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Therapeutic efficacy of granulocyte colony-stimulating factor alone and in combination with antibiotics against Pseudomonas aeruginosa infections in mice.

The therapeutic efficacy of granulocyte colony-stimulating factor (G-CSF) against an experimental intramuscular infection induced by Pseudomonas aeruginosa in mice was confirmed. Bacterial growth in the infected thigh muscle was suppressed by G-CSF treatment. The change in the number of peripheral blood polymorphonuclear leukocytes (PMN) after bacterial challenge was investigated. The results showed that G-CSF could stimulate stronger defense mechanisms after stimulation by bacterial challenge. In the G-CSF-treated group, more clusters of matured PMN were observed in the infected thigh muscle 6 h after bacterial challenge. Next, the correlation between the number of PMN in the blood at the time of infection and the therapeutic efficacy of antibiotics was investigated. The therapeutic efficacy of ceftazidime, a beta-lactam antibiotic, was affected by the number of blood PMN at the time of infection. In particular, a decrease of peripheral blood PMN at the time of infection resulted in a dramatic decrease in the efficacy of ceftazidime. The reduction in leukopenia by G-CSF remarkably strengthened the therapeutic effect of antibiotics in mice.

Animals↗

Comparative analysis of two rapid automated methods and a semiautomated version of the urease method for determining aminoglycoside concentrations in serum.

The Syva EMIT Autolab 6000 and the Abbott TDX automated methods for measuring serum aminoglycoside concentrations were compared with each other and with a new semiautomated version of the urease technique. Each was evaluated for accuracy, reproducibility, cost, and ease of use. All three methods gave satisfactory results, although the Abbott TDX was the most accurate. Both automated methods gave results within minutes, whereas the new urease method, which involved more initial manipulation, took 1.25 h to complete (mainly incubation time). There was no difference in accuracy of performance between experienced and inexperienced operators. The new urease method was much cheaper in terms of initial capital expenditure and in cost per test and needed no provision of manufacturer's back-up maintenance services. This could prove invaluable in situations where financial resources are at a premium. Otherwise, the Abbott TDX is currently our method of choice, and reasons for its preference to the EMIT system are listed.

Anti-Bacterial Agents↗

Multiple breakpoint method for measuring effect of antibiotics on endocarditis strains of streptococci.

The activity of penicillin alone and combined with aminoglycoside on endocarditis strains of streptococci was examined. Good assay reproducibility was obtained by the use of logarithmic phase cultures standardised by opacity, careful inoculation of well-plates, removal of antibiotic by membrane transfer and incubating survival counts in hydrogen plus carbon dioxide. The use of 10-fold intervals for penicillin concentration simplified assay design without loss of efficiency.

Drug Therapy, Combination↗

Association between antibiotic resistance and the expression of Dr adhesin among uropathogenic Escherichia coli.

BACKGROUND: Urinary tract infections (UTIs) are a significant health problem and Escherichia coli has been exported to be the primary pathogen in approximately 80% of cases. E. coli express structures called adhesins, fimbriae or pili that help them bind to specific tissue receptors. One such adhesin is Dr, which binds to the complement decay-accelerating factor (CD55) on the host cell. The purpose of the present study was to review the epidemiology and antimicrobial sensitivity spectrum of Dr adhesin-bearing E. coli isolates in women with UTI. METHODS AND RESULTS: A total of 337 uropathogenic E. coli isolates were collected, and mannose-resistant hemagglutination was observed in 43%, while 12.4% expressed Dr adhesin. All 337 uropathogenic E. coli isolates were found to be resistant to penicillin, oxacillin, bactericin and cloxacillin. None of the isolates was resistant to quinolones. The resistance to sulfamethoxazole was most common (90%), followed by nalidixic acid (51%) and ampicillin (41%). Interestingly, uropathogenic E. coli expressing Dr adhesin had a high incidence of ampicillin resistance (83%), and only 17% of the Dr-bearing isolates were found to be resistant to an ampicillin/sulbactum combination. CONCLUSION: These results indicate that UTIs may be successfully treated with ampicillin in combination with a beta-lactamase inhibitor, so that selective colonization by Dr adhesin-bearing uropathogenic E. coli is prevented, which is probably promoted by treating these patients with ampicillin alone.

Adhesins, Escherichia coli↗

Left atrial myxoma prolapsing into the left ventricle. Case report and review of the literature.

Cardiac myxomas are rare tumors which may present differently. Left atrial myxoma is an entity from anatomopathological and clinical aspects. To the best of our knowledge, only 2 cases of infected left atrial myxomas treated surgically have been reported in the last 6 years. Herein, we present a patient with a left atrial myxoma prolapsing into the left ventricle in the diastolic phase, which was infected with Streptococcus viridans. Combined therapy, consisting of surgical management and antimicrobial therapy, was used. Clinical presentation, diagnosis and treatment are reviewed.

Anti-Bacterial Agents↗

Bullous erysipelas: clinical presentation, staphylococcal involvement and methicillin resistance.

BACKGROUND: Erysipelas is a bacterial infection of the dermis and hypodermis, mostly of streptococcal origin. Bullous erysipelas represents a severe form of the disease. OBJECTIVE: To evaluate the clinical and microbiological characteristics and treatment of bullous erysipelas. METHODS: Patients with a diagnosis of bullous erysipelas who were treated at the Department of Dermatology, University Hospital of Heraklion, Crete, Greece, between the years 1996 and 2001 were retrospectively studied. RESULTS: Fourteen patients (11 women, 3 men) with bullous erysipelas were evaluated. The lesions were located on the legs and face in 9 and 4 patients, respectively. The median duration of disease before hospital admission was 4 days. Eight patients had fever at presentation. Local trauma and various lesions were common causes for pathogen entry. The initial empirical antibiotic treatment included intravenous beta-lactams and was modified according to the sensitivities of the isolated strains. Staphylococcus aureus was isolated from 7 (50%), while S. warneri, Streptococcus pyogenes and Escherichia coli grew from the lesions of 3 other patients. Six out of 7 S. aureus strains were methicillin resistant (MRSA) but susceptible to several other non-beta-lactam antibiotics such as quinolones, vancomycin, rifampicin and trimethoprim/sulfamethoxazole. CONCLUSION: Our findings suggest that S. aureus is frequently involved in and probably contributes in synergy with beta-hemolytic streptococci to the complicated course of bullous erysipelas. The frequency of MRSA isolation suggests that beta-lactam antibiotics may not be sufficient for the treatment of bullous erysipelas anymore, at least in areas with a high incidence of MRSA strains. The role of other classes of antibiotics providing adequate coverage for MRSA has to be evaluated in prospective clinical trials.

Adult↗

Activation of aminoglycoside antibiotics to cytotoxins.

We have previously postulated an enzymatic transformation of gentamicin (to a metabolite or an 'activated' molecule) as part of its ototoxic action. Here we test with eight aminoglycosides whether the proposed mechanism applies to these antibiotics as a group. Drugs were activated by incubation with a subcellular fraction from liver, and cytotoxicity was tested in a bioassay using isolated outer hair cells from guinea pig. None of the aminoglycosides compromised the viability of the cells when assayed directly, i.e. without a preceding activation. In contrast, all clinically ototoxic aminoglycosides tested were significantly cytotoxic following the incubation. Neamine, considered to be non-ototoxic, did not yield a cytotoxin. A subcellular fraction from cochlear lateral wall tissues also converted gentamicin to a cytotoxin. The results support the hypothesis that activation of aminoglycosides precedes their toxic actions and demonstrate that the capability for activation is not confined to liver.

Animals↗

Hyperacute unilateral gonococcal endophthalmitis in an HIV-infected man without genital infection.

PURPOSE: To demonstrate the necessity of obtaining an accurate history from patients presenting abnormal evolution of ophthalmologic diseases. METHODS: A 42-year-old patient, denying any previous ocular or systemic morbidity, presented with an unusual severe and hyperacute gonococcal endophthalmitis with corneal abscess but no concurrent genitourinary infection. Only after a further interview did the patient reveal his human immunodeficiency virus status and a previous diagnosis of acquired immunodeficiency syndrome. RESULTS: Adequate topical and intravenous antibiotic treatment and surgery led to salvage of the eye. CONCLUSIONS: An accurate history should be obtained by patients with an abnormal course of an ophthalmologic disease, focusing on immunologic deficiencies that can cause extremely serious ophthalmologic complications with ensuing risk of visual impairment or ocular loss (bulbar enucleation).

Abscess↗

Efficacy of collagen shields after extracapsular cataract extraction.

The efficacy of presoaked porcine collagen shields was compared with subconjunctivally injected corticosteroids and antibiotics in reducing ocular inflammation after ECCE with IOL implantation, and signs of reduced oxygen delivery to the cornea were assessed. Fifty eyes of fifty patients were recruited. At the end of surgery 25 eyes (group 1) received a 24-h shield presoaked with 0.1% betamethasone disodium phosphate and 0.5% netilmycin. The other 25 eyes (group 2) received 1 mg betamethasone disodium phosphate and 250 mg piperacillin as a subconjunctival injection. The eyes were then taped closed. Inflammatory parameters (anterior chamber flare, fibrin, folds of Descemet's membrane, corneal edema) and tolerability of the delivery system (pain, itching) were evaluated 24 h after surgery. None of the patients lost the shield and the collagen devices were well tolerated. Groups 1 and 2 showed no significant differences in the parameters considered. There was, however, transient, slight diffuse superficial corneal edema in 24% of group 1 and 4% of group 2, raising the question of inadequate oxygen transmission through collagen shields under closed lids. The results suggest that collagen shields used with the right solution have no significant adverse effect and may be a less invasive alternative to subconjunctival injection.

Betamethasone↗

Use of the quinolones for the prophylaxis and therapy of infections in immunocompromised hosts.

The prevention and treatment of infections are major issues of supportive care in patients with haematological malignancies. Because of their broad antimicrobial activity, the use of fluoroquinolones for prophylaxis in neutropenic patients has been extensively studied. In comparison with placebo, norfloxacin reduces the incidence of Gram-negative infections, whereas Gram-positive bacterial and fungal infections remain unaffected. Ofloxacin and enoxacin also bacterial and fungal infections remain unaffected. Ofloxacin and enoxacin also produce a reduction in fever and documented infections. In randomized studies comparing ciprofloxacin with cotrimoxazole (trimethoprim/sulfamethoxazole) plus colistin (each in combination with nonabsorbable antifungal agents), conflicting results were obtained. The incidence of documented Gram-negative bacterial infections was markedly reduced by ciprofloxacin prophylaxis; however, the number of Gram-positive infections may increase dramatically. Combining ciprofloxacin with a macrolide antibiotic in an attempt to prevent streptococcal infections can result in breakthrough bacteraemias due to resistant Gram-positive pathogens. Empirical antimicrobial therapy after quinolone prophylaxis should also be directed against microorganisms susceptible to quinolones, since sustained eradication by oral administration cannot be assumed with certainty. Clinical trials comparing intravenous quinolones in combination with aminoglycosides with widely used standard regimens for the treatment of infections in cancer patients indicate equivalent efficacy; however, in studies of ciprofloxacin alone, response rates were significantly lower compared with standard combinations. Therefore, quinolone monotherapy as empirical treatment in febrile neutropenic patients cannot be recommended.

Anti-Infective Agents↗

Gentamicin in 1978.

For a decade gentamicin has been used extensively because of its antimicrobial efficacy and the relatively low prevalence of clinical toxicity. Recently the more frequent appearance of resistant organisms, reports of increased nephrotoxicity and ototoxicity, and the development of newer aminoglycoside antibiotics have raised doubts about the continued use of this agent. This paper reassesses the role of gentamicin. It is clear that an appreciation of the pharmacokinetics and the clinical use of gentamicin as well as an understanding of the patterns of toxicity in animals and humans can lead to more efficient treatment with this antimicrobial agent. Despite ample competition from a number of newer aminoglycoside antibiotics, gentamicin will probably continue to be used widely in the near future.

Amikacin↗