Streptococcus pneumoniae: Does Antimicrobial Resistance Matter?
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Over the past 3 decades, antimicrobial resistance among Streptococcus pneumoniae, the most common cause of community-acquired pneumonia (CAP), has escalated dramatically worldwide. In the late 1970s, strains of pneumococci displaying resistance to penicillin were described in South Africa and Spain. By the early 1990s, penicillin-resistant clones of S. pneumoniae spread rapidly across Europe and globally. Additionally, resistance to macrolides and other antibiotic classes escalated in tandem with penicillin resistance. Six international clones (serotypes 6A, 6B, 9V, 14, 19F, 23F) were responsible for most of these resistant isolates. Currently, 15 to 30% of S. pneumoniae worldwide are multidrug-resistant (MDR) (i.e., resistant to ≥ 3 classes of antibiotics). Despite the dramatic escalation in the rate of antimicrobial resistance among pneumococci worldwide, the clinical impact of antimicrobial resistance is difficult to define. Treatment failures due to antibiotic-resistant pneumococci have been reported with meningitis, otitis media, and lower respiratory tract infections, but the relation between drug resistance and treatment failures has not been convincingly established. Clinical failures often reflect factors independent of antimicrobial susceptibility of the infecting organisms. Host factors (e.g., extremes of age; underlying immunosuppressive or debilitating disease; comorbidities), or factors that affect intrinsic virulence of the organisms (e.g., capsular subtype) strongly influence prognosis. Mortality rates are higher in the presence of: multilobar involvement, renal insufficiency, need for intensive care unit (ICU) care, hypoxemia, severe derangement in physiological parameters, and comorbidities. Given these confounding factors, dissecting out the impact of antimicrobial resistance on clinical outcomes is difficult, if not impossible. Prospective, randomized trials designed to assess the clinical significance of antimicrobial resistance among pneumococci are lacking, and for logistical reasons, will never be done. Does in vitro resistance translate into clinical failures? Should changing resistance patterns modify our choice of therapy for CAP or for suspected pneumococcal pneumonia? In this review, we discuss several facets, including mechanisms of antimicrobial resistance among specific antibiotic classes, epidemiology and spread of antimicrobial resistance determinants regionally and worldwide, risk factors for acquisition and dissemination of resistance, the impact of key international clones displaying multidrug resistance, the clinical impact of antimicrobial resistance, and strategies to limit or curtail antimicrobial resistance among this key respiratory tract pathogen.It is generally assumed that the development of bacterial pneumonia becomes possible when the dose of inhaled or aspirated pathogens overwhelms the respiratory tract host defence system, but this hypothesis has not yet been tested either clinically or experimentally. This study evaluated inoculum dose in relation to onset of experimental pneumococcal pneumonia, and estimated the median effective dose resulting in pneumonia in healthy New Zealand White rabbits (mean± sd 4.75±0.25 kg (n = 27)). Rabbits were endobronchially inoculated with increasing doses of Streptococcus pneumoniae and pneumonia onset was observed over the following 96 h. The diagnostic approach was based on the Clinical Pulmonary Infection Score, modified for use in rabbits. Inoculation of S. pneumoniae at doses of >4.60 log 10 cfu made the development of pneumonia in rabbits more predictable (up to 90%). Lower doses of bacteria failed to cause pneumonia in 80% of inoculated animals. The median effective dose was estimated by means of logistical regression, probit analyses and the Reed–Muench method, and corresponded to 4.32, 4.38 and 4.67 log 10 cfu, respectively. It is speculated that development of pneumococcal pneumonia becomes more likely when the inoculum dose exceeds a threshold of antibacterial protection, making inoculum dose a risk factor for disease onset.
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Streptococcus pneumoniae is one of most common causes of community-acquired pneumonia. We evaluated a newly available rapid immunochromatographic test to detect S. pneumoniae in urine samples verifying its importance in the diagnosis of pneumococcal pneumonia. Our data, obtained from 104 patients with community-acquired pneumonia, show that Now S. pneumoniae Urinary Test is characterized by a sensitivity value of 77.7%, a specifity of 98.8%: positive and negative predictive values are 93.3% and 95.5%, respectively. In conclusion, Now S. pneumoniae Urinary Test should be a useful test to establish the etiology of community-acquired pneumonia.
Etiology
Pneumococcal pneumonia
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Following several signals indicating the inefficiency of the clinical treatment with various penicillin preparations in some cases, we decided to study the seric penicillin concentrations in the patients hospitalized in the "V. Babes" Hospital of Infectious Diseases, after administration of the various Romanian made forms of penicillin currently used in the therapy of streptococcal infections and in the prophylaxis of the sequelae of these infections. The data obtained on groups exceeding 30 persons by using two methods of determining the penicillin concentrations the dilutions and the diffusimetric methods revealed protective penicillin seric levels satisfactory for penicillin G and Efitard, according to the present treatment schemes. After 5 days from Moldamin administration only 45.4% of children and 43.3% of adults were found to have satisfactory penicillin concentrations. The administration of penicillin V reaches active penicillin concentrations in terms of the dose administered. The paper points out only one of the causes which together with others (such as beta-lactamase production and tolerance), contribute to the unsuccessful treatment with various forms of penicillin.
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Streptococcus pneumoniae is an important bacterial pathogen, especially for the very young and the very old (1). S. pneumoniae, also referred to as the pneumococcus, was formerly known as Diplococcus pneumoniae.
Pneumococcal infections
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Oral penicillin V gave higher and better sustained levels of penicillin activity in the plasma than oral buffered potassium penicillin G at each of 3 dosage levels, viz. 200000, 400000 and 1 million units. Intramuscular penicillin G yielded higher and better sustained levels than oral penicillin V in equivalent doses given at levels of 400000 or 1 million units. An i. m. dose of 200000 units of penicillin G produced higher peak levels and these occurred earlier but they were less well sustained than with this amount of oral penicillin V; the total amount of penicillin absorbed from this amount of penicillin was not significantly different for these 2 dosage forms. Persons over 60 years of age attained peak levels later; in general they had higher and better sustained levels of penicillin in the plasma from any given dose than did younger individuals.
Intramuscular injection
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Community-acquired pneumonia (CAP) is an important cause of morbidity and mortality in all age groups throughout the world. Bacterial pneumonia is the most described, with Streptococcus pneumoniae being the most important pathogen in all age groups. Viruses are also recognised as important causes of CAP both in children and adults. Viral pneumonia account for 13 - 50% of single pathogen diagnosed community-acquired pneumonia cases and 8 -27% of mixed bacterial-viral pneumonia.
Viral Pneumonia
Bacterial pneumonia
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Penicillin ointment mixtures have been observed to be effective in the treatment of certain local cutaneous infections.1However, topical therapy with penicillin is not so simple as it first would appear, since many factors affect such forms of penicillin therapy. In previous reports2the excellent sensitizing qualities of the penicillin per se or the penicillin mixture, the stability of the mixture and the diffusion of penicillin through the mixture were considered as some of the factors affecting treatment. In this report we should like to mention our initial experiences with the effect of the addition of an active therapeutic agent to the penicillin ointment mixture. Certain obvious qualifications are necessary for the consideration of additional therapeutic, as opposed to vehicular, agents to penicillin ointment mixtures. First, the substance should not inactivate penicillin. Second, the substance should increase the therapeutic quality of the ointment by extending the range of
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The dynamics of sensitivity to penicillin of staphylococcal populations in purulent inflammatory foci of patients treated and not treated with antibiotics was estimated according to 4 indices. No reliable differences in the dynamics of sensitivity to penicillin were found in 2 groups of the patients, when estimation was performed with respect to the frequency of the penicillin resistant or penicillin sensitive staphylococci and detection of the penicillin resistant staphylococci by direct inoculation of the focal excretion to the medium with penicillin. A reliable increase in the percentage of the penicillin resistant staphylococci in the microbial population was observed only in the patients treated with penicillin.
Penicillin resistance
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In this experiment, it is found that thhe addition of some compounds together with penicillin-G precursors into penicillin culture broth can increase or accelerate penicillin production, when compared with the single addition of penicillin G precursors. In these cases if the type of penicillin produced is chiefly penicillin G which is supposed to have been derived from penicillin G precursors, such compounds should be appreciated to improve the efficiency of penicillin G precursors. The authors have named such compounds “penicillin coprecursors” In this report, it is indicated that, among the adjuvants listed below, cystine has strong and cystein has weak coprecursor activity, but the other compounds no coprecursor activity._??_
Penicillin resistance
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