Surface-modified antiasthmatic dry powder aerosols inhaled intratracheally reduce the pharmacologically effective dose

PURPOSE: A new particle design method to improve the aerosolization properties of a dry powder inhalation system was developed using surface modification of hydrophobic drug powders (pranlukast hydrate) with ultrafine hydrophilic particles, hydroxypropylmethylcellulose phthalate (HPMCP) nanospheres. The mechanism of the improved inhalation properties of the surface-modified particles and their deposits on carrier particles (lactose) was clarified in vitro. METHODS: Drug particles were introduced to aqueous colloidal HPMCP dispersions prepared by emulsion-solvent diffusion techniques followed by freeze- or spray-drying of the resultant aqueous dispersions. The surface-modified powders obtained with HPMCP nanospheres and their mixture with lactose powders were aerosolized by Spinhaler and their mode of deposition in lung was evaluated in vitro using a twin impinger. To elucidate the inhalation mechanism of these surface modified particles, we measured their modified micromeritic properties, such as surface topography, specific surface area, dissolution rate, and dispersibility in air. RESULTS: Dramatically improved inhalation properties of the surface modified powder, i.e. a two-fold increase in emission and a three-fold increase in delivery to deep lung, were found in vitro compared with the original unmodified powder. Improved inhalation was also found with the surface-modified drug deposited on lactose particles. Those improvements were attributed to the increased surface roughness and hydrophilicity of the surface-modified particles, and the resultant increased dispersibility in air. CONCLUSIONS: Surface modification of hydrophobic drug particles with HPMCP nanospheres to improve hydrophilicity was extremely useful in increasing the inhalation efficiency of the drug itself and the drug deposited on carrier; this was attributed to increased dispersibility in air and emission from the device, for spray- and freeze-dried particles, respectively.     

Kinetics of immunological responses, resistance to reinfection, and pathological reactions to infection with Trichinella spiralis

Changes in immune responses, resistance to reinfection, and pathological reactions were studied serially in mice that had been infected for four to 40 weeks with 150 larvae of Trichinella spiralis. Immediate footpad hypersensitivity reactions to antigens of Trichinella were present throughout the period of observation. Delayed hypersensitivity reactions 48 hr after injection of antigen were first seen in mice infected for 14 weeks and gradually increased in size thereafter. Intestinal adult worm burdens were determined one week after challenge with 5000 larvae. There was resistance to reinfection and accelerated expulsion of worms in animals challenged three weeks after the primary infection; this resistance waned at seven and 13 weeks but reappeared in mice infected for 20 weeks or longer. Counts of larvae in muscle were determined four weeks after challenge with 5000 larvae. Marked resistance was present four weeks after the primary infection and was maintained for the duration of the study.     

Pneumoperitoneum does not potentiate the nephrotoxicity of aminoglycosides in rats

OBJECTIVES: Pneumoperitoneum is associated with transient renal dysfunction. To our knowledge, the safety of administering nephrotoxins such as aminoglycosides during pneumoperitoneum has not been studied. Our hypothesis was that pneumoperitoneum potentiates the nephrotoxicity of aminoglycosides. METHODS: From 29 rats we obtained preprocedure 24-hour urine collections. In the pneumoperitoneum group (n = 7), carbon dioxide was insufflated intra-abdominally at 15 mm Hg pressure for 2 hours. In the gentamicin group (n = 7), 10 mg/kg gentamicin was administered intravenously. In the combined pneumoperitoneum/gentamicin group (n = 8), the same dose of gentamicin was administered 10 minutes before pneumoperitoneum. Sham rats (n = 7) received anesthesia only. Urine was collected for the 24 hours after the procedure, and 1 week later blood for creatinine determination and final 24-hour urine collections were obtained. All urine samples were assayed for creatinine and N-acetyl-beta-glucosaminidase (NAG). RESULTS: Only the gentamicin and combined pneumoperitoneum/gentamicin groups presented day 1 values for NAG excretion that were significantly greater than same day sham or paired preprocedure values; the rest of the urinary creatinine and NAG day 1 levels and all the day 7 levels were not significantly different from same day sham or paired preprocedure levels. Day 7 serum creatinine and creatinine clearance did not differ significantly among the groups. CONCLUSIONS: We found that intravenous gentamicin transiently increased urinary excretion of NAG in rats, which resolved within 1 week. Pneumoperitoneum for 2 hours at 15 mm Hg did not increase urinary NAG, either alone or in gentamicin-treated rats. Moreover, our data are sufficient to refute with 95% certainty the possibility that gentamicin plus pneumoperitoneum decreases creatinine clearance more than approximately 60%. These results do not support the hypothesis that pneumoperitoneum potentiates the nephrotoxicity of aminoglycosides.     

Subacute bacterial endocarditis due to Actinobacillus actinomycetemcomitans. Report of a case with a review of the literature

A case of subacute bacterial endocarditis due to Actinobacillus actinomycetemcomitans is reported. The patient was successfully treated first by a combination of gentamicin and ampicillin and then, because of severe allergic reactions, ampicillin was replaced by co-trimoxazole; symptoms did not recur and blood cultures remained sterile. A synoptic table is presented of 19 reported cases of infection caused by A. actinomycetemcomitans not connected with actinomycosis, with particular regard to their clinical features, treatment, and outcome.     

Local immune responses to Chlamydia pneumoniae in the lungs of BALB/c mice during primary infection and reinfection

Cell-mediated immune (CMI) responses play a major role in protection as well as pathogenesis of many intracellular bacterial infections. In this study, we evaluated the infection kinetics and assessed histologically the lymphoid reactions and local, in vitro-restimulated CMI responses in lungs of BALB/c mice, during both primary infection and reinfection with Chlamydia pneumoniae. The primary challenge resulted in a self-restricted infection with elimination of culturable bacteria by day 27 after challenge. A mild lymphoid reaction characterized the pathology in the lungs. In vitro CMI responses consisted of a weak proliferative response and no secretion of gamma interferon (IFN-gamma). The number of lung-derived mononuclear cells increased substantially during the primary infection; the largest relative increase was observed in B cells (B220(+)). After reinfection, the number of lung-derived mononuclear cells increased further, and the response consisted mainly of T cells. The reinfection was characterized in vivo by significant protection from infection (fewer cultivable bacteria in the lungs for a shorter period of time) but increased local lymphoid reaction at the infection site. In vitro, as opposed to the response in naive mice, acquired immunity was characterized by a strongly Th1-biased (IFN-gamma) CMI response. These results suggest that repeated infections with C. pneumoniae may induce Th1-type responses with similar associated tissue reactions, as shown in C. trachomatis infection models.     

Characterization of HEp-2 cell projection formation induced by diffusely adherent Escherichia coli

Diffusely adherent Escherichia coli (DAEC) are diarrheagenic E. coli whose pathogenetic mechanisms are largely unknown. DAEC have been shown to induce an unusual phenotype upon adherence to HEp-2 cells in culture characterized by the induction of long thin membrane processes extending from the cell surface. In addition, DAEC have been shown to be protected from the bactericidal effects of gentamicin when incubated with HEp-2 cells. In our studies, we found that three DAEC strains induced formation of eukaryotic cell processes and were protected from gentamicin killing after a 3 h incubation. Preincubation of HEp-2 cells with colchicine or cytochalasin D prior to infection with DAEC strain C1845 resulted in decreased projection formation, suggesting that the effect was dependent upon microfilament and microtubule rearrangement. When the standard gentamicin protection assay was extended for an additional 3 h incubation in the presence of gentamicin, a greater number of DAEC survived gentamicin treatment, more eukaryotic projections were seen in association with the bacteria and the bacteria were actually observed to be "embedded' within these projections. Projection formation was not observed when the bacteria were separated from the cells by a permeable membrane or when the inoculum was inactivated by ultraviolet irradiation. Transposon TnphoA mutants of C1845 were screened for decreased gentamicin protection. All three mutants which were deficient in gentamicin protection demonstrated less projection formation. Insertion mutations affecting gentamicin protection were localized to both the chromosome (two) and a plasmid (one). Eukaryotic projections are a novel interaction of DAEC with epithelial cells, may play a role of the survival of the bacteria against host defenses and may contribute to DAEC pathogenesis. The effect is dependent upon epithelial cell contact and requires multiple bacterial genes.     

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Abstract

Bone ingrowth into and through porous coatings on orthopaedic implants can substantially improve fixation. However, the introduction of pores increases surface roughness and also the risk of bacterial adherence, which can lead to infection (in extreme cases, to death) and complicate implant surgery due to the high risk of revision being required. Improving osseointegration without increasing infection risk is therefore a major challenge in implantology. Staphylococcal adhesion and biofilm formation on Ti surfaces of varying roughness and porosity have been investigated in vitro. Porous pure titanium coatings, obtained by a PM processing route based on the electrophoretic deposition of TiH₂ followed by thermal treatment in vacuum, significantly reduced bacterial colonisation of the surface compared with a state-of-the-art vacuum plasma sprayed coating. Further reduction of biofilm formation could be obtained by additional surface modification.     

18CrNiMo7-6合金钢表面变质层循环特性

 为了研究18CrNiMo7-6合金钢表面变质层在循环加载作用下的本构特性,对18CrNiMo7-6合金钢进行了渗碳热处理,通过化学腐蚀得到不同表面变质层厚度的圆棒试样,并分别进行单调拉伸试验和循环加载试验分析其力学性能、滞回性能、耗能能力及微观组织的区别。对不同表面变质层厚度18CrNiMo7-6合金钢在循环加载作用下的骨架曲线进行拟合,研究其与单调拉伸作用下的力学性能区别。基于Chaboche循环本构模型标定了不同表面变质层厚度试样在循环加载作用下的循环本构参数,并通过有限元软件ABAQUS进行了仿真验证。结果表明,在单调拉伸作用下,随着表面变质层厚度的增加,试样的硬度、屈服强度及抗拉强度也随之提高。在相同的应变幅值加载下,表面变质层越厚,其响应应力越大,能量耗散系数越低,材料的耗能能力越弱;Ramberg-Osgood方程能够较好地拟合不同表面变质层厚度的试样在循环加载作用下的骨架曲线;18CrNiMo7-6合金钢的主要组成成分为马氏体,随着表面变质层厚度的增加,位错密度增高;18CrNiMo7-6合金钢基体材料在循环加载作用下表现出循环硬化特征,而随着表面变质层厚度的增加,试样逐渐由没有循环软硬化现象到表现出循环软化特征;Chaboche循环本构模型对不同表面变质层厚度的18CrNiMo7-6合金钢均具有较好的适用性,能准确拟合其在循环加载作用下的力学响应。     

Protection against pulmonary blastomycosis: correlation with cellular and humoral immunity in mice after subcutaneous nonlethal infection

A model of pulmonary blastomycosis in the mouse, in which the portal of entry is the same as natural human infection, was used to study resistance to challenge after subcutaneous infection. One week after subcutaneous infection, mice were partially resistant to pulmonary challenge, and mice challenged two weeks after infection were resistant. Measurement of cellular and humoral immune responses to Blastomyces dermatitidis antigens after subcutaneous infection showed the following. (i) Delayed-type hypersensitivity appeared 1 week after infection, and responses increased for 3 weeks thereafter. (ii) Proliferative responses in vitro appeared in spleen cells at 1 week and in contralateral lymph node cells at 3 weeks, (iii) Serum antibody, detected by an enzyme-linked immunosorbent assay, appeared 1 week after infection and then increased in titer. (iv) Peritoneal macrophages were activated to inhibit replication of B. dermatitidis in vitro by the first week after infection. Prior subcutaneous infection also resulted in rapid clearing of a second subcutaneous challenge, as well as resistance to a lethal intraperitoneal challenge. This resistance was associated with the development of cell-mediated and humoral immune responses. These data provide a chronological framework for selective transfer experiments.     

Systemic and gastrointestinal candidiasis of infant mice as model for antifungal therapy

Systemic and gastrointestinal infection was established in infant (15-19 days old) mice after oral-intragastric challenge with Candida albicans. All survivors retained high levels of organisms in the liver, kidney, spleen, stomach and intestine up to the 24th post infection day. These animals with persistent infections were used to study the efficacy of short term antifungal therapy. Drug treatment was initiated on 13th day for a two week period, treatment with fluconazole was compared with amphotericin B, and 5 fluorocytosine. The results suggest that fluconazole is a useful drug in the treatment of gastrointestinal candidiasis.     

DNA vaccination using expression vectors carrying FIV structural genes induces immune response against feline immunodeficiency virus

Following inactivated virus vaccination trials, the surface glycoprotein gp120 of the feline immunodeficiency virus (FIV) was considered as one of the determinants for protection. However, several vaccination trials using recombinant Env protein or some peptides failed to induce protection. To understand the role of the gp120 protein in vivo, we vaccinated cats with naked DNA coding for FIV structural proteins gp120 and p10. We analyzed the ability of these vaccinations to induce immune protection and to influence the onset of infection. Injection in cat muscles of expression vectors coding for the FIV gp120 protein induced a humoral response. Cats immunized twice with the gp120 gene showed different patterns after challenge. Two cats were, like the control cats, infected from the second week after infection onwards. The two others maintained a low proviral load with no modification of their antibody pattern. The immune response induced by gp120 DNA injection could control the level of viral replication. This protective-like immune response was not correlated to the humoral response. All the cats immunized with the gp120 gene followed by the p10 gene were infected, like the control cats, from the second week but they developed a complete humoral response against viral proteins after challenge. Furthermore, they showed a sudden but transient drop of the proviral load at 4 weeks after infection. Under these conditions, one injection of the p10 gene after one injection of the gp120 gene was not sufficient to stimulate protection. On the contrary, after a period, it seems to facilitate virus replication.     

Pharmacodynamics of vancomycin alone and in combination with gentamicin at various dosing intervals against methicillin-resistant Staphylococcus aureus-infected fibrin-platelet clots in an in vitro infection model

We compared the pharmacodynamic activities of vancomycin with or without gentamicin in an in vitro infection model with methicilin-resistant Staphylococcus aureus-infected fibrin-platelet clots. Infected fibrin-platelet clots (FPCs) were prepared with human cryoprecipitate, human platelets, thrombin, and the organism (approximately 10[9] CFU of MRSA-494/g) and were suspended with monofilament line in an infection model capable of simulating human pharmacokinetics. Antibiotics were bolused to simulate vancomycin regimens of 2 g every 24 h (q24h), 1 g q12h, 500 mg q6h, and continuous infusion (steady-state concentration of 20 microg/ml) and gentamicin regimens of 1.5 mg/kg of body weight q12h and 5 mg/kg once daily (q.d.). Model experiments were performed in duplicate over 72 h. FPCs were removed from the models in quadruplicate at 0, 8, 24, 32, 48, 72 h, weighed, homogenized, diluted, and plated to determine colony counts. The inoculum density at 72 h was used to compare bactericidal activities between the regimens. All regimens containing vancomycin significantly decreased the bacterial inoculum compared to the growth control (P < 0.001). Vancomycin monotherapy regimens were similar in bacterial kill regardless of dosing frequency. The addition of gentamicin (either q12h or q.d.) significantly improved the bactericidal activity of the vancomycin q6h, q12h, and q24h regimens (P < 0.001). The greatest reduction in bacterial density at 72 h (P < 0.001) and the most rapid rate of kill (time to 99.9% killing) were achieved with the regimen consisting of 2 g of vancomycin q24h plus gentamicin (q.d. or q12h).     

Computed tomographic evaluation of comminuted middle phalangeal fractures in the horse

The effect of subinhibitory concentrations of amikacin on Proteus mirabilis motility and adherence to human uroepithelial and to HeLa cells was compared with that of gentamicin. In addition, the effect of both antibiotics on cell surface hydrophobicity was also examined. Exposure of bacterial cells in the logarithmic phase to one fourth of amikacin or gentamicin at one fourth of their respective minimal inhibitory concentrations causes the inhibition of swarming and motility of Proteus strains. Amikacin significantly reduced adhesion of Proteus strains to human uroepithelial cells and gentamicin exerts the same effect to a lesser extent. Such inhibitory concentrations of amikacin or gentamicin had no significant effect on the attachment ability of these strains to HeLa cells compared to the nontreated cells. Treatment of the bacterial cells with amikacin or gentamicin changed significantly the cell surface hydrophobicity towards the hydrophilic state compared to nontreated cells, and it was found to be strain dependent. Since motility and attachment ability are considered as pathogenic traits, these data indicate the impact of amikacin on the virulence factors especially in urinary tract infections with Proteus strains.     

Efficacy of an inactivated vaccine for prevention of reproductive failure induced by porcine reproductive and respiratory syndrome virus

This report describes the results of experiments with an inactivated oily vaccine containing per dose about 10(5.5) median tissue culture infectious dose (TCID50) of the Spanish strain of porcine reproductive and respiratory syndrome (PRRS) virus grown in porcine alveolar macrophages (PAMs). In order to evaluate the efficacy of the vaccine, two experimental infection routes were tested in sows; subsequent intranasal (i.n.) and intravenous (i.v.) (out of a total of 93 piglets born to 7 sows, 16% were mummified, 18.2% were weak and died within 48 h of birth, 37% were stillborn, 5.3% died between 2 and 7 days of age, 22.5% lived for more than one week) and intranasal alone (out of a total of 65 piglets born to 5 sows, 0% were mummified, 22.5% were weak and died within 48 h of birth, 40% were stillborn, 4.6% lived for more than one week). I.N. alone was selected to evaluate the efficacy of the vaccine because this is the natural route of infection. A number of experiments were conducted to test the immunogenicity of the vaccine. In general, after challenge with the homologous strain, protection in vaccinated sows was high (at least 70% of the piglets were born alive and healthy), whereas protection in unvaccinated sows was low (only 10% of the piglets were born alive and healthy). Vaccinated animals devoid of antibodies by immunoperoxidase monolayer assay (IPMA) at the time of challenge were still protected at experimental infection.     

Infectious diseases as a cause and risk factor for cerebrovascular ischemia

Cerebrovascular ischemia can be caused by infectious diseases which involve cerebral arteries or the heart, including infectious endocarditis, bacterial and fungal meningitis, neurosyphilis, neuroborreliosis, herpes zoster, the acquired immunodeficiency syndrome, cat scratch disease and other rare infectious diseases. Presently, there is increasing evidence that infection in general and mainly respiratory infection is a risk factor for ischemic stroke. Case reports and smaller case series reported an association of cerebrovascular ischemia and recent infection in children and younger adults. Two case control studies from Helsinki (54 patients under the age of 50) and from Heidelberg (197 patients aged 80 or less) identified recent infection as an important risk factor for ischemic stroke. Febrile, bacterial and respiratory infections were most important in this respect. In the study from Heidelberg, the neurological deficit was more severe and cardioembolism was more frequent in infection-associated stroke than in stroke without preceding infection. This review summarizes the association of infectious diseases and cerebrovascular ischemia and discusses potential pathogenetic mechanisms linking both diseases.     

Collaborative problem-solving in telemedicine and evidence interpretation in a complex clinical case

The objective of this study was to evaluate the effect of different infection levels of Ostertagia ostertagi and Cooperia oncophora in a simulated 'first grazing season' on the resistance of calves to an artificial challenge infection. The infection levels were determined by the infection schedules and the chemoprophylaxis used. Thirty six 7-11-month old Holstein-Friesian bull calves were randomly divided into four groups. The animals of group B received an ivermectin sustained release bolus (ISRB) on day 0. The calves of group D were treated on days 0 and 56 with a subcutaneous injection of doramectin (0.2 mg kg(-1) BW). Group C was the untreated control group. The calves of group N were used as helminth-naive controls, while the animals of groups B, C and D were trickle infected for 24 weeks. The infection schedules were designed to simulate the expected infection pattern for each treatment group under set-stocked conditions in temperate climate areas. After the last infection, all animals were treated with oxfendazole. One week later, all animals received a challenge infection of 50,000 O. ostertagi L3 and 100,000 C. oncophora L3, spread over 10 consecutive days. During the primary infection period the faecal egg output and the serum pepsinogen and antibody levels reflected the different levels of host-parasite contact between the groups (group C > group D > group B > group N). After the challenge infection, faecal egg counts, total Ostertagia burden, size of the adult worms and abomasal globule leucocyte counts all indicated a positive relationship between the level of Ostertagia infection during the primary infection period and the level of acquired resistance. A reduction of host-parasite contact during the primary infection period, as a consequence of the infection schedule and the chemoprophylaxis used, resulted in a diminished level of resistance to the artificial challenge infection with O. ostertagi. Faecal cultures and small intestine worm counts indicated that all previously infected groups had acquired a high degree of resistance to the Cooperia challenge infection.     

Pharmacokinetic properties of gentamicin and amikacin in the cockatiel

Gentamicin and amikacin are commonly used in veterinary medicine to treat a variety of gram-negative bacterial infections. The present study evaluates the pharmacokinetics of gentamicin sulfate and amikacin sulfate in the cockatiel (Nymphicus hollandicus), a small (approximate body weight = 100 g) psittacine bird, utilizing treatment regimens developed in larger parrot species. Serum antibiotic concentrations were determined in cockatiels following twice-daily intramuscular treatment with 5 mg gentamicin/kg body weight and 15 mg amikacin/kg body weight. In the present study, peak values of gentamicin were 4.6 +/- 1.45 micrograms/ml, and trough values were 0.17 +/- 0.04 micrograms/ml. Amikacin administration resulted in peak values of 27.3 +/- 6.9 micrograms/ml and trough concentrations of 0.9 +/- 0.3 micrograms/ml. Based on the present study, an appropriate intramuscular dose regimen for gentamicin in cockatiels is 5 to 10 mg/kg body weight either two or three times per day. An intramuscular amikacin dosage of 15 to 20 mg/kg body weight either two or three times per day is recommended for treatment of infections caused by susceptible bacteria.     

A new method for in vivo evaluation of biofilms on surface-modified silicone rubber voice prostheses

A new method is presented that permits a rapid and accurate in vivo evaluation of biofilm formation on surface-modified silicone rubber voice prostheses. The method is based on partial modification of a Groningen button voice prosthesis by exposing half of the prosthesis to an argon plasma. This results in one side of the prosthesis becoming hydrophilic while leaving the unmodified side hydrophobic as a control. Modified prostheses were placed in patients for an evaluation period of approximately 4 weeks. Despite making the silicone rubber surface hydrophilic, biofilm formation was stimulated when compared to unmodified, hydrophobic silicone rubber. Findings show that biofilm formation on voice prostheses is influenced by hydrophobicity of a silicone rubber surface. The method of partial surface modification used was seen to be suitable for demonstrating such influences regardless of nutrition and other variations in the patient's lifestyle. Microbiological analysis of the biofilms on both sides of the prosthesis valve did not show any changes in microbial composition, with Candida albicans, streptococci and staphylococci being the most commonly isolated strains.     

Prevention of biofilm formation by polymer modification

Bacterial biofilm formation on synthetic polymers plays an important role in industry and in modern medicine, leading, for example, to difficult-to-treat infections caused by colonized foreign bodies. Prevention of biofilm formation is a necessary step in the successful prophylaxis of such infections. One approach is to inhibit bacterial adherence by polymer surface modification. We have investigated polymer modification by glow discharge treatment in order to study the influence of the modified surface on bacterial adherence. Surface roughness, surface charge density and contact angles of the modified polymers were determined and related to the adherence of Staphylococcus epidermidis KH6. Although no influence of surface roughness and charge density on bacterial adherence was noticed, a correlation between the free enthalpy of adhesion (estimated from contact angle measurements) and adherence was observed. There seems to exist a certain minimum bacterial adherence, independent of the nature of the polymer surface. Modified polymers with negative surface charge allow for bacterial adherence close to the adherence minimum. These polymers could be improved further by the ionic bonding of silver ions to the surface. Such antimicrobial polymers are able to prevent bacterial colonization, which is a prerequisite for biofilm formation. It is suggested that modification of polymers and subsequent surface coupling of antimicrobials might be an effective approach for the prevention of bacterial biofilm formation.     

Experience with once daily dosing of gentamicin: considerations regarding dosing and monitoring

Plasma concentrations of gentamicin following a fixed dose of 240 mg once daily to patients with normal renal function were measured. The purpose was to establish guidelines to achieve a sufficiently high peak concentration with an appropriately low risk of accumulation. In 40 patients, 1-hour concentrations of plasma gentamicin had a median of 9.3 mg/l (range: 4.5-19.0 mg/l) and 9.7 mg/l (range: 3.6-14.6 mg/l) on days 1 and 3 of gentamicin treatment, respectively. Thirty-nine patients had 1-hour concentrations > 5 mg/l. The 1-hour concentrations varied considerably intra- and interindividually but showed a significant inverse correlation with body weight, surface area and the estimated endogenous creatinine clearance. The plasma gentamicin elimination half-life correlated significantly with age and inversely with body weight and creatinine clearance. There was no increase in the mean plasma creatinine from day 0 to day 4. No patients showed signs of nephrotoxicity, although 2 patients, both elderly and with low body weight, showed signs of beginning gentamicin accumulation. In conclusion, gentamicin treatment with the dose of 240 mg once daily in 3 days to adults with normal kidney function generally does not require adjustment or monitoring. However, the dose should be increased in young patients with an excessive body weight, and decreased doses are needed for old and underweight patients. Monitoring of trough plasma gentamicin concentration is not necessary with treatment duration of 3 days or less.