Bacteriological Improvement Research Articles

Impact of the First Twenty-Four-Hour Area Under the Concentration-Time Curve/Minimum Inhibitory Concentration of Vancomycin on Treatment Outcomes in Patients With Methicillin-Resistant Staphylococcus aureus Bacteremia.

Vancomycin regimens are designed to achieve an area under the concentration-time curve/minimum inhibitory concentration (AUC/MIC) ratio ranging between 400 and 600 µg·h/mL in the steady state. However, in cases of critical infections such as bacteremia requiring an early treatment approach, the clinical course may be affected by the AUC/MIC before reaching the steady state, that is, the AUC/MIC values 24 h after the first dose (first 24-h AUC/MIC). This study evaluated the relationship between the first 24-h AUC/MIC and the clinical course of methicillin-resistant Staphylococcus aureus (MRSA) infection. We retrospectively reviewed the records of patients with MRSA bacteremia in a university hospital between 2015 and 2022. The first 24-h AUC/MIC cutoff was set at 300 µg·h/mL based on the results of early response, and eligible patients were divided into groups with a first 24-h AUC/MIC either < 300 µg·h/mL (< 300 group, n = 32) or ≥ 300 µg·h/mL (≥ 300 group, n = 38). The primary endpoint was the rate of treatment efficacy, and the secondary endpoints were time to clinical and bacteriological improvement and 30-day survival rate. Treatment efficacy and 30-day survival rates were not significantly different between the two groups (78.1% vs. 79.0%, P = 0.933 and 83.9% vs. 87.2%, P = 0.674, respectively). Among patients who showed treatment efficacy, the median time to clinical and bacteriological improvement was 11.5 days and 8.0 days in the < 300 and ≥ 300 groups, respectively; compared to the ≥ 300 group, the < 300 group had a significantly longer time to improvement (P = 0.001). The first 24-h AUC/MIC had no effect on the treatment efficacy and 30-day survival rates. However, the time to clinical and bacteriological improvement was significantly prolonged in the < 300 group, indicating that the first 24-h AUC/MIC does not affect the rate of therapeutic efficacy but may affect the treatment period.

Approaches to developing judicious uses of veterinary antibacterial drugs

Development of new veterinary antibacterials is an important and challenging endeavor. Global recognition of antimicrobial resistance as a threat across human, animal, plant, food, and environmental sectors has increased the level of scrutiny on veterinary antibacterial use. Rigorous scientific evaluation of these products has and continues to be the underpinning of effectiveness evaluations and how hazards are identified, characterized, and ultimately used to make evidence-based and risk-based safety decisions. Some scientific factors commonly considered in the development of veterinary antibacterials include the pathogenesis and sequelae of the indicated disease, clinical and bacteriological improvement, dosage regimen (dose amount, route, duration, frequency), and antimicrobial-resistance qualitative risk assessments. Key discussion areas covered are how culture and susceptibility testing help determine if antibacterial effects are primarily responsible for clinical improvement and how pharmacokinetic and pharmacodynamic data can help predict success, aid in defining an adequate dosage regimen, and help minimize resistance emergence and spread.

The Usefulness of Serum CXCR3 Ligands for Evaluating the Early Treatment Response in Tuberculosis: A Longitudinal Cohort Study.

Cell-mediated immunity plays an important role in the pathobiology of tuberculosis (TB). The ligands for CXC chemokine receptor 3 (CXCR3) activate the T-helper type 1 lymphocyte pathway. The CXCR3 ligands are reportedly useful clinical markers for the diagnosis and follow-up of TB. The objective of this study was to assess the utility of CXCR3 ligands for evaluating early treatment responses in TB.We recruited 88 patients who underwent antituberculous chemotherapy. The serum levels of interferon (IFN)-γ and the CXCR3 ligands CXCL9 (monokine induced by IFN-γ [MIG]), CXCL10 (IFN-γ-inducible 10-kDa protein [IP-10]), and CXCL11 (IFN-inducible T-cell α chemoattractant [I-TAC]) were measured before and 2 months after the start of treatment. Treatment responses were divided into “fast” and “slow” based on the clinical, radiological, and bacteriological improvement at 2 months. A change in level of 20% or more at 2 months was defined as “significant.”In patients with treatment success, 58 patients exhibited a fast response and 20 patients exhibited a slow response. Treatment failure occurred in 5 patients, and the diagnoses were changed to non-TB diseases in 5 patients. The levels of all CXCR3 ligands significantly decreased in the fast-response group (P < 0.01) but did not decrease in the other groups. IFN-γ levels showed no significant changes. The ability of significant decreases in marker levels to predict a fast response was evaluated. CXCL9 showed a sensitivity of 83%, and CXCL10 showed a specificity of 100%. Use of various combinations of CXCR3 ligands resulted in improvements in sensitivity (88%–93%), while specificity (92%–96%) was similar to that using single CXCR3 ligands. The decreases in CXCR3 ligand levels were less marked in the 2-month Mycobacterium tuberculosis culture-positive group than in the culture-negative group. There were significant differences in treatment outcomes in terms of 2-month culture positivity (P < 0.001), the significance of CXCL9 decreases (P < 0.01), and the significance of CXCL11 decreases (P < 0.05).In conclusion, CXCR3 ligands may be useful surrogate markers for the evaluation of early treatment response and showed utility as indicators of possible treatment failure in TB.

Role of Glucocorticoids in Ototopical Antibiotic–Steroid Preparations in the Treatment of Chronic Suppurative Otitis Media

It is conventional to use antibiotic-steroid combination eardrops, although the advantage of steroid combination has not been substantiated. The present prospective randomized comparative study is designed to assess the role of glucocorticoids in ototopical antibiotic-steroid preparations in the treatment of chronic suppurative otitis media (CSOM). Pre-treatment clinical assessment, bacteriology of the middle ear discharge and pure tone audiogram were done. CSOM with organisms sensitive to gentamicin were treated either with plain gentamycin (GM) or gentamycin steroid combination (GM-S) eardrops for a period of 3 weeks. Post-treatment clinical, bacteriological and audiogram response was recorded 1 week after discontinuing the eardrops. The post-treatment clinical improvement, bacteriologic improvement and changes in hearing threshold at speech frequencies were analyzed by using unpaired Student's t test and chi(2) tests. The most common organism associated with CSOM was Pseudomonas aeruginosa (33.92%). Clinical improvement was seen in 87.7 and 86.5% cases but bacteriological improvement in only 82.5 and 75% of cases treated with GM and GM-S (p >0.05), respectively. On comparing the pre- and post-treatment pure tone audiograms in 95 patients, 28.9% treated with GM and 30% with GM-S showed deterioration in bone conduction threshold above 5 dB (p >0.05) at speech frequencies. The mean increase in bone conduction in the two groups was 7.7 and 8.57 dB (p >0.05), respectively. Our results indicate that there is no difference in the clinical and bacteriological improvement or ototoxicity either with topical GM or GM-S. Hence, we conclude that it is unnecessary to combine steroids with topical antibiotic preparations for the management of CSOM.

Topical ciprofloxacin versus topical gentamicin for chronic otitis media

We compared the therapeutic efficiency of ciprofloxacin hydrochloride and gentamicin sulfate in the treatment of chronic otitis media. A total of 88 patients aged 9-62 years with chronic suppurative media were randomly placed into two groups. In the first group, 48 patients (54.5%) received topical ciprofloxacin hydrochloride, while in the second group 40 patients (45.5%) received local gentamicin sulfate. Of the 48 patients who received ciprofloxacin hydrochloride, 42 (87.5%) were cured, while in 6 patients (12.5%) the treatment failed. In the gentamicin group, 12 (30%) of the patients were cured, while 28 patients showed no clinical or bacteriological improvement. Topical ciprofloxacin is safe and more efficacious and efficient than topical gentamicin in the treatment of acute exacerbation of chronic suppurative otitis media.

LOW LEVEL LASER THERAPY (LLLT) WITH NITROGEN AND HELIUM NEON LASERS IN MULTIPLE DRUG RESISTANT PULMONARY TUBERCULOSIS:

The present study reports on 25 patients with multiple drug resistant chronic pulmonary tuberculosis (MDR-PTB), comprising of 13 males and 12 females. Intravenous (IV) helium neon (HeNe) and/or nitrogen (N2) laser therapy was administered together with intracavitary (IC) N2 laser therapy. Ten sittings of IV laser therapy were given on alternate days or weekly according to the protocol and N2 laser IC irradiation was administered weekly for a period of 3 months, and monthly thereafter for another three months. Patients were followed up for 3 to 6 months post-therapy. All the patients included in the study were hospitalized during the therapy and continued to receive chemotherapy concomitantly with the LLLT. Of the 25 patients included in this study, five were lost to follow up. Clinical and bacteriological improvement was seen in 14 (70%) and 15 (75%) of the patients, respectively, while haematological and radiological improvement was observed in 14 (70%) and 17 (85%) of the patients, respectively. No major side effects were noted. Two patients developed pneumothorax and three had haemoptysis after the procedure, which did not pose a problem. There was no mortality. It can therefore be concluded from this preliminary clinical trial that intravenous and intracavitary laser therapy acts as a useful adjuvant to chemotherapy in the treatment of MDR-PTB, and that there is a strong possibility that LLLT on its own may well be very usefu1 in the therapy of new, untreated cases of PTB.

Timentin in the treatment of symptomatic complicated urinary tract infections in adult patients

The safety and effectiveness of Timentin were evaluated in 34 adult patients with symptomatic complicated urinary tract Infections, principally due to multiply-drug-resistant bacteria. Although a wide variety of organisms, particularly gram-negative bacilli, were found, Escherichia coli was the most frequent, accounting for 14 of 45 (31 percent) pathogens isolated. Ten (22 percent) isolates were Pseudomonas aeruginosa; 11 (24 percent) were Proteus or Morganella species; three (7 percent) were Citrobacter; one (2 percent) was Klebsiella pneumoniae; two (4 percent) were Staphylococcus aureus; and two (4 percent) were enterococci. Ninety-three percent of all pathogens isolated produced a beta-lactamase. Eight (24 percent) infections were polymicroblal; seven (21 percent) were associated with bacteremia. Clinical improvement occurred in 30 of 34 (86 percent) patients. All bacteremias were cured. Although bacteriologic cure occurred in only 32 percent of patients, control of sepsis and temporary eradication of bacteria (bacteriologic Improvement) occurred in 96 percent. Not surprisingly, the rates of relapses and reinfections were high. It was concluded that Timentin is a useful agent in the management of complicated urinary tract infection and offers clinicians an alternative to more toxic antibiotics, such as aminoglycosides.

A simple oral antimicrobial regimen effective in severe chronic bronchial suppuration associated with culturable Haemophilus influenzae.

Three grams of amoxycillin administered twice daily for seven days, as an oral powder (Amoxil 3G sachets, Bencard) dispersed in water, to 17 patients with bronchiectasis resulted in striking clinical, spirometric and bacteriological improvement in 11 of 12 patients who were producing purulent sputum from which Haemophilus influenzae was cultured by a selective bacteriological technique (Roberts & Cole, 1980). In the five patients from whose sputum this organism could not be cultured, and in one from whom it could, there was no improvement. Untoward effects were limited to nausea in one patient and acceptability of the regimen by the remaining patients was unanimous. There was no evidence of accumulation of the drug in serum or sputum. The rapidity of effect and oral form of the treatment suggest that it may provide a simple out-patient regimen for chronic bronchial sepsis and severe purulent exacerbations of chronic bronchitis from which H. influenzae can be cultured.

Evaluation of ceftazidime in the treatment of severe infection

Ten seriously ill patients with infections caused by multiply-resistant organisms were treated with intravenous ceftazidime. Nine showed clinical and bacteriological improvement. Apart from one patient who developed a mild transienterythematous rash, no side effects or toxicity was found.

Electrophysiological evidence for motor unit impairment during the treatment of leprosy

Although neuropathy is the most striking feature in leprosy, the effects of various drugs are usually assessed by dermatological and bacteriological improvement. This short term electrophysiological study shows that both antileprosy drugs, DDS and Sulforthomidine, do not affect the insidious deterioration of motor unit condition in lepromatous and borderline BT patients. Differences observed in the results of the two groups were discussed.

Clinical Evaluation of Tobramycin in Respiratory and Systemic Infections in Immunodepressed and Normal Patients

Twelve patients with acute or chronic pneumonia due mainly to gram-negative bacilli, two patients with pseudomonas endocarditis, and two patients with seratia sepsis were treated with 80-160 mg of tobramycin in two daily doses. Fourteen infected patients with underlying leukemia or lymphoma received this dose of tobramycin combined with cefazolin or penicillin. Most respiratory infections were cured or markedly improved. with eradication or significant reduction in the number of infecting organisms. One case of pseudomonas endocarditis and both cases of serratia sepsis were also cured. Combined treatment with tobramycin and beta-lactam antibiotics resulted in clinical and bacteriological improvement in 50% of systemic immunodepressed patients with sepsis and/or pneumonia.

Laboratory and clinical studies on carfecillin.

This paper describes our findings in the uses of carfecillin for treatment of 22 patients with urinary tract infections in a hospital urological department. Peak serum levels of 5 g/ml were reached 1 h after oral administration of 1000 mg. Clinical and/or bacteriological improvement was found in 90 % of patients. One side effect, an allergic rash, was noted. During the treatment changes in the gut flora of the patients occurred leading to an increase in the number of carbenicillin resistant bacteria and increased rate of colonization with large numbers of Candida spp.

Cephacetrile: clinical evaluation in 27 patients.

Cephacetrile, a new derivative of 7-aminocephalosporanic acid, was evaluated in 27 patients. Soft tissue infections due primarily to gram-positive cocci were treated in 16 patients; 12 had bacteriological and clinical cure, and 4 improved but the lesions resolved incompletely or cultures remained positive. Seven of eight patients with respiratory tract infections were cured, including three with pneumococcal pneumonia; the eighth proved to have a noninfectious process and failed to respond. Two patients with acute urinary tract infections due to Escherichia coli had prompt clinical and bacteriological improvement, but follow-up was incomplete. One patient with sepsis due to Staphylococcus aureus expired. Laboratory abnormalities observed during cephacetrile therapy included mild eosinophilia in four patients, thrombocytosis in nine, direct Coombs' test positivity in four, and an elevated serum glutamic pyruvic transaminase in eight patients. No evidence of nephrotoxicity was detected. Severe superinfection due to Enterobacter species was observed in one patient. Mean peak serum concentrations of cephacetrile were 22, 69, and 104 mug/ml after 1 g intramuscularly, 1 g intravenously, and 1.5 g intravenously, respectively. Thus, in early studies cephacetrile was efficacious for selected bacterial infections, but determination of its comparative value within the cephalosporin group of antibiotics requires further clinical investigation.

A case of disseminated nocardiosis

The clinical, histopathological, and bacteriological data are reported in the case of a patient with nocardiosis of acute pleuropulmonary onset. Early treatment with penicillin and sulphisoxazole was followed by transient clinical and bacteriological improvement but did not prevent cerebral abscess formation and diffuse septic metastasis leading to death from respiratory insufficiency. After bacteriological identification of the Nocardia strain, a study was made of its in vitro susceptibility to antibiotics and to the patient's serum after intravenous administration of penicillin and sulphisoxazole.

Study of Serum Glycoproteins in Pulmonary Tuberculosis

SUMMARY AND CONCLUSION The average serum glycoprotein levels in 45 untreated (new) cases and 35 treated chronic cases of proved pulmonary tuberculosis without any complications and of 24 normal healthy adults (medical students) were estimated. The method of estimation adopted was a slight modification of that of Lustig and Langer 2 as employed by Weimer and Moshin. 3 It is concluded from this study that the serum glycoprotein level rises in cases of pulmonary tuberculosis. This rise is directly proportional to the severity of the disease and to the positivity of sputum. It corresponds to erythrocyte sedimentation rate values estimated by the Wintrobe 7 method. The serum glycoprotein levels are thus a good indication of the severity and activity of disease. The return of serum glycoprotein levels to normal was commensurate with clinical, radiologic and bacteriologic improvement after at least six months of adequate, regular, uninterrupted chemotherapy with standard drugs. No significant difference was noticed between the two groups of fresh patients viz., those who had treatment in hospital and those treated in their homes.

癩患者剖検例の肝臓の病理学的研究(第2報)

The following results were obtained from the macro- and microscopical examinations on the liver of autopsy material of 20 leprous cases (lepromatous 19 and neural 1).1) The degree of histological and bacteriological improvement of lepromata in the liver is proportionate to that of lepromata in the skin.In the relapse after temporary improvement, the course of lepromata in the liver is in proportion to that of skin lesion, but the liver change is not always subordinate to the skin lesions. Sometimes, the local relapse of lesion takes place in the liver, which can be the sourse of aggravation of skin and general disease.2) In some cases the progresses of development of change in the lobule differ from that in the interstitium.3) There exist macroscopically yellowish and whitish lepromata. This difference of the color tone is originating in the quantity of lipid in lepra cells of the lepromata.4) The distribution of hematogenously disseminated leprosy bacilli is not always equable, but various in each loubule or in part of the lobule itself.5) Though many factors except leprosy can influence upon the liver cells, atrophy, necrosis and disappearance of liver cells may be attributed directly or indirectly to leprosy, for example the pressure of numerous lepromata in the lobule, or the local congestion due to stenosis or obliteration of the central veins caused by the leprous changes.6) The fatty degeneration caused by leprosy takes the type of peripheral fatty degeneration.7) Leprosy shows a stronger tendency than tuberculosis to affect the central veins.8) The proliferation of the interstitium is generally in proportion to the degree of changes in liver, and is also influenced by the ratio occupied by the improving lepromata. And there seems to exisit the disparity in the intensity of connective tissue reaction between tie individuals.9) The elastic fiber is weaker in resistense than the reticular and collagenic fibers, and easily broken and disappear and difficult to regenerate. Besides such remarkable breaking and disppearence, new growth of the elastic fibers, though in a slight degree, can be observed in some cases.10) The vessels, regarding the tunica intima of the arteries, in the interstitium undergo leprous changes often, and sometimes the veins are invaded.11) The individual differences of the intensity of connective tissue reaction participate in the thickning of the liver capsule as well as the proliferation of interstitium.

Isoniazid in Pulmonary Tuberculosis

Sixty two cases of active pulmonary tuberculosis treated with isonicotinic acid hydrazide over a period of from 90 to 297 days have been reported. The drug was administered in dosages of 4 mgm. and 8 mgm. per kilo of body weight. Twenty six received combined treatment of dihydrostreptomycin and isoniazid. In spite of the small number of cases it is considered that some of the results are significant. General manifestations of pulmonary tuberculosis disappeared in two to three weeks, temperature becoming normal, with considerable weight gain and development of voracious appetite. Cough and expectoration were completely eliminated. Of 32 positive cases that received isoniazid, 16 reverted to negative. Of 21 positive cases that received combined dihydrostreptomycin and isoniazid 10 reverted. The reversions were higher in the early exudative and mixed cases. All laryngeal and endobronchial lesions responded favorably. Roentgenological changes were not as impressive as the clinical benefits, but 36 out of 55 patients showed some improvement, mostly in the early exudative and mixed cases. The action of isoniazid seems to be mostly limited to the exudative element of the tuberculous process. No demonstrable clinical, radiological, or bacteriological improvement was found when the dosage of isoniazid was increased from 4 to 8 mgm. per kilo of body weight. However, an accentuation in toxic manifestations was evident. From a therapeutic standpoint, 4 mgm. of isoniazid per kilo of body weight provides an adequate concentration and satisfactory dosage. Combined treatment with dihydrostreptomycin and isoniazid requires further studies before the advantages and limitations of such therapy can be properly evaluated. It has been confirmed that an initial, natural or spontaneous as well as an acquired resistance to isoniazid exists and has to be considered in the treatment of patients. Toxic symptoms are practically non-existant on a 4 mgm. per kilo of body weight dosage. These respond quickly to treatment and disappear when the drug is discontinued. Although no increase in the total proteins of the blood was found, an elevation of the globulin fraction and inversion of the albumen-globulin ratio was observed in 14 patients, for which we have no satisfactory explanation. Isonicotinic acid hydrazide is an effective drug in the treatment of pulmonary tuberculosis. Further studies toward solving the many therapeutic problems arising from its use should be continued.

Isoniazid in lepromatous leprosy

1. (1) Isoniazid was given a 6-months trial in eight patients suffering from lepromatous leprosy, some of whom had responded very poorly to previous sulphone treatment. 2. (2) Some form of lepra reaction occurred in all cases, causing treatment to be temporarily interrupted in two instances and dosage to be limited in two others. 3. (3)There was no definite clinical evidence of improvement or deterioration during the trial. 4. (4) There was some evidence, not statistically significant, of bacteriological improvement followed by relapse in half the cases.In the other half there was no change. 5. (5) Sedimentation rates fell in all cases.There were no unequivocal alterations in the results of other laboratory investigations during the course of the trial.The histological reaction is described. 6. (6) It was concluded that isoniazid, used alone under the conditions of this trial, was not an effective treatment for lepromatous leprosy.

Treatment with aureomycin of localized pasteurella multocida infection

Summary A chronic, localized infection of thenose due to Past. multocida and originating in all likelihood from a horse was treated with aureomycin given locally and perorally. The clinical response was favorable and the organism disappeared. However, it could be demonstrated again during the subsequent attack of cellulitis caused by hemolytic streptococcus and Staph. aureus , which was treated successfully with penicillin. The necrotic tissue was removed. The clinical and bacteriological improvement following cessation of all therapy has continued. In vitro, this strain proved to be highly susceptible to aureomycin and did not develop resistance to this antibiotic.

Friedländer's bacillus meningitis treated with streptomycin

A fatal case of type b Friedländer's bacillus meningitis, septicemia, cholecystitis and liver abscess in a sixty year old female is reported. Although intramuscular and and intrathecal therapy with streptomycin resulted in striking bacteriologic improvement, the patient suddenly died on the sixth day of the disease from an undetermined cause. This brings the total reported cases of Friedländer-Aerogenes meningitis to fifty-four. Before the advent of chemotherapy only one recovery was reported; since then, four additional recoveries have been reported in which the sulfonamides or streptomycin have been used. Intramuscular and intrathecal administration of streptomycin is probably the treatment of choice although only one of several patients treated in this fashion has survived.