of bactericidal rate and antibiotic concentration at the site of infection in mice. Ampicillin and netilmicin were tested against both gram-positive and gram-negative bacteria. With the doses tested there was substantial drug penetration into the site of infection immediately after initiation of infection (day 0), whereas the drug penetration on days 2 and 6 of infection was delayed and reduced. On day 0 of infection there was significant bactericidal effect, but little or no effect could be demonstrated on days 2 and 6 of infection, even though drug concentrations close to the MBC values for several drug/bacteria combinations were reached. The model reflects the treatment situations for the acute and the chronic infection and may be of help in evaluating the efficacy of the drug at the site of infection.

Acute Disease↗
PubMed1989

Fat absorption in premature infants: the effect of lard and antibiotics.

Fat absorption of an adapted cow's milk formula was studied in a randomized controlled trial involving two groups of 18 premature infants (mean gestational age +/- SD: 33.0 +/- 2.9 weeks, range 26.5-37.5 weeks). The triglyceride configuration was modified by the use of lard. This modification did not improve the absorption of fat or energy. Also no difference in serum concentrations of cholesterol and triglycerides was found. Growth velocity during the study was similar in both groups. Detailed analysis of the data revealed that in infants who received (parenterally) antibiotics (mainly ampicillin and netilmicin) a higher coefficient of fat absorption (+20%, P less than 0.01) and of energy absorption (+8%, P = 0.03) was found. Based on these results, we find no support for the use of lard in adapted cow's milk infant formulas to improve fat absorption. In studies of fat and energy absorption the effects of antibiotics have to be taken into account.

Anti-Bacterial Agents↗
PubMed1993

Enterobacter cloacae cross-colonization in neonates demonstrated by ribotyping.

The intestinal colonization by Enterobacter cloacae strains with a derepressed cephalosporinase was studied in a paediatric ward between February 1990 and January 1991. Environmental sampling was performed simultaneously. Fifty-two isolates were recovered from 200 neonates (stool, blood) and 14 strains were isolated from the neonatal environment. An epidemiological study based on the typing of 36 Enterobacter cloacae isolates was carried out using antibiotyping, biotyping and ribotyping methods. The isolates selected were from 21 neonates (24 isolates), the neonatal ward environment (8 isolates) and from other wards (4 isolates). Thirty-two isolates had the same antibiotic resistance pattern, corresponding to a derepressed cephalosporinase and resistance to the following aminoglycosides: kanamycin, gentamicin, tobramycin and netilmicin. No predominant biotyping pattern could be established. Ribotyping done with two endonucleases (EcoRI and BamHI) showed 28 Enterobacter cloacae isolates to have a single pattern. Ribotyping was the most discriminating method used in this study, permitting identification of cross-contamination with Enterobacter cloacae in the paediatric ward.

Bacteremia↗
PubMed1986

In vitro activity of carumonam (RO 17-2301) and twelve other antimicrobials against clinical isolates of Pseudomonas aeruginosa.

Minimal inhibitory concentrations of the monobactam carumonam (RO 17-2301) and twelve other antimicrobials were determined using agar dilution against 140 recent non-replicate clinical isolates of Pseudomonas aeruginosa. The most active drugs were ciprofloxacin, amikacin, imipenem and ceftazidime, inhibiting 96, 91, 90 and 86 percent of the strains, respectively, at or below the susceptibility threshold. The monobactams carumonam and aztreonam were active against 78 and 65 percent of the strains, respectively. Tobramycin inhibited 68 percent of the strains, and gentamicin and netilmicin 50 and 21 percent, respectively. Analysis of correlation coefficients revealed a low correlation between imipenem and the other beta-lactams and a remarkably good correlation between the beta-lactams (excepting imipenem) and the aminoglycosides.

Aminoglycosides↗
PubMed1982

Combination effect of azthreonam with four aminoglycosides on nosocomial gram-positive cocci and non-fermenting gram-negative bacteria.

The inhibitory combination effect of azthreonam with gentamicin, tobramycin, amikacin and netilmicin respectively against 50 non-fermenting gram-negative rods and 30 gram-positive cocci was compared using the checkerboard agar dilution technique. On average 49.5% of all non-fermenting strains were inhibited by additive, and 48.5% by synergistic azthreonam-aminoglycoside combinations, but only 4.5% of the gram-positive cocci were inhibited by synergistic combinations. No antagonism occurred. No significant differences could be found between the effects of the respective azthreonam-aminoglycoside combinations.

Aminoglycosides↗
PubMedDate not supplied

Native and prosthetic valve endocarditis caused by Rothia dentocariosa: diagnostic and therapeutic considerations.

Three cases, one each of native valve, prosthetic valve and composite graft endocarditis caused by Rothia dentocariosa are described. The first patient presented with multiple brain abscesses and severe congestive heart failure due to destructive endocarditis with large vegetations on the mitral valve. He died shortly after emergency valve replacement. Gram-positive coccoid rods were identified in the vegetations of the excised mitral valve. The second patient had a R. dentocariosa endocarditis of a prosthetic aortic valve that was treated empirically with netilmicin and teicoplanin, due to an allergy to penicillin. Both antibiotics were replaced according to susceptibility testing in vitro with rifampin and ciprofloxacin, and the endocarditis was cured within 9 weeks. The third patient presented with a circular root abscess of an aortic composite graft that was successfully treated with rifampin and ceftriaxone without surgery. All patients had extensive periodontal disease which was thought to be responsible for hematogenic spread and seeding of the microorganism. The microbiological identification and antibiotic resistance pattern of the isolates, as well as therapeutic implications are discussed.

Actinomycetales↗
PubMed1990

In vitro antimicrobial susceptibility of Listeria monocytogenes isolated in the UK and other Listeria species.

The MICs and MBCs of 21 antimicrobial agents were determined for 103 strains of Listeria monocytogenes isolated in the UK and 27 strains of other Listeria species. Ampicillin, penicillin, azlocillin, imipenem, gentamicin, netilmicin, amikacin, erythromycin, rifampicin, trimethoprim, clindamycin and vancomycin had good activity, while cephalothin, chloramphenicol, ciprofloxacin and ofloxacin were less active, and cefuroxime, enoxacin, norfloxacin and fosfomycin were the least active. Tetracycline had good activity against many strains, but the MIC was high for some. Unlike the other Listeria species tested, Listeria ivanovii was susceptible to fosfomycin. Inoculum size and media employed were shown to affect the MBC, tryptose phosphate broth yielding higher MBCs than Mueller-Hinton or Isosensitest broths.

4-Quinolones↗
PubMedDate not supplied

Infective endocarditis caused by an unusual gram-negative rod, Rahnella aquatilis.

An 11-month-old girl with congenital heart disease developed infective endocarditis. Blood cultures revealed an unusual gram-negative rod, Rahnella aquatilis. The patient was successfully treated with a combination of netilmicin and ceftazidime. This is the first case report of infective endocarditis caused by this organism. R. aquatilis should be recognized as a clinical pathogen capable of causing life-threatening infection in children and adults.

Adult↗
PubMed1996

Inhibition of Pseudomonas aeruginosa alginate expression by subinhibitory concentrations of antibiotics.

The effects of subinhibitory concentrations (1/4, 1/8, 1/16 of the MIC) of quinolones (ciprofloxacin, enoxacin, nalidixic acid, norfloxacin, ofloxacin, pefloxacin), aminoglycosides (amikacin, gentamicin, netilmicin, streptomycin, tobramycin), beta-lactams (aztreonam, ceftazidime, imipenem, ticarcilin) and macrolides (erythromycin, roxitromycin) on the excretion of alginate by a P. aeruginosa strain were studied. Both beta-lactam and macrolide antibiotics were found ineffective at the concentrations tested, except erythromycin and imipenem at 1/4 MIC. Aminoglycosides at a concentration of 1/4 MIC reduced most effectively the excretion of alginate. Quinolones were also effective at this sub-MIC; 1/16 MIC was ineffective with all antibiotics or stimulated the production of alginate.

Alginates↗
PubMed2002

Characteristics of clinical Acinetobacter spp. strains.

Resistance to 13 antimicrobial agents, resistance to the bactericidal activity of human serum, hydrophobic properties, lipolytic activity and production of histamine were determined in a total of 50 clinical Acinetobacter spp. strains (A. baumannii, A. lwoffii, A. calcoaceticus, A. haemolyticus). None of the tested isolates showed resistance to meropenem and none of A. lwoffii, A. calcoaceticus and A. haemolyticus strains were resistant to amikacin. Forty-six strains (92%) manifested resistance to ampicillin, 90% to cefuroxime, 68% to ciprofloxacin, 58% to piperacillin, gentamicin and cotrimaxazole, 50% to cefotaxime, 44% to amikacin, 42% to ceftazidime, 38% to piperacillin/tazobactam, 24% to netilmicin and 16% to ampicillin/sulbactam. In particular, A. baumannii and A. calcoaceticus strains showed considerable antibiotic resistance. Thirty-one isolates (62%) showed serum resistance; intermediate sensitivity was found in 19 isolates (38%). The majority of the strains (72%) demonstrated a strongly hydrophobic character; 16% of isolates exhibited moderate hydrophobic properties. All strains showed lipolytic activity; production of histamine was detected in 14 of 43 strains examined.

Acinetobacter↗
PubMed1986

Morphological alterations in distal and collecting tubules of the rat renal cortex after aminoglycoside administration at low doses.

Ultrastructural alterations in the cortical, distal and collecting tubules have been examined in female Sprague-Dawley rats treated with various aminoglycosides in clinical use. Gentamicin, dibekacin (10 mg/kg X day), netilmicin, tobramycin (4 or 10 mg/kg X day) or amikacin (37.5 mg/kg X day) were administered intraperitoneally twice a day over different periods of time, extending from 4 to 14 days. The kidney cortex was examined after 4, 7, 10 or 14 days of aminoglycoside administration by light (semithin sections) and electron microscopy. After 7 or more days of treatment, lysosomes in collecting tubular cells (and to a lesser extent in distal tubular cells) contained concentric lamellar material (myeloid bodies), an ultrastructural alteration typical of drug-induced lysosomal phospholipidosis. Although this alteration appeared qualitatively similar to that observed in proximal tubular cells, it was less conspicuous and occurred later during treatment. In addition, distal tubular cells occasionally showed marked vacuolization and disruption of the basal cell architecture. The possible relationship between these alterations and the urine hypo-osmolality characteristic of aminoglycoside-induced renal dysfunction is discussed.

Aminoglycosides↗
PubMed2004

Antibiotic resistance rates and phenotypes among isolates of Enterobacteriaceae in French extra-hospital practice.

Antibiotic resistance among members of the family Enterobacteriaceae was prospectively surveyed by eight French private laboratories over a 5-month period in 1999. A total of 2,599 consecutive and nonduplicate strains were collected, mainly (60.9%) from patients in the community. Most strains (82.9%) derived from urine. Escherichia coli was the predominant (73.9%) organism isolated. The overall rates of antibiotic resistance were as follows: amoxicillin, 53.4%; amoxicillin-clavulanic acid, 27.3%; ticarcillin, 44.2%; piperacillin-tazobactam, 3.2%; cephalothin, 29.2%; cefuroxime, 14.7%; cefoxitin, 11.5%; ceftazidime, 3.6%; cefotaxime, 2.8%; cefepime, 0.3%; imipenem, 0.1%; gentamicin (G), 3.8%; tobramycin (T), 5.0%; netilmicin (Nt), 3.7%; amikacin (A), 0.7%; nalidixic acid, 14.3%; ofloxacin, 10.4%; cotrimoxazole, 21.1%; nitrofurantoin, 12.7%; fosfomycin, 5.2%; tetracycline, 50.1%; and colistin, 12.5%. Beta-lactam resistance phenotypes essentially comprised penicillinase production (33.9%), overexpression of chromosomal cephalosporinase (4.6%), and synthesis of inhibitor-resistant TEM/OXA enzymes (1.5%) or extended-spectrum beta-lactamases (1.5%). Aminoglycoside resistance phenotypes consisted of GTNt (93 strains), TNtA (68 strains), GTNtA (14 strains), T (4 strains), GT (3 strains), G (1 strain), and reduced uptake/permeability (3 strains). Most of the nalidixic acid-resistant strains were resistant to ofloxacin (72.8%). Antibiotic resistance rates and phenotypes varied widely according to the bacterial group and the source of the strains. Significantly higher rates were observed in private healthcare centers than in the community, due to a higher proportion of both resistant species and resistant strains. However, multidrug-resistant isolates, including five extended-spectrum beta-lactamase-producing strains, were also recovered from the community.

Ambulatory Care↗
PubMed1999

Semisynthetic aminoglycoside antibiotics: Development and enzymatic modifications.

The critical resistance mechanisms of aminoglycoside antibiotics in bacteria of clinical importance are the enzymatic N-acetylation, O-phosphorylation, and O-nucleotidylation that generally result in the inactivation of aminoglycosides. To overcome such resistance mechanisms, dibekacin (3',4'-dideoxykanamycin B) was developed as the first rationally designed semisynthetic aminoglycoside, based on the enzymatic 3'-O-phosphorylation of kanamycin. Subsequently, amikacin, netilmicin, and isepamicin were developed by introducing (S)-4-amino-2-hydroxybutyryl (AHB), ethyl, and (S)-3-amino-2-hydroxypropionyl side chains into the 1-amino group of kanamycin, sisomicin, and gentamicin B, respectively. These side chains are believed to block the access of a variety of aminoglycoside-modifying enzymes to their target sites. The latest semisynthetic aminoglycoside of clinical use in Japan is arbekacin (1-N-AHB-dibekacin), which has been extensively used since its approval as an anti-methicillin-resistant Staphylococcus aureus (MRSA) agent in 1990. Although it has several possible modification sites for aminoglycoside acetyltransferases (AACs), arbekacin-resistant MRSA strains that have emerged in the past 8 years have been those with a low or moderate level of resistance, due to a bifunctional enzyme, AAC(6')/APH(2"), at low incidence. To overcome AAC(6')/APH(2")-dependent arbekacin-resistant MRSA strains, 2"-amino-2"-deoxyarbekacin and its 5-epiamino derivative have been already synthesized. However, simulative modification studies using AACs from aminoglycoside-producing Streptomyces strains have revealed that AAC(3) and AAC(2') converted arbekacin to 3"-N-acetyl and 2'-N-acetyl derivatives, respectively, which retain high antibiotic activity. By contrast, the same acetylations of amikacin (3"-N-) and dibekacin (3-N-) resulted in their inactivation. Thus, these new findings confirmed the steric hindrance effect of the 1-N-acyl side chain and illuminated the novel aspect of arbekacin distinct from the other semisynthetic aminoglycosides, indicating that MRSA strains cannot be arbekacin-resistant even if they have acquired the aac(3) or aac(2') gene.

Journal Article↗
PubMed2002

Aerococcus urinae endocarditis: case report and review of the literature.

Aerococcus urinae is a rare cause of urinary tract infections, mainly in elderly men with underlying urinary tract pathologies. In addition, it has been described as a pathogen in balanitis, soft tissue infections, septicemia and endocarditis. To date ten cases of A. urinae endocarditis have been reported in the literature with a high rate of mortality (7/10) and morbidity, as two out of three survivors suffered from neurovascular complications. Here we present the case of an additional patient who was successfully treated with surgical valve replacement and antibiotic therapy consisting of ceftriaxone and netilmicin for 6 weeks. Furthermore, we review all reported cases of A. urinae endocarditis with emphasis on predisposing factors and therapeutic options.

Aged↗
PubMed1987

Aminoglycoside antibiotics preferentially increase permeability in phosphoinositide-containing membranes: a study with carboxyfluorescein in liposomes.

The rate of release from multilamellar liposomes of the fluorescent probe carboxyfluorescein was determined as a measure of membrane permeability. Liposomes of phosphatidylcholine and different anionic phospholipids were incubated with low (1 microM) and high (3 mM) concentrations of calcium in the absence or presence of aminoglycoside antibiotics. The leakage of carboxyfluorescein into the medium was not caused by liposomal fusion as no vesicle fusion was observed in experiments with terbium and dipicolinic acid-loaded liposomes. The basal rate of carboxyfluorescein release (in the absence or presence of 1 microM calcium) from all types of liposomes ranged from 0.1 to 0.3% of trapped carboxyfluorescein per hour. The presence of 3 mM calcium caused the greatest increase in the rate of carboxyfluorescein release (about 9-fold) in liposomes containing phosphatidylinositol 4,5-bisphosphate (PIP2) whereas liposomes containing the other anionic phospholipids (phosphatidylserine, phosphatidylinositol and phosphatidylinositol 4-phosphate) showed an approximate 5-fold increase. In the presence of 1 microM calcium, the aminoglycosides neomycin and gentamicin also increased the rate of carboxyfluorescein release, with PIP2-containing liposomes showing a 3-5-times greater response than the other liposomes, releasing up to 4.6% of trapped carboxyfluorescein per hour. This drug-induced release was dose-dependent and antagonized by calcium. In the presence of 3 mM calcium, 0.1 mM gentamicin or neomycin were ineffective while the drug at 1 mM affected carboxyfluorescein release from PIP2-liposomes only. The aminoglycoside antibiotics, neomycin, gentamicin, tobramycin, kanamycin, amikacin, netilmicin, as well as neamine and spectinomycin (all at 0.1 mM) showed a graded effect on the rate of carboxyfluorescein release from PIP2-containing vesicles in the presence of 0.1 mM calcium. The magnitude of the effect correlated well with the ototoxicity of the drugs previously determined directly in cochlear perfusions in the guinea pig. The study demonstrates that aminoglycoside antibiotics are capable of altering membrane permeabilities and that this effect is most pronounced if PIP2 is present in the bilayers. The excellent correlation between this membrane action and the in-situ toxicity of the drugs further establishes the specific role of PIP2 in the molecular mechanism of aminoglycoside-induced hearing loss. Moreover, it confirms the usefulness of such physicochemical models for the screening and prediction of aminoglycoside toxicity.

Aminoglycosides↗