A super-infection in the cornea caused by Stemphylium, Acremonium, and α-Streptococcus.

BACKGROUND: Polymicrobial keratitis with fungus and bacteria can lead to blindness and is challenging to treat. Here, we introduce a case of fungal keratitis caused by two different strains in addition to definite bacterial super-infection caused by an α-Streptococcus sp., and describe the importance of microscopic examination. CASE PRESENTATION: A 74-year-old woman, who had a past history of infection with leprosy, presented with conjunctival hyperaemia, pain, and corneal opacity in her right eye. Under the presumptive diagnosis of infectious keratitis, corneal scrapings were stained by various reagents and inoculated on several agar plates. Microscopic findings of the scrapings revealed fungi and a small number of Gram-positive cocci. Multiple anti-fungal therapies with levofloxacin ophthalmic solution were administered. Although empiric treatment was initially effective, keratitis recurred 10 days after its initiation. Repeated corneal scraping revealed an abundance of Gram-positive chain cocci and a small amount of fungi, resulting in the switching of an antibiotic medication from levofloxacin to moxifloxacin and cefmenoxime. Keratitis resolved gradually after the conversion. Stemphylium sp., Acremonium sp., and α-Streptococcus sp. were simultaneously isolated from the corneal scrapings. CONCLUSIONS: To the best of our knowledge, this is the first case of fungal keratitis caused by Stemphylium sp., and also the first case of super-infection in the cornea caused by two different fungi and one bacterium. Microscopic examination of the corneal scrapings was beneficial in rapid decision of changing to appropriate drug according to the dominancy of pathogenicity.

Clinical Characteristics and Bacteriological Profile of Moraxella Keratitis.

PURPOSE: Moraxella species are rare causative pathogens of severe sight-threatening keratitis. The aim of this study was to analyze the clinical presentation, predisposing risk factors, in vitro antimicrobial susceptibility, and treatment associated with Moraxella keratitis. METHODS: We retrospectively reviewed 30 culture-proven cases of Moraxella keratitis from multiple centers in Japan. RESULTS: The mean age of the patients was 58.4 ± 23.4 years. The most common ocular conditions were contact lens wearing (5 patients, 16.7%) and trauma (3 patients, 10.0%). Seven patients had diabetes mellitus. Sixteen patients exhibited hypopyon in association with the corneal focus. Ring-shaped infiltration was found in 9 patients (30.0%), and irregular or amoebic-shaped infiltration was observed in 13 patients (43.3%). Eight patients (26.7%) showed small round infiltrates. All Moraxella isolates were sensitive to fluoroquinolones and aminoglycosides. All were treated with a combination ophthalmic solution containing a fluoroquinolone, tobramycin, and cefmenoxime. Although no patients developed corneal perforation, the response to treatment was slow in all cases; the mean treatment period was 41.9 days. CONCLUSIONS: In Japan, Moraxella keratitis occurs in patients with contact lens wear, trauma, and diabetes mellitus. It presents as a small, round, ring-shaped, irregularly shaped, or amoebic-shaped focus. Moraxella species exhibit good susceptibility to fluoroquinolones and aminoglycosides. Because the treatment response may be very slow, these agents should be continued for a long period of time.

Characteristics of Pseudomonas corneal infection related to orthokeratology.

PURPOSE: To describe a Pseudomonas aeruginosa corneal infection resulting from orthokeratology. METHODS: Case report. RESULTS: A 17-year-old boy wearing orthokeratology (OK) lenses was referred to our clinic because of redness in his right eye in spite of his usage of ofloxacin (OFLX) eye drops. An excavated paracentral corneal ulcer with an immune ring and hypopyon was observed. It was positioned under the paracentral steeper portion of the optic of the OK lens. Culture of the lens solution revealed P. aeruginosa. The patient was treated with topical OFLX and cefmenoxime (CMX) plus intravenous and subconjunctival injections of cefozopran (CZOP), successfully. The antibiotic susceptibility of P. aeruginosa by the disk diffusion susceptibility test was reduced under moderately hypoxic conditions. Glycocalyx slime was formed on the OK lens in vitro by P. aeruginosa isolated from the case. CONCLUSIONS: Changes in P. aeruginosa susceptibility to antibiotics under moderately hypoxic conditions and glycocalyx slime formation might affect the features of OK lens-associated infections.

Comparative clinical study of cefcapene pivoxil and cefteram pivoxil in chronic respiratory tract infections by a double-blind method.

In a double-blind study, the efficacy and safety of the novel cephem antibiotic cefcapene pivoxil (CFPN-PI; 450 mg/day) was compared with cefteram pivoxil (CFTM-PI; 600 mg/day) in 171 patients with chronic respiratory tract infections. There was no significant difference between the clinical efficacy of the two drugs (80.2% for CFPN-PI versus 78.9% for CFTM-PI). There was no significant difference in the rate of elimination of the causative bacteria (60.5% for CFPN-PI versus 65.9% for CFTM-PI). Side-effects were observed in 6.0% of patients treated with CFPN-PI compared with 6.4% of patients treated with CFTM-PI. There were no significant differences in incidence of abnormal laboratory findings following treatment with the two drugs (13.9% for each), and none of the side-effects was severe. We conclude that CFPN-PI (450 mg/day) was as effective and as well tolerated as CFTM-PI (600 mg/day) in the treatment of chronic respiratory tract infections.

Evaluation of oral antimicrobial agent levels in tooth extraction sites.

OBJECTIVE: The purpose of this study was to evaluate various oral antimicrobial agent levels in tooth extraction sites. STUDY DESIGN: The concentration of dental alveolar blood in extraction wounds after the oral administration of talampicillin (500 mg), cefaclor (500 mg), cefteram pivoxil (200 mg), cefuroxime axetil (250 mg), cefdinir (200 mg), and ofloxacin (100 mg) was determined in 338 patients and was assessed on the basis of its antimicrobial activity against Streptococcus isolated in odontogenic infections. RESULTS: The percentage of patients whose concentrations exceeded the minimum inhibitory concentration for 90% of Streptococcus was 62.5% to 100% for talampicillin at 30 to 360 minutes, 0% to 12.5% for cefaclor at 30 to 360 minutes, 18.2% to 100% for cefteram pivoxil at 30 to 480 minutes, 50% to 100% for cefuroxime axetil at 30 to 480 minutes, 0% to 50% for cefdinir at 16 to 290 minutes, and 0% to 40% for ofloxacin at 30 to 480 minutes. CONCLUSION: These results indicate that talampicillin, cefteram pivoxil, and cefuroxime axetil have minimum inhibitory concentration levels for 90% of Streptococcus in tooth sockets.

Failure of pre-diarrheal antibiotics to prevent hemolytic uremic syndrome in serologically proven Escherichia coli O157:H7 gastrointestinal infection.

A girl had hemolytic uremic syndrome after Escherichia coli O157:H7 infection, despite pre-diarrheal administration of an antibiotic that prevented detectable intestinal colonization. This report casts doubt on the advisability of antibiotic therapy for E coli O157:H7 infections and has implications for our understanding of the mechanism of this disorder.

Modeling the response of pneumonia to antimicrobial therapy.

The response to antimicrobial therapy in patients with pneumonia was assessed by using a previously developed pneumonia scoring system. Patients from two different clinical trials were evaluated. The first group (n = 22) was treated with cefmenoxime. For these patients, doses were adjusted to achieve an area under the plasma concentration-versus-time curve (AUC) above the MIC of 140 microg x h/ml and pneumonia response scores were evaluated retrospectively. The second group (n = 21) were treated with either ciprofloxacin (CIP) or ceftazidime (TAZ) in a randomized clinical trial. Here, doses were adjusted to achieve AUC from 0 to 24 h/MIC values that were > 250 SIT(-1) x h (estimate of the area under the curve of inverse serum inhibitory titer versus time) and pneumonia response scoring was concurrent. In both studies eradication of the pathogen was determined by serial endotracheal cultures and clinical parameters were scored daily. A decrease in total score was indicative of an improving clinical condition. The percent change in clinical daily score was determined for each day of treatment. The rate of clinical response was determined by linear regression of the percent change in daily clinical score versus time during the course of antimicrobial therapy. Factors predictive of time to eradication were explored by interval analysis. Logistic regression was used to determine the earliest time point in therapy at which treatment scores predicted outcome. Kruskal-Wallis analysis of variance was used for statistical analysis, and significance was accepted at P < 0.05. There were no differences in baseline scores at day one for the patients treated with different antibiotics (P = 0.58). For patients with pathogen eradication, a significant difference between the two studies in time to eradication was found: 4.8 days for cefmenoxime-treated patients and 1.4 days for CIP- or TAZ-treated patients (P < 0.001). For patients experiencing bacterial eradication, the rates of clinical change for cefmenoxime and CIP or TAZ treatment were similar (P = 0.77). For patients with organisms that were not eradicated, the rates of change were similar (P = 0.14). There was a significant difference in the rate of change for patients experiencing eradication compared with that for patients in which the organism persisted (P << 0.01). Both treatment group and rate were found to be predictive of days to eradication. There was a significant difference in the percent change in clinical score on day 3 of therapy for patients with bacteria that were eradicated versus those with persistent organisms (P < 0.01). The percent change was more predictive of outcome with each subsequent day. Patients who demonstrated a > or = 10% reduction in clinical score after 72 h of treatment had an 88% probability of bacterial eradication. The clinical scoring system is a useful tool for modeling the response of pneumonia to antimicrobial therapy. The ability to predict outcome relatively early in therapy, by using a scoring system of clinical parameters which can be routinely monitored, will aid in assessing the response to antimicrobial therapy in clinical as well as in research settings.

[A randomized control study on the treatment of 123 cases of bacterial infections with cefteram and cefaclor].

To evaluate the efficacy and the safety of cefteram in bacterial infections, a randomized control study of cefteram and cefaclor on the treatment of 123 patients with respiratory and urinary tract infections was carried out. The result showed that the effective and bacterial eradication rates were 92.1% and 91.4% for cefteram. 83.3% and 85.2% for cefalor. Adverse reactions were mainly gastrointestinal reactions, occurring in 4.6% of the cefteram group and 9.4% of the cefaclor group. Study of minimum inhibitory concentration displayed high antibacterial activity of cefteram for enterobacteriaceae and other Gram-negative organisms and its activity was higher than that of gentamyicin and ciprofloxacin for E. coli. It is concluded that cefteram was effective and safe in the treatment of respiratory and urinary tract infections.

Mathematical examination of dual individualization principles. (III): Development of a scoring system for pneumonia staging and quantitation of response to antibiotics: results in cefmenoxime-treated patients.

OBJECTIVE: In order to quantitatively express the important, time-related aspects of response to antimicrobial therapy in patients with pneumonia, we required validated measures of the time course of events during the infection. To quantitate the changes in clinical status in relation to changes in cultures, we developed a scoring system to be used for patient assessment during therapy. DESIGN: Retrospective data collection, prospective analysis of factors. SETTING: Intensive care unit, Millard Fillmore Hospital. PATIENTS: Twenty-eight patients with nosocomial pneumonia. MAIN OUTCOME MEASURES: Clinical parameters were assessed daily for the duration of antimicrobial therapy. Using linear regression, the rate of clinical change in each patient treated was quantified. Eradication of the pathogen was determined by serial cultures of the infection site. RESULTS: Seventeen of the patients demonstrated eradication of the organism, and 11 demonstrated persistence of the pathogen (7 were considered colonization). The system described the patients at baseline in that the mean baseline scores were similar in both groups of patients (p = 0.79). Patients in whom the pathogen was eradicated showed a rate of clinical improvement significantly different from those who had persistence of the organism (p = 0.04). In patients demonstrating eradication, the time to eradication inversely correlated with the rate of clinical improvement (p < 0.05). Of the ten parameters descriptive of the disease, those most sensitive to change after eradication of bacteria were body temperature, bacterial Gram stain, white blood cell Gram stain, and volume of sputum. CONCLUSIONS: In this set of pneumonia patients, the scoring system effectively quantified both baseline and time-related changes in clinical status. The system distinguished between the clinical course of the patient with organism eradication versus organism persistence. A shorter time to eradication was associated with a better clinical response. Prospective study of the system will determine its sensitivity.

Levels of cefmenoxime in sera and peritoneal tissues of patients undergoing gastrointestinal surgery.

It is not known whether a prophylactic antibiotic administered prior to surgery reaches adequate levels in the peritoneum, where peritonitis may take place. This study determined levels of cefmenoxime in sera and peritoneal tissues of patients undergoing gastrointestinal surgery. Fifteen patients who underwent elective gastrointestinal surgery received an intravenous drip infusion of cefmenoxime (2 g) over 1 h prior to surgery. In patients who underwent gastrectomy, the level of cefmenoxime in serum was 130.8 +/- 6.9 micrograms/ml at laparatomy and decreased to 5.0 +/- 0.7 micrograms/ml at 4 h. Levels in parietal peritoneal and omental tissues at laparotomy were 35.3 +/- 5.2 and 19.2 +/- 3.5 micrograms, respectively, and decreased time dependently. In patients who underwent cholecystectomy, the level of cefmenoxime in serum was 137.9 +/- 7.3 micrograms/ml at laparotomy and decreased to 5.0 +/- 1.2 micrograms/ml at 4 h. Levels in parietal peritoneal and omental tissues were 31.0 +/- 8.4 and 13.7 +/- 3.3 micrograms/g, respectively, and decreased time dependently. The level of cefmenoxime in serum correlated with the levels of cefmenoxime in parietal peritoneum (r = 0.64, P less than 0.01) and in omentum (r = 0.47, P less than 0.02). In patients with appendicitis who received a bolus injection of 2 g of cefmenoxime, the level of drug in inflammatory omental tissue correlated with the level in serum. The levels in peritoneal tissue during surgery lasting up to 2 h were significantly greater than in MIC of cefmenoxime against almost all bacteria reported. A preoperative single dose of 2 g of cefmenoxime probably is effective as a prophylactic for intraoperative contamination.

[Identification and antibiotic prophylaxis of high-risk patients in biliary tract surgery].

A prospective randomized trial has compared 3 policies of antibiotic prophylaxis in biliary surgery. Patients considered to be high-risked against postoperative infection were randomly allocated to 2 groups: in group CTM-H, patients were given cefotiam; in group CMX-H, patients were given cefmenoxime. Patients free of risk factors (group CTM-L) were all given cefotiam. The high-risk factors adopted in this trial were; emergency surgery, presence of jaundice or cirrhosis, malignant disease, diabetes mellitus, age over 70, recent biliary tract infection, choledocholithiasis, and previous biliary surgery. Postoperative infection occurred in 2.1% (4/190) in the CTM-L group, which was lower compared to 15.5% (11/71) of the CMT-H group (p less than 0.01), and 11.3% (8/71) of the CTM-H group (p less than 0.01). The rates of bacterial isolation from intraoperative bile culture and wound swab were significantly high in the two high-risk groups compared to the low-risk group, but is was not different within the two high-risk groups. These findings suggest that while cefotiam is appropriate for prophylaxis for the low-risk patients, the utmost care should be taken in the high-risk patients to prevent intraoperative contamination along with prophylactic antibiotic therapy which covers the bacteria isolated from the bile.

Synergistic effects of romurtide and cefmenoxime against experimental Klebsiella pneumonia in mice.

We investigated the synergistic effects of romurtide (MDP-Lys [L18]) and cefmenoxime (CMX) in the treatment of experimental Klebsiella pneumonia in mice. Mice were infected with 1 x 10(4) CFU of Klebsiella pneumoniae by inhalation of aerosol bacterial suspension. About 90% of untreated animals died within a week; however, the mortality rate of animals treated with CMX alone at a dose of 40 mg/kg/day was 60% at 7 days after the infection. When one or two doses of L18 were administered before or after the infection concomitantly with CMX, a remarkable improvement in the survival rate was observed. There was no significant improvement in the survival rate of animals treated with L18 alone before or after infection. Histopathological sections of the lungs of mice treated with CMX and L18 showed slower progression of infection than those of mice treated with CMX alone. Significant differences were also found in quantitative cultures of viable bacteria in the lungs 1 to 4 days after the infection. Although viable bacterial counts in the lungs of the control and CMX-treated groups showed a rapid increase 24 to 48 h after the infection, they remained lower than the initial counts (x 10(4)) in the lungs of mice treated with combination regimens. From these results, it can be concluded that L18 is a useful biological response modifier in the treatment of acute pulmonary bacterial infections.

Diffusion of cefmenoxime and latamoxef into prostatic fluid in the patients with acute bacterial prostatitis.

Twenty-two patients with acute bacterial prostatitis were treated with cefmenoxime (CMX) or latamoxef (LMOX), which have susceptibilities against various gram-negative bacteria. First 11 patients received a 5- to 12-day course of cefmenoxime and the next 11 received a 6- to 13-day course of latamoxef. All patients were treated successfully except 1 patient with a drug allergy. Diffusion of CMX or LMOX into prostatic fluid in these patients and healthy controls were evaluated. The mean value of CMX in the expressed prostatic fluid was 12.8 micrograms/ml in the patients receiving 2 g of CMX intravenously and 0.7 micrograms/ml in the controls. The mean value of LMOX was 14.0 micrograms/ml in the patients receiving 2 g of LMOX intravenously and 1.2 micrograms/ml in the controls. The diffusion of CMX and LMOX into prostatic fluid in the patients with acute bacterial prostatitis was strikingly higher than that of controls.

Cerebrospinal fluid penetration of cefmenoxime in children with bacterial meningitis.

Blood and cerebrospinal fluid (CSF) concentrations of cefmenoxime were determined either microbiologically or by means of HPLC in 20 children with proven or suspected bacterial meningitis. Sixteen children suffered from bacterial meningitis: causative organisms were Haemophilus influenzae type b (n = 10), Streptococcus pneumoniae (n = 4) and Neisseria meningitidis (n = 2). In these patients the cefmenoxime concentration in the CSF ranged from 0.9 to 12.2 mg/l, with a mean concentration of 4.63 mg/l 1.5-3 h after the last intravenous cefmenoxime application and 24-48 h after initiating therapy with 200 mg cefmenoxime/kg/d in four doses. In eight cases the bactericidal titers of the CSF were examined during therapy. Titers between 1:64 and 1:2,048, exceeding the minimal bactericidal concentration, were found. After five doses of cefmenoxime 50 mg/kg, two CSF cultures showed bacterial growth: one H. influenzae (bactericidal titer in CSF 1:256) and one S. pneumoniae.

Application of mathematical model to multiple-dose experimental chemotherapy for fatal murine pneumonia.

Two beta-lactam antibiotics, cefazolin and cefmenoxime, were administered for 7 days to mice with pneumonia caused by Klebsiella pneumoniae by using dosage regimens that would simulate multiple dosing in usual clinical treatments at dosing intervals of 8 or 12 h. Viable numbers of the bacteria in the lungs were measured at 12- or 24-h intervals. The mathematical model established in a previous single-dose study was applied in this study to explain the time courses of the changes in bacterial count over 7 days. However, because the error in viable count measurements was larger than that in the previous study, the time course of the changes in mean viable count was not regular and the viable count reduction rate changed during multiple dosing, and therefore it was difficult to explain the time course by repeated application of the mathematical model described previously. This study suggests that the changes in pharmacokinetic and pharmacodynamic parameters during multiple dosing need to be considered.

[Clinical study on cefteram pivoxil in asymptomatic bacteriospermia].

In order to understand the clinical efficacy of cefteram pivoxil (CFTM) in the treatment of asymptomatic bacteriospermia, the following studies were performed. 1. Concentrations of CFTM in the semen after oral administration of 200 mg to normal healthy adults (n = 5) reached a maximum level of 0.66 +/- 0.04 microgram/ml in 5 hours after the administration, then decreased rapidly, and averaged 0.15 +/- 0.03 micrograms at 7 hours after administration. 2. Activities of CFTM, cefaclor (CCL) and lomefloxacin (LFLX) against bacteria which were detected in semen (n = 65) (11 aerobic bacterial strains and 48 anaerobic bacterial strains) were retrospectively studied. The study of activities of these 3 agents against anaerobic bacteria showed that CFTM tended to be more active than CCL, LFLX, and similar tendency was noted in LFLX more than CCL against Peptostreptococcus sp. When penetration of antibiotic agents into semen is considered, however, some anaerobic bacteria as well as some aerobic bacteria may not be eradicated or inhibited, hence farther studies are needed to facilitate the selection of proper methods of administration as well as that of effective antibiotics.

[Clinical evaluation of cefteram pivoxil in respiratory tract infections].

The usefulness of cefteram pivoxil (CFTM-PI) was evaluated in 99 cases with respiratory tract infections: 32 cases with acute bronchitis, 51 cases with infectious exacerbations of chronic respiratory diseases and 16 cases with pneumonia. 1. The clinical efficacies included marked improvement in 27 cases, improvement in 51 cases, moderate improvement in 9 cases, no change in 10 cases and deterioration in 2 cases. The improvement rate was 78.8%. 2. Overall effects were excellent in 12 cases, good in 9 cases and fair in 5 cases. There was no case in which efficacy was not observed and the efficacy rate was 80.8%. 3. Bacteriological effects were classified according to the causative organisms. Eradication rate was 80.8% (21 of 26 strains), indicating an excellent antibacterial action of CFTM-PI. In particular, MICs of cefteram were below 0.05 microgram/ml against all 10 strains of Haemophilus influenzae regardless of beta-lactamase production even with an inoculum of 10(8) or 10(6) cells/ml. 4. Side effects rarely occurred and included a slight gastrointestinal irritation in 4 of 99 cases (4%). Two cases which had abnormal elevations of GOT and GPT had abnormal values prior to administration of CFTM-PI. The elevations were slight and it was possible to continue administration. The GOT and GPT values were improved after the end of administration. The above results indicate the usefulness of CFTM-PI in acute respiratory infections and infectious exacerbation of chronic respiratory diseases.