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Query: UMLS:C0032285 (pneumonia)
 54,520 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pefloxacin and ciprofloxacin are two new quinoline carboxylic acid derivatives that have activity in vitro against a wide range of gram-negative bacteria, including Pseudomonas aeruginosa. Using a well-standardized model of Pseudomonas pneumonia in neutropenic guinea pigs, we tested the efficacy in vivo of these new agents. Both were highly effective in increasing survival and decreasing bacterial counts in the lungs of surviving animals. Pefloxacin and ciprofloxacin were significantly better (P less than 0.05) than aminoglycosides or beta-lactams tested in prior studies with this model, and they were as effective as combination therapy with aminoglycosides and beta-lactams. Resistance to either ciprofloxacin or pefloxacin did not emerge during the study period. Further studies with these drugs in the therapy of Pseudomonas sp. infections are warranted.
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PMID:Activities of pefloxacin and ciprofloxacin in experimentally induced Pseudomonas pneumonia in neutropenic guinea pigs. 315 36

The efficacy of selective decontamination of the oral cavity and GI-tract in the treatment of established gram-negative pneumonia in critically ill patients was evaluated in a prospective open trial. 25 patients with pneumonia caused by Enterobacteriaceae or Pseudomonadaceae were studied. All patients were mechanically ventilated (range 2-60 days). Non-absorbable antibiotics (polymyxin E 100 mg, tobramycin 80 mg, amphotericin B 500 mg) were administered through the nasogastric tube four times a day. The oral cavity was decontaminated with an ointment containing 2% of the same antibiotics, applied to the buccal mucosa four times a day. For systemic therapy a combination of tobramycin (3-6 mg X kg-1) with either cefotaxim (50-100 mg X kg-1) or ceftazidime (100 mg X kg-1) was given both intravenously and by aerosol (50% IV dose/5 ml saline) four times a day. Eradication of pathogens from the respiratory tract was achieved in 24 patients within 9 days (median 5 days). The cure rate was 96%. Two patients had a relapse. Neither recolonization with resistant organisms nor supra-infections were found for the remaining period of mechanical ventilation (up to 60 days), also after systemic/aerosol therapy had been discontinued. Only 3 patients died (12%).
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PMID:Nosocomial gram-negative pneumonia in critically ill patients. A 3-year experience with a novel therapeutic regimen. 354 63

The therapeutic efficacy of ciprofloxacin, an investigational quinoline derivative, was compared with those of ticarcillin and tobramycin in guinea pigs with experimental Pseudomonas aeruginosa pneumonia. Guinea pigs challenged with tracheal instillations of 10(8) CFU of P. aeruginosa developed acute pneumonia, for which survival rates were: controls, 0%; ticarcillin treatment, 37%; ciprofloxacin treatment, 57%; and tobramycin treatment, 69%. Intrapulmonary killing of P. aeruginosa was greater (P less than 0.05) in animals treated with ciprofloxacin or tobramycin than in groups treated with ticarcillin. A more chronic, nonfatal form of bronchopneumonia caused by P. aeruginosa was induced with agar beads impregnated with bacteria for pulmonary challenge. In this model, ciprofloxacin treatment resulted in significantly (P less than 0.001) greater intrapulmonary killing than did any other therapy. These data suggest that ciprofloxacin may be useful in the treatment of acute and more-chronic forms of pulmonary infection caused by P. aeruginosa.
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PMID:Comparative activities of ciprofloxacin, ticarcillin, and tobramycin against experimental Pseudomonas aeruginosa pneumonia. 643 86

The activities of 25 8-aminoquinolines were compared in tests assessing the ability of the compounds to inhibit the growth of Pneumocystis carinii in culture. Six compounds were effective at or below 0.03 microM: CDRI 80/53, NSC19894, NSC305805, NSC305812, WR182234, and primaquine. Four others were effective at between 0.2 and 0.03 microM: NSC305835, WR225448, WR238605, and WR242511. Fourteen drugs were also tested in a standard model of P. carinii pneumonia in rats at daily doses of 2 mg/kg of body weight in drinking water. CDRI 80/53, NSC305805, NSC305835, and WR225448 were extremely effective in the animal model. The effectiveness of WR238605, WR242511, and primaquine in the rat model has been reported elsewhere (M. S. Bartlett, S. F. Queener, R. R. Tidwell, W. K. Milhouse, J. D. Berman, W. Y. Ellis, and J. W. Smith, Antimicrob. Agents Chemother. 35:277-282, 1991). The length of the alkyl chain separating the nitrogens in the substituent at position 8 of the quinoline ring was a strong determinant of anti-P. carinii activity.
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PMID:8-aminoquinolines effective against Pneumocystis carinii in vitro and in vivo. 825 40

The objective of this prospective, randomized, double-blind study was to evaluate the effect of the addition of mupirocin to the 'classical' topical SDD regimen (tobramycin 80 mg, polymyxin E 100 mg, amphotericin B 500 mg) on the development of ICU-acquired infections due to gram-positive bacteria. The study was carried out in an intensive care unit (ICU) of a 1400-bed community hospital. All patients admitted to the ICU during a 16-month period, who were expected to require mechanical ventilation for more than 24 hours, were randomized to receive either the 'classical' SDD regimen (Group A) or a modified regimen with mupirocin (Group B). Data from 223 patients requiring mechanical ventilation for at least 48 hours, who were neither infected nor receiving antibiotics on ICU admission, was analysed. A 2% paste containing tobramycin, polymyxin E and amphotericin B was applied every 6 hours in the oropharynx to the patients in Group A, while in Group B this formula was modified with the addition of 2% mupirocin. In Group B 0.2 ml of a 2% mupirocin ointment was also applied four times daily in both nostrils. Patients in Group A received a soft paraffin ointment as a placebo indistinguishable from mupirocin. Patients in both groups received the classic SDD regimen through the nasogastric tube. Systemic antibiotic prophylaxis was not used. Data on lower airway infection, and blood infection, infections of intravascular catheters, antibiotic consumption and expenditures for antibiotics were analysed. The diagnosis of ventilator-associated pneumonia (VAP) was based on quantitative cultures of protected specimen brush samples (PSB) or on the results of distal broncho-alveolar lavage (BAL). One hundred and four patients received the 'classical' SDD and 119 the modified regimen. Overall 29 patients, 20 in Group A and nine in Group B (p < 0.02) had a total of 33 cases of pneumonia. There were 23 episodes of pneumonia in Group A and 10 in Group B (p < 0.02). Gram-positive bacteria were isolated from samples in 17 episodes in Group A and six in Group B (p < 0.02). Staphylococcus aureus was isolated in nine cases of pneumonia in Group A and once in the 'mupirocin' group (p < 0.05). MRSA were isolated in seven out of nine cases in Group A and in the only case in Group B. There were no differences in the isolation of gram-negative bacilli. Antibiotic consumption and cost were lower in Group B. In conclusion, our data show that the topical use of a modified formula of SDD, with the addition of mupirocin to the oral paste and in the anterior nares, is associated with a reduction in lung infections caused by gram-positives and in a reduction in antibiotic consumption and in the overall expenditure for antibiotics.
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PMID:Reduction in gram-positive pneumonia and antibiotic consumption following the use of a SDD protocol including nasal and oral mupirocin. 1158 66

In the current study we investigated the antibacterial activity of fragrance ingredients against Legionella pneumophila, a causative agent of severe pneumonia. Among the 41 different fragrance ingredients tested, we found that the natural fragrance ingredients oakmoss (OM) and birch tar oil (BT), which contain many components, exhibit potent antibacterial activity. The minimum inhibitory concentration (MIC, % (v/v)) of OM and BT were 0.0020 and 0.0024, respectively and were lower than that of cinnamic aldehyde (0.0078), which has been previously shown to possess high antimicrobial activity. In a time-kill assay of OM and BT at MIC and two times MIC, the colony forming units (CFU) of the microbe were reduced to between 10(-3) to 10(-4) of the original CFU after 1 h co-incubation. After this time, the CFU gradually decreased in number, but remained above detection levels even after a 48-h co-incubation, except for BT at two times MIC. In contrast, at a concentration of 0.1% OM and BT (approximately 50 times MIC), CFU were not detected after co-incubation for 1 h. Another 18 fragrance ingredients including ketone, aldehyde, lactone, acid, phenol derivative, aliphatic alcohol and quinoline also exhibited a lesser degree of antibacterial activity against L. pneumophila at a MIC of less than 0.10.
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PMID:The antibacterial activity of fragrance ingredients against Legionella pneumophila. 1948 26

The incidence of ventilator-associated pneumonia (VAP) is particularly high in patients with trauma. The efficacy and safety of selective digestive decontamination (SDD) was not studied extensively. We aimed in our randomized double-blind, placebo-controlled study to evaluate whether SDD prevents VAP onset in multiple trauma patients. All adult patients admitted in our intensive care unit for multiple trauma with a predicted duration of mechanical ventilation (MV) over 48 hours were included. We included 44 patients who were divided into 4 groups: group A receiving subglottic and gastric treatment suspension (polymyxin E 100 mg, vancomycin 1 g, and amphotericin B 500 mg), group B receiving placebo, group C receiving subglottic placebo and gastric treatment suspension, and group D receiving subglottic treatment suspension and gastric placebo. The suspension was given 4 times a day during 7 consecutive days. To this topical treatment, we associated an intravenous administration of cefotaxime (1 g 3 times a day during 4 consecutive days). The incidence of VAP in the 4 groups was, respectively, 45.5%, 46.2%, 22.2%, and 27.3% (P=0.236). In multivariate analysis, none of the 3 tested regimens was identified as a protective factor against VAP. However, prolonged duration of MV was the only independent factor predicting VAP onset (odds ratio=1.1; 95% confidence interval [1.1-1.4]; P=0.049).
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PMID:Does selective digestive decontamination prevent ventilator-associated pneumonia in trauma patients? 2356 85

Macrolides, polyketide natural products, and their 15-membered semi-synthetic derivatives are composed of substituted macrocyclic lactone ring and used primarily as potent antibiotics. Recently their usefulness was extended to antimalarial and anti-inflammatory area. Hybrid macrolides presented in this article are the next generation semi-synthetic compounds that combine pharmacophores from antibacterial, antimalarial and anti-inflammatory area with 14- and 15-membered azalide scaffolds. Antibacterial azalide hybrids with sulphonamides showed improved activity against resistant streptococci while quinolone conjugates demonstrated full coverage of respiratory pathogens including macrolide resistant strains and their efficacy was confirmed in mouse pneumonia model. Antimalarial macrolide hybrids, mainly involving (chloro)quinoline pharmacophores, showed outstanding activity against chloroquine resistant strains, favourable pharmacokinetics, promising in vivo efficacy as well as encouraging developmental potential. Anti-inflammatory hybrids were obtained by combining macrolides with corticosteroid and non-steroidal anti-inflammatory drugs. They were found active in in vivo animal models of locally induced inflammation, asthma, inflammatory bowel disease and rheumatoid arthritis and demonstrated improved safety over parent steroid drugs. Overall, macrolide hybrids possess significant potential to be developed as potent novel medicines in therapeutic areas of utmost pharmaceutical interest.
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PMID:Macrolide Hybrid Compounds: Drug Discovery Opportunities in Anti- Infective and Anti-inflammatory Area. 2769 49

An outbreak of novel coronavirus-related pneumonia COVID-19, that was identified in December 2019, has expanded rapidly, with cases now confirmed in more than 211 countries or areas. This constant transmission of a novel coronavirus and its ability to spread from human to human have prompted scientists to develop new approaches for treatment of COVID-19. A recent study has shown that remdesivir and chloroquine effectively inhibit the replication and infection of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2, 2019-nCov) in vitro. In the United States, one case of COVID-19 was successfully treated with compassionate use of remdesivir in January of 2020. In addition, a clinically proven protease inhibitor, camostat mesylate, has been demonstrated to inhibit Calu-3 infection with SARS-CoV-2 and prevent SARS-2-spike protein (S protein)-mediated entry into primary human lung cells. Here, we systemically discuss the pharmacological therapeutics targeting RNA-dependent RNA polymerase (RdRp), proteinase and S protein for treatment of SARS-CoV-2 infection. This review should shed light on the fundamental rationale behind inhibition of SARS-CoV-2 enzymes RdRp as new therapeutic approaches for management of patients with COVID-19. In addition, we will discuss the viability and challenges in targeting RdRp and proteinase, and application of natural product quinoline and its analog chloroquine for treatment of coronavirus infection. Finally, determining the structural-functional relationships of the S protein of SARS-CoV-2 will provide new insights into inhibition of interactions between S protein and angiotensin-converting enzyme 2 (ACE2) and enable us to develop novel therapeutic approaches for novel coronavirus SARS-CoV-2.
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PMID:Pharmacological Therapeutics Targeting RNA-Dependent RNA Polymerase, Proteinase and Spike Protein: From Mechanistic Studies to Clinical Trials for COVID-19. 3232 2

Lascufloxacin hydrochloride (AM-1977) is a novel 8-methoxy fluoroquinolone antibacterial agent with a unique pharmacophore at the 1st and 7th positions of the quinoline nucleus developed by Kyorin Pharmaceutical Co., Ltd. (Tokyo, Japan). It has been approved by the Japanese Ministry of Health, Labour and Welfare (MHLW) for treatment of respiratory tract and ear, nose and throat infections including community-acquired pneumonia and otorhinolaryngological infections, and shows great promise against fluoroquinolone-resistant strains of major pathogens which infect the respiratory tract. It is suitable for treating infections caused by Staphylococcus, Streptococcus, Pneumococcus, Moraxella (Branhamella) catarrhalis, Klebsiella, Enterobacter, Haemophilus influenzae, Legionella pneumophila, Prevotella and Mycoplasma pneumoniae that are sensitive to this drug.
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PMID:Lascufloxacin hydrochloride to treat bacterial infection. 3252 35


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