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Query: UMLS:C0032285 (pneumonia)
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The new respiratory fluoroquinolones (gatifloxacin, gemifloxacin, levofloxacin, moxifloxacin, and on the horizon, garenoxacin) offer many improved qualities over older agents such as ciprofloxacin. These include retaining excellent activity against Gram-negative bacilli, with improved Gram-positive activity (including Streptococcus pneumoniae and Staphylococcus aureus). In addition, gatifloxacin, moxifloxacin and garenoxacin all demonstrate increased anaerobic activity (including activity against Bacteroides fragilis). The new fluoroquinolones possess greater bioavailability and longer serum half-lives compared with ciprofloxacin. The new fluoroquinolones allow for once-daily administration, which may improve patient adherence. The high bioavailability allows for rapid step down from intravenous administration to oral therapy, minimizing unnecessary hospitalization, which may decrease costs and improve quality of life of patients. Clinical trials involving the treatment of community-acquired respiratory infections (acute exacerbations of chronic bronchitis, acute sinusitis, and community-acquired pneumonia) demonstrate high bacterial eradication rates and clinical cure rates. In the treatment of community-acquired respiratory tract infections, the various new fluoroquinolones appear to be comparable to each other, but may be more effective than macrolide or cephalosporin-based regimens. However, additional data are required before it can be emphatically stated that the new fluoroquinolones as a class are responsible for better outcomes than comparators in community-acquired respiratory infections. Gemifloxacin (except for higher rates of hypersensitivity), levofloxacin, and moxifloxacin have relatively mild adverse effects that are more or less comparable to ciprofloxacin. In our opinion, gatifloxacin should not be used, due to glucose alterations which may be serious. Although all new fluoroquinolones react with metal ion-containing drugs (antacids), other drug interactions are relatively mild compared with ciprofloxacin. The new fluoroquinolones gatifloxacin, gemifloxacin, levofloxacin, and moxifloxacin have much to offer in terms of bacterial eradication, including activity against resistant respiratory pathogens such as penicillin-resistant, macrolide-resistant, and multidrug-resistant S. pneumoniae. However, ciprofloxacin-resistant organisms, including ciprofloxacin-resistant S. pneumoniae, are becoming more prevalent, thus prudent use must be exercised when prescribing these valuable agents.
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PMID:A Review of New Fluoroquinolones : Focus on their Use in Respiratory Tract Infections. 1715 73

Macrolides have enjoyed continued use for over 40 years, being increasingly used for the treatment of respiratory tract infections. Newer macrolides have been introduced that show improved absorption after oral administration, better gastrointestinal tolerance, and delivery of increased amounts of drug to the infection site. Macrolides are commonly used in community-acquired pneumonia, as well as in atypical pneumonia and legionellosis. The newer macrolides, in comparative studies, have been shown to be as affective as the conventional therapies for treating acute otitis media, acute sinusitis and acute pharyngitis, with a low incidence of side-effects. However, dosing can be simplified because of their unique pharmacokinetic properties. Limitations in the use of macrolides for respiratory infections include rather marginal activity in the most severe cases of Haemophilus influenzae infections, lack of activity against Klebsiella and other coliforms, which precludes their use as single agents in the therapy of pneumonia in patients with significant underlying disease or in the elderly, and development of resistance in streptococci and staphylococci.
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PMID:The use of macrolides in respiratory tract infections. 1861 79

Twelve normal monkeys inoculated on the mucous membranes of the nose or nose and mouth with a strain of Bacillus influenzae; originally isolated in pure culture from the pleural exudate of a case of empyema following influenzal pneumonia in man and subsequently raised in virulence by animal passage, developed an acute self-limited respiratory disease of from 3 to 5 days duration, characterized by sudden onset with profound prostration, the development of rhinitis and tracheobronchitis, with sneezing, cough, and the outpouring of a scanty mucoid, or mucopurulent exudate, a variable febrile reaction, and either a leucopenia or no significant change in the leucocyte count. This disease was complicated in five instances by purulent sinusitis of one or both antra, in three by bronchopneumonia. Bacillus influenzae was recovered at autopsy from the lesions of the disease either in pure culture or in association with organisms that are normal inhabitants of the upper respiratory tract of monkeys. Of ten normal monkeys injected intratracheally with the same strain of Bacillus influenzae, seven developed bronchopneumonia, two developed tracheobronchitis without pneumonia, and one resisted infection. The general symptoms and duration of the disease were similar to those of the preceding group. There were a severe cough and accelerated respirations. Bacillus influenzae was recovered in pure culture from the lungs, bronchi, or trachea in the animals killed during the active stage of the disease. It disappeared promptly from the respiratory tract with recovery. The significance of the first series of experiments in which monkeys were inoculated in the upper respiratory tract is twofold. First, they establish the fact that Bacillus influenzae can initiate in monkeys an acute infection of the normal mucous membranes of the upper respiratory tract; that is, it can act as a primary incitant of respiratory infection without the assistance of a preceding or concomitant contributing cause. In this respect it differs radically from the pneumococcus and Streptococcus haemolyticus, since experiments previously reported(2, 4) have shown that neither of these organisms possesses the property of initiating an infection of the normal mucous membranes of the upper respiratory tract of monkeys, even though the strains used were incalculably more virulent for monkeys than the strain of Bacillus influenzae used in the foregoing experiments. Secondly, the experiments show that Bacillus influenzae infection of the mucous membranes of the upper respiratory tract may spread by continuity to the paranasal sinuses, setting up an acute sinusitis, that it spreads readily to the lower respiratory tract, producing a tracheobronchitis and permitting the ready invasion of secondary bacteria, and that it may penetrate as far as the terminal bronchioles, alveolar ducts, atria, and alveoli, there setting up a bronchiolitis and true bronchopneumonia. In these respects it likewise differs radically from the pneumococcus and Streptococcus haemolyticus which do not possess these pathogenic properties as previous experiments have shown.(2, 4) The bearing of these facts on the possible etiologic relation of Bacillus influenzae to influenza is important, since they show that Bacillus influenzae possesses certain definite primary pathogenic properties which distinguish it and therefore separate it from the group of recognized secondary organisms in influenzal complications, of which the pneumococcus and the streptococcus are the most frequent. The possible etiologic relation of Bacillus influenzae to influenza is further supported by the character of the respiratory disease that occurred in the monkeys. The sudden onset with profound prostration, the absence of leucocytosis or often a leucopenia, the congestion of the mucous membranes of the respiratory tract, the development on the 2nd or 3rd day of an irritative cough due to an inflammatory tracheitis or tracheobronchitis, the brief self-limited course of the infection, and the irregular febrile reactions are all characteristic of influenza. Many of these symptoms were in striking contrast with the symptoms and course of pneumococcus or streptococcus infections in monkeys in which there were no prostration at onset, invariable leucocytosis, and infrequent cough developing only late in the disease. While all the above features of the disease produced in monkeys are characteristic of influenza in man, none are pathognomonic and, in fact, it is doubtful whether uncomplicated influenza possesses any pathognomonic features by which it may be diagnosed certainly in the absence of an epidemic. Even during epidemic times many respiratory infections arise which, though presumably influenza, it is impossible to diagnose as such with certainty. Nor does pathology help in this respect, since there would appear to be no established distinctive lesions of uncomplicated influenza in man, nor for that matter of the complications of influenza, apart from the complications which have been ascribed by Pfeiffer,(5) MacCallum,(6) Wolbach,(7) and others to infection with Bacillus influenzae because of the association of Bacillus influenzae in pure culture with these complications. For these reasons, although the disease produced in monkeys appears to be essentially identical with influenza in man with respect to its clinical course and complications, it is impossible to determine certainly whether it is actually so. The experiments are advanced, therefore, as evidence in favor of the etiologic relation of Bacillus influenzae to influenza, though they do not permit of a definite conclusion in this respect. Their bearing upon the relation of Bacillus influenzae to certain of the complications of influenza would appear to be reasonably conclusive. The recovery of Bacillus influenzae in pure culture at autopsy from the antra, from the trachea and bronchi, and from the lungs in some of the animals developing sinusitis, bronchiolitis, and a characteristic type of bronchopneumonia confirms by animal experiment the etiologic relation of Bacillus influenzae to these complications of influenza, which hitherto has rested solely upon the frequent association of the influenza bacillus with these lesions in man. The production of tracheobronchitis and the same type of bronchopneumonia by the intratracheal injection of Bacillus influenzae in the second series of experiments serves as additional confirmation of this, but has no direct bearing on the etiologic relation of Bacillus influenzae to uncomplicated influenzae.
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PMID:STUDIES ON EXPERIMENTAL PNEUMONIA : IX. PRODUCTION IN MONKEYS OF AN ACUTE RESPIRATORY DISEASE RESEMBLING INFLUENZA BY INOCULATION WITH BACILLUS INFLUENZAE. 1986 70

The majority of cold and flulike illnesses are caused by human rhinoviruses (HRVs). Improved detection of HRV has shown that HRVs are also associated with more serious illness, such as exacerbation of asthma, wheezing illnesses in children, chronic obstructive pulmonary disease, cardiopulmonary disease, and fatal pneumonia in immune-compromised patients. HRV is a major cause of acute viral respiratory tract infections in hospitalized children and is among the leading causes of childhood mortality worldwide. Detection of the HRV genome by reverse transcriptase-polymerase chain reaction and genomic sequencing has brought to light a new clade, HRV-C, to the already recognized HRV-A and HRV-B clades. The clinical complications related to all rhinovirus infections include acute otitis media, acute sinusitis, and acute bronchitis. The enormous public health implications from those diseases far overshadow those of the common cold. This article provides an overview of the pathogenesis of rhinovirus infection in the upper airways. Most research has been done in young healthy adults with self-limiting experimental and natural rhinovirus infections, and this may set the stage for understanding rhinovirus infections in the ear, sinus, and lower airways.
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PMID:Rhinovirus infections in the upper airway. 2136 25

Fever of unknown origin in patients with common variable immune deficiency (CVID) can be caused by variety of infectious, autoimmune, or malignancy-related etiologies. We present a 52-year-old man with history of CVID, who presented with 3 weeks of persistent high-grade fevers. During admission, he developed severe pancytopenia with shock and multiorgan failure. An extensive workup was performed for typical and atypical infections, autoimmune pathologies, and malignancy. His peripheral blood smear showed marked anisocytosis and poikilocytosis with elevated atypical lymphocytes. Flow cytometry showed markedly elevated CD8 counts, with abnormal CD4/CD8 ratio. Monospot test was negative but real-time polymerase chain reaction showed high Epstein-Barr virus load. Initial clinical suspicion was high for bacterial infections including pneumonia and acute sinusitis complicated by bacteremia and sepsis. Hematologic malignancy was also high on the differentials because of presence of rapidly progressive pancytopenia. The final diagnosis in this case illustrates a rare but potentially fatal disease that can present in CVID patients with persistent fevers and pancytopenia and can be refractory to standard treatment regimen. Because allergy and immunology physicians commonly treat CVID patients, they should be aware of this disease condition including pathophysiology, clinical presentation, laboratory workup, and treatment options.
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PMID:High-grade fever and pancytopenia in an adult patient with common variable immune deficiency. 2443 2

Streptococcus pneumoniae is a Gram-positive bacterium, causing acute sinusitis, otitis media, and severe diseases such as pneumonia, bacteraemia, meningitis and sepsis. Here we identify elongation factor Tu (Tuf) as a new Factor H binding protein of S. pneumoniae. The surface protein PspC which also binds a series of other human immune inhibitors, was the first identified pneumococcal Factor H binding protein of S. pneumoniae. Pneumococcal Tuf, a 55 kDa pneumococcal moonlighting protein which is displayed on the surface of pneumococci, is also located in the cytoplasm and is detected in the culture supernatant. Tuf binds the human complement inhibitors Factor H, FHL-1, CFHR1 and also the proenzyme plasminogen. Factor H and FHL-1 bound to Tuf, retain their complement regulatory activities. Similarly, plasminogen bound to Tuf was accessible for the activator uPA and activated plasmin cleaved the synthetic chromogenic substrate S-2251 as well as the natural substrates fibrinogen and the complement proteins C3 and C3b. Taken together, Tuf of S. pneumoniae is a new multi-functional bacterial virulence factor that helps the pathogen in complement escape and likely also in ECM degradation.
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PMID:Tuf of Streptococcus pneumoniae is a surface displayed human complement regulator binding protein. 2504 56

Cryptococcal infections are responsible for significant morbidity and mortality in immunocompromised patients. Reports of these infections in patients on small molecular kinase inhibitors have not been widely reported in clinical trials. We describe one case of cryptococcal meningoencephalitis and one case of cryptococcal pneumonia in two patients who were receiving ibrutinib for chronic lymphocytic leukemia. Despite different sites of cryptococcal infection, both patients had similar presentations of acute illness. Patient 1 was worked up for health care-associated pneumonia, as well as acute sinusitis prior to the diagnosis of cryptococcal meningoencephalitis. He also had a more complex past medical history than patient 2. Patient 2 developed atrial fibrillation from ibrutinib prior to admission for presumed health care-associated pneumonia. Cryptococcal antigen testing was done sooner in this patient due to patient receiving high-dose steroids for the treatment of underlying hemolytic anemia. We conclude that patients who develop acute illness while receiving ibrutinib should be considered for cryptococcal antigen testing.
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PMID:Cryptococcal infections in two patients receiving ibrutinib therapy for chronic lymphocytic leukemia. 2934 53

Most antibiotics are prescribed in primary care, and commonly for respiratory tract infections (RTIs). Narrow-spectrum phenoxymethylpenicillin is the antibiotic of choice for RTIs in the Scandinavian countries, while broader spectrum amoxicillin is used in most other European countries. This review summarizes the knowledge of the effect of phenoxymethylpenicillin versus amoxicillin for infections treated in ambulatory care. We searched PubMed/Medline and Embase for trials comparing the clinical effect of phenoxymethylpenicillin and amoxicillin. The Norwegian Knowledge Centre for the Health Services' checklist was used to assess risk of bias. In total, 1687 studies were identified, and 18 of these fulfilled the inclusion criteria. One additional study was found as a reference. The randomized controlled trials revealed no significant differences in clinical effect in acute sinusitis (three RCTs), GAS tonsillitis (11 RCTs) and Lyme borreliosis (two RCTs). One RCT on community-acquired pneumonia found amoxicillin to be superior, while the results were conflicting in the two RCTs on acute otitis. The results suggest that non-Scandinavian countries should consider phenoxymethylpenicillin as the treatment of choice for RTIs because of its narrower spectrum. More studies should be conducted on the clinical effect of phenoxymethylpenicillin versus amoxicillin for acute otitis and lower RTIs.
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PMID:Phenoxymethylpenicillin Versus Amoxicillin for Infections in Ambulatory Care: A Systematic Review. 3018 20

Objects: This meta-analysis aims to assess the efficacy and safety of high-dose, short-dose levofloxacin in comparison with conventional therapy on treating acute bacterial infection. Methods: PubMed, Embase and Cochrane database were searched up to September 2018. Only randomized controlled trials (RCTs) evaluating high-dose, short-course levofloxacin and conventional regimen in the treatment of acute bacterial infection were included. The primary outcomes were clinical responses, microbiologic eradication and adverse effects. Results: Seven RCTs of 3,731 patients (1,835 in the high-dose, short-course levofloxacin regimen group and 1,896 in the conventional regimen group) were included. Overall, no significant difference between the high-dose, short-course levofloxacin regimen group and the conventional regimen was found in terms of clinical response (risk ratio, RR: 1.01; 95%CI: 0.98-1.04, I 2=10%). In addition, the high-dose, short-course levofloxacin regimen had a similar microbiological eradication rate to conventional regimen (RR: 1.02; 95%CI: 0.98-1.06, I 2=0%). Moreover, the high-dose, short-course levofloxacin regimen had a similar incidence of treatment-emergent adverse events to conventional regimen (RR: 1.07; 95%CI: 0.99-1.17, I 2=0%). This trend was not affected by the different types of infections-community-acquired pneumonia, complicated urinary tract infection/acute pyelonephritis or acute sinusitis, different conventional regimen-levofloxacin (500 mg daily for 7-14 days) or ciprofloxacin (400 mg IV or 500 mg oral, twice daily for 10 days). Conclusion: High-dose, short-course levofloxacin exhibits similar clinical success and microbiologic eradication rates with conventional regimen in the treatment of acute bacterial infection. Moreover, the high-dose, short-course levofloxacin regimen was well tolerated and had comparable safety profiles with the conventional regimen.
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PMID:Comparison of high-dose, short-course levofloxacin treatment vs conventional regimen against acute bacterial infection: meta-analysis of randomized controlled trials. 3119 Sep 23

This chapter discusses various drugs for human influenza A (H5N1) and multidrug-resistant mycobacterium tuberculosis (MDR-TB). The H5N1 avian influenza does not presently meet the criteria of an antigenically shifted strain. It is presently an avian strain that has not undergone reassortment with a human strain and is not well adapted to humans. H5N1 isolates are resistant to the M2 inhibitors amantadine and rimantadine; these antivirals do not have a role for the treatment or prophylaxis against the strain. The neuraminidase inhibitors, oseltamivir and zanamivir, have in vitro activities against the human H5N1 isolates; however, recent data suggest that higher doses for longer periods may be required to be effective. Oseltamivir is an oral agent approved for prophylaxis and the treatment of influenza infections. Zanamivir is delivered topically to the respiratory tract with similar indications. The drugs discussed in the chapter for MDR-TB fall into three categories-quinolones, nitroimidazoles, and pyrroles. Drugs such as moxifloxacin are methoxyfluoroquinolones, which are already available and approved for the treatment of acute respiratory infections, such as community-acquired pneumonia, intra-abdominal infections, acute sinusitis, and skin infections. Gatifloxacin 5, is another methoxyfluoroquinolone that is in clinical development for tuberculosis treatment.
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PMID:Developing Infectious Disease Strategies for the Developing World. 3228 66


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