Efficacy Of Antimicrobial Agents Research Articles

Assessment of Clinical Antimicrobial Garenoxacin (GRNX) Efficacy Using Clinical Scoring in Adults with Acute Rhinosinusitis

In a prospective study of rhinosinusitis treatment efficacy in 163 subjects at 30 medical facilities between 2008 and 2009, we studied isolation of three major pathogenic bacteria-Streptococcus pneumoniae, Haemophillus influenzae, and Moraxella catarrhalis. We also examined clinical garenoxacin (GRNX) efficacy in 106 acute rhinosinusitis cases and 57 acute chronic rhinosinusitis exacerbation cases using Japan Acute Rhinosinusitis Clinical Guideline 2010 clinical scoring. Isolation of S. pneumoniae was 50.0% (22/44), H. influenzae 43.2% (19/44), and M. catarrhalis 6.8% (3/44) in 106 acute rhinosinusitis subjects. Drug-resistant strains accounted for over 50% in S. pneumoniae and H. influenzae. Isolation of the three bacterial pathogens in 57 acute chronic rhinosinusitis exacerbation subjects was 50.0% (9/18) in S. pneumoniae, 27.8% (5/18) in H. influenzae, and 22.2% (4/18) in M. catarrhalis. Drug resistance exceeded 40% in S. pneumoniae and H. influenzae. In efficacy studies of 97 subjects, GRNX at 400 mg/day in 54 with acute rhinosinusitis was 100%—marked improvement in 51.9% (28/54) and moderate in 48.1% (26/54). Efficacy in 43 acute chronic rhinosinusitis exacerbation subjects was 95.3%—marked improvement in 79.1% (34/43) and moderate in 16.3% (7/43). These results show the usefulness of clinical scoring in diagnosing diseases severity and in studying the efficacy of antimicrobial agents. Data clearly indicated the high clinical and bacterial efficacy of garenoxacin in treating adult rhinosinusitis.

Topical treatment of Klebsiella pneumoniae B5055 induced burn wound infection in mice using natural products

Burn wound infection remains the principal cause of death in burn patients. Efficacy of honey and aloe vera gel was evaluated in the treatment of burn wound infection induced with Klebsiella pneumoniae B5055 and their efficacy was compared with an isolated and well-characterized Klebsiella specific phage Kpn5. A full thickness burn wound was induced in mice and infected with K. pneumoniae B5055 via topical route. The efficacy of natural antimicrobial agents (honey and aloe vera gel) topically applied daily was compared with the efficacy of phage Kpn5 suspended in hydrogel applied topically a single time on the burn wound. Efficacy of these antimicrobial agents was assessed on the basis of the percentage of infected mice that survived following treatment. In comparison to untreated control mice, those treated with a single dose of phage Kpn5 at MOI of 200 showed significant reduction in mortality (P < 0.001). Daily application of honey and aloe vera gel provided significant protection (P < 0.001), but in combination with phage, no additional advantage was observed (P > 0.05) compared to the use of honey and aloe vera gel alone. The results of this study strongly suggest that phage Kpn5 has therapeutic value in treating burn wound infection in mice as a single topical application of this phage was able to rescue mice from infection caused by K. pneumoniae B5055 in comparison to multiple applications of honey and aloe vera gel.

A Laboratory Model Biofilm Fermenter: Design and Initial Trial on a Single Species Biofilm

The minimum inhibitory concentration (MIC) does not provide information on the efficacy of antimicrobial agents against infections involving biofilms, which are many times more resistant than planktonic forms of bacteria. This report is on the design and initial trial of a device for growing standard biofilms and testing antimicrobial agents. We constructed a durable, autoclaveable laboratory model biofilm fermenter (LMBF) that holds hydroxyapatite discs 300 microm below a surface onto which an artificial saliva medium drips at a rate comparable to human salivary flow. Inoculated with Streptococcus sanguinis, the device formed biofilms that were swept with a Teflon wiper under aerobic conditions. Five-day-old biofilm-coated discs were aseptically removed and placed in 3 ml of sterile saline, 0.12% chlorhexidine gluconate, or 0.1% phosphate-buffered chlorine dioxide mouthwash for 1 minute. The discs and test agent were immediately diluted with saline to 10 ml, vortexed for 30 seconds, serially diluted, plated on blood agar, and incubated anaerobically 2 days. Bacterial counts were done, and the MIC of each mouthwash was determined. In tests with sterile water and sterile medium, the device maintained a closed system. After inoculation with S. sanguinis, a steady state was reached at day 5. Chlorhexidine at stock concentration achieved about a 2 log10 reduction (P = 0.002), but never achieved complete killing. Chlorine dioxide had no significant effect. The MIC against planktonic S. sanguinis was 112.8 microg/ml for chlorhexidine and 9.0 microg/ml for chlorine dioxide. The LMBF generates and maintains a single-species oral model biofilm to a steady state and enables in vitro tests of disinfectant mouthwashes in simulated clinical use. It should be usable for more advanced tests of multiple species biofilms.

Natural Antimicrobial Susceptibility Patterns of Kluyvera ascorbata and Kluyvera cryocrescens Strains and Review of the Clinical Efficacy of Antimicrobial Agents Used for the Treatment of Kluyvera Infections

The natural susceptibility of 58 K. ascorbata and 24 K. cryocrescens strains to 71 antimicrobial agents was investigated. MIC values were determined with a microdilution procedure in cation-adjusted Mueller Hinton broth (for all strains) and IsoSensitest broth (for some strains). Both species were naturally sensitive or of intermediate susceptibility to tetracyclines, aminoglycosides, quinolones, antifolates, chloramphenicol, nitrofurantoin, fosfomycin, aminopenicillins plus β-lactamase inhibitors, acylureidopenicillins, carbapenems, aztreonam and some cephalosporins. Uniform natural resistance was found with several macrolides, lincosamides, streptogramins, glycopeptides, rifampicin, fusidic acid, linezolid, penicillin G, oxacillin, and amoxicillin. To the latter agent, some strains of both species were also of intermediate susceptibility. Species-related differences in natural susceptibility affecting clinical assessment criteria were seen with azithromycin, cethromycin, telithromycin, ticarcillin and some cephalosporins, to which K. ascorbata was less susceptible than K. cryocrescens. Medium-related differences in susceptibility were restricted to a few antibiotics.A data base about the natural susceptibility of the two most common Kluyvera spp. to a wide range of antimicrobial agents is presented. It can be used for the validation of forthcoming susceptibility trials of these microorganisms. Although some susceptibilty patterns might be helpful for the phenotypical separation of K. ascorbata from K. cryocrescens, they do not allow a separation of these species. The literature dealing with the clinical efficacy of antimicrobial agents used for the treatment of Kluyvera infections is discussed.

Use of pharmacodynamic indices to predict efficacy of combination therapy in vivo.

Although combination therapy with antimicrobial agents is often used, no available method explains or predicts the efficacies of these combinations satisfactorily. Since the efficacies of antimicrobial agents can be described by pharmacodynamic indices (PDIs), such as area under the concentration-time curve (AUC), peak level, and the time that the concentration is above the MIC (time>MIC), it was hypothesized that the same PDIs would be valid in explaining efficacy during combination therapy. Twenty-four-hour efficacy data (numbers of CFU) for Pseudomonas aeruginosa in a neutropenic mouse thigh model were determined for various combination regimens: ticarcillin-tobramycin (n = 41 different regimens), ceftazidime-netilmicin (n = 60), ciprofloxacin-ceftazidime (n = 59), netilmicin-ciprofloxacin (n = 38) and for each of these agents given singly. Multiple regression analysis was used to determine the importance of various PDIs (time>MIC, time>0.25 x the MIC, time>4 x the MIC, peak level, AUC, AUC/MIC, and their logarithmically transformed values) during monotherapy and combination therapy. The PDIs that best explained the efficacies of single-agent regimens were time>0.25 x the MIC for beta-lactams and log AUC/MIC for ciprofloxacin and the aminoglycosides. For the combination regimens, regression analysis showed that efficacy could best be explained by the combination of the two PDIs that each best explained the response for the respective agents given singly. A regression model for the efficacy of combination therapy was developed by use of a linear combination of the regression models of the PDI with the highest R(2) for each agent given singly. The model values for the single-agent therapies were then used in that equation, and the predicted values that were obtained were compared with the experimental values. The responses of the combination regimens could best be predicted by the sum of the responses of the single-agent regimens as functions of their respective PDIs (e.g., time>0.25 x the MIC for ticarcillin and log AUC/MIC for tobramycin). The relationship between the predicted response and the observed response for the combination regimens may be useful for determination of the presence of synergism. We conclude that the PDIs for the individual drugs used in this study are class dependent and predictive of outcome not only when the drugs are given as single agents but also when they are given in combination. When given in combination, there appears to be a degree of synergism independent of the dosing regimen applied.

Comparative efficacies of antimicrobial agents against clarithromycin-resistant Helicobacter pylori

Comparative efficacies of antimicrobial agents against clarithromycin-resistant Helicobacter pylori

Preliminary Report,on DU-6859a for Urinary Tract Infection

The efficacy safety, and clinical value of DU-6859a, a novel new quinolone antimicrobial, were evaluated in a multicenter study. The subjects were selected from among patients aged 20 to 79 years with mild to moderate uncomplicated or complicated urinary tract infection (UTI). DU-6859a was administered orally after meals at a dose of 50–100 mg once or twice daily for 3–7 days. The clinical efficacy rate for all target infections was determined to be 88.5%, (100/113) by the attending physicians. The efficacy rate was 100% (21/21) for acute uncomplicated cystitis, 84.9% (62/73) for complicated cystitis, and 88.9% (16/18) for complicated pyelonephritis. The overall clinical efficacy rate and the eradication rate for urinary pathogens were determined according to the Criteria for Evaluation of Clinical Efficacy of Antimicrobial Agents for UTI proposed by the Japanese UTI Committee. The rates were, respectively, 100% (9/9) and 100% (11/11) for acute uncomplicated UTI and 88.0% (66/75) and 91.2% (93/102) for complicated UTI. Clinical adverse reactions were experienced in seven (5/7%) out of 123 evaluable patients, but all symptoms were mild. Laboratory adverse reactions, such as slight elevations of GOT and/or GPT, were noted in 13 (12.1%) out of 107 evaluable patients. DU-6859a showed excellent clinical efficacy against acute uncomplicated and complicated UTI which reflected its high antibacterial activity in vitro and did not cause any clinically significant adverse reactions. These results show that DU-6859a is worthy of further clinical studies for the treatment of UTI.

A Quantitative Bacterial Plaque Assay for the Enumeration of Viable Acanthamoeba Cells

The quantitation of the efficacy of antimicrobial agents against Acanthamoeba requires the use of accurate and reliable quantitative methods. In the literature, data obtained by different methods conflict. Previous studies assessed efficacy against Acanthamoeba with several different methods: minimal inhibition of mobility after 6 hours of exposure [1]; simple presence or absence of motile trophozoites after 4 hours of contact [2]; number of cells per milliliter during 140 hours of growth in culture (method of cell count not given) [3]; hemocytometer counts of cells after 4, 24, and 72 hours of chemical contact [4]; and filtration of challenged solutions followed by culture for motile trophozoites after 24 hours of chemical contact [5]. Quantitative rates for the killing of Acanthamoeba cells are difficult to calculate from these methods because the number of viable cells

Antimicrobial Resistance: The Never Ending Story

This article has no abstract.

A mouse model for simultaneous pharmacokinetic and efficacy studies of antibiotics at sites of infection.

Tissue penetration may be an important pharmacokinetic determinant to achieve the chemotherapeutic efficacy of antimicrobial agents. We describe a mouse model for the simultaneous study of antibiotic kinetics and efficacy at the site of infection. With the doses tested there was no difference in drug penetration into healthy tissue and tissue at the site of acute bacterial infection. Ampicillin and netilmicin levels over the minimal inhibitory concentration (MIC) were needed to produce significant bacterial killing. During the 6 h observation period susceptible Gram-positive bacteria were eradicated whereas Gram-negative bacteria were reduced in number but not eradicated, even though the antibiotic concentrations exceeded minimal bactericidal concentration (MBC) three times.

Inhibition of Legionella pneumophila multiplication within human macrophages by antimicrobial agents.

The activity of serial concentrations of different antimicrobial agents on the multiplication of Legionella pneumophila within human monocyte-derived macrophages was studied. The results led to the definition of a minimal extracellular concentration inhibiting intracellular multiplication (MIEC). According to the MIECs, the antimicrobial agents tested were classified in three groups: very active (MIEC less than or equal to 0.06 microgram/ml), such as erythromycin, rifampin, and pefloxacin; active (1 microgram/ml greater than or equal to MIEC greater than or equal to 0.1 microgram/ml), such as sulfamethoxazole-trimethoprim or doxycycline; and ineffective, such as cefoxitin, which was not active within macrophages at as high as 64 micrograms/ml despite a low MIC (0.2 microgram/ml) on bacterial charcoal-yeast extract agar. The activity of netilmicin was difficult to assess because of its effect on extracellular legionellae. Combinations of erythromycin with rifampin and pefloxacin with erythromycin, rifampin, doxycycline, or netilmicin showed an additive effect and no antagonism. These results obtained in a cellular model are in agreement with the efficacy of antimicrobial agents in experimental infections and in Legionnaires disease. They sustain clinical interest in the new quinolones, such as pefloxacin, and in combinations of antimicrobial agents for the treatment of Legionnaires disease.

An overview: evaluation of cefonicid in infections of the urinary tract, lower respiratory tract, and skin and soft tissue.

Infections of the urinary and lower respiratory tracts and of skin and soft tissue constitute a large proportion of infections requiring antimicrobial therapy. For many antimicrobial agents, one dose will cure lower urinary tract infection. In contrast, relapse of upper tract infection is common even after two weeks of treatment. In comparing the efficacy of antimicrobial agents in urinary infection, it is critical that patients assigned to different agents be equivalent. The questions about cefonicid in urinary infection that must be addressed concern (1) adverse effects and tolerability, (2) cost, and (3) rationale for the use of a parenteral preparation in uncomplicated urinary infection. In lower respiratory tract infections, therapeutic efficacy is difficult to evaluate primarily because of the difficulty in determining the causative role of the organisms isolated from sputum. The inclusion of information from gram-stained preparations reduces the diagnostic error. As far as cefonicid in treatment of pneumonia is concerned, the high serum protein binding reported and the relatively high minimal inhibitory concentrations for gram-positive cocci must be addressed. In skin and soft-tissue infections, therapeutic efficacy is difficult to evaluate because of the lack of isolates and the self-limited nature of many cutaneous infections.

Theory and applications of pulse dosing: a summary of the symposium.

Since the dawn of the antibiotic era, questions have existed about proper dosing of these drugs, including the amount needed, the proper interval between doses, and the duration of therapy. The goals of this symposium were to explore the effect of one of these factors, the interval between doses, on the efficacy of antimicrobial agents and to examine the relative merits of intermittent (pulse) and continous adminstration from both the theoretical and practical standpoints. This symposium provided an opportunity for experts from around the world to gather and discuss data relative to this important subject. To a large extent many of the early questions about dosing remain unanswered. Since most early antibiotics were of limited spectrum and of relatively low toxicity, some of the important conse

Shigellosis. To treat or not to treat?

OPINIONS differ on the most appropriate course of therapy for shigellosis because of conflicting evidence in the literature concerning the efficacy and possible hazards of specific antibiotic therapy. Proponents of specific chemotherapy note that the efficacy of antimicrobial agents in shigellosis is well established. 1 Moreover, several studies have shown that antibiotics will notably decrease the excretion of shigellae in the stools and abbreviate the clinical course of both mild and severe disease. 2,3 Those opposed to specific therapy except in certain special cases argue that the disease is self-limited and usually mild, that strains have repeatedly emerged resistant to whatever antibiotic happened to be in vogue at the time, and that this resistance has frequently been R factor-mediated, resulting in organisms resistant to multiple antibiotics. These viewpoints have recently been summarized. 4 The clinician responsible for deciding whether to prescribe or withhold antimicrobial therapy in an individual case