Streptococcus pneumoniae and beta-lactam antibiotic agents

Pneumococcus has been known for over 100 years. Despite an intensive research, the problem of pneumococcal diseases has not yet been solved. During the last few decades, the incidence of pneumococcal pneumonia has declined, but the S. pneumoniae is today the main, or one of the most frequent, causative agents of meningitis, sinusitis, otitis media and conjunctivitis. Besides, cases of pneumococcal appendicitis, tubo-ovarian abscess, haemolytico-uremic syndrome, cellulitis and urinary infections have been described. Therefore, it is very important from medical point of view to follow-up its sensitivity to antibacterial drugs. Unfortunately, during the latest decades, an increase in percentage of resistant clinical isolates has been registered. It is obvious that the investigation of the sensitivity of pneumococci, that is, of their resistance to beta-lactam antibiotics is essential. The examination of the interaction between pneumococci and penicillin has resulted in significant discoveries concerning the mechanism of the effect of penicillin as well as the impact of penicillin-binding proteins, lipoteichoic acid and choline-residues in the cell wall. A particular contribution as regards the effect of penicillin has been achieved by linking murein hydrolases (autolythic enzymes) with the expression of bactericidal effect of penicillin. Besides, the model of pneumococcal resistance to penicillin together with the model of meticillin resistance of staphylococci enabled the perception of the new mechanism of bacteria resistance to beta-lactam antibiotics. Given the pathogenic potential of pneumococci and the increase of clinical isolates resistant to antibiotics, it can be concluded that immunoprophylaxis is of great importance. Although several polyvalent vaccines are being used, there are still unsolved problems whose solution will improve the safety of their application, contribute to a better efficiency and enable a widespread application of antipneumococcal vaccines.     

Enhancing the relationship between physician and patient

We have studied the effects of zinc on the 51Cr survival of red blood cells (RBC) from patients with homozygous sickle cell anemia (SCA) using an animal model in which the RBC were transfused into specially prepared rats. The slope (lambdas) of a standard 51Cr RBC survival curve was used as a measure of the rate of RBC sequestration. The effects of intravenous zinc were of considerable therapeutic interest from the standpoint of setting guidelines for effective blood levels of zinc in patients. SCA RBC were transfused into rats whose plasma zinc levels had been raised 3-6 times above normal (300-600 mug/100 ml) by prior iv injection of zinc acetate; in three experiments the mean lambdas in zinc-treated animals breathing 15-16% oxygen was significantly lower (meaning lessened sequestration and greater survival) than saline-treated controls. A possible explanation for the requirement to lower ambient oxygen tension in order to see this zinc effect is discussed. We have further observed an increased mean lambdas for RBC from 10 SCA patients compared to 4 normal controls (0.134 vs 0.030; t = 2.8, p less than 0.01). The lambdas values are quite patient specific (4 patients studied; F = 18.2, P = 0.002). In vitro pretransfusion treatment of SCA RBC with 1.5 mM zinc resulted in a significant increase in hemoglobin oxygen affinity and a marked reduction in lambdas (0.073 vs 0.120; t = 4.5, p less than 0.01). The mean lambdas was not affected by in vitro 0.3 mM zinc treatment; this level did not change hemoglobin oxygen affinity. We conclude that systemic zinc therapy in the animal model described, at plasma levels only slightly higher than those presently obtained in patients, prolongs SCA RBC survival. This animal model is a sensitive measure of the sicklability of SCA RBC and is useful in the testing of in vitro and in vivo antisickling agents.     

Strategies in the treatment of penicillin-resistant Streptococcus pneumoniae

The epidemiology, resistance mechanisms, susceptibility testing, treatment, prevention, and clinical importance of penicillin-resistant Streptococcus pneumoniae (PRSP) infection are discussed. PRSP is an established presence in the United States, with some geographic areas reporting decreased susceptibility in up to half of isolates. The mechanism of resistance to beta-lactam antibiotics in S. pneumoniae is genetic changes resulting in decreased binding of drug to the bacterial cell wall. Emerging PRSP strains have necessitated testing as a tool in selecting drugs for treating life-threatening infections. Opinions differ on how to treat these infections empirically. Non-life-threatening infections, such as otitis media, are still often treated successfully with amoxicillin, amoxicillin-clavulanate potassium, or a third-generation cephalosporin. Currently recommended initial treatment of pneumococcal pneumonia in otherwise healthy patients requiring hospitalization consists of cefuroxime, ceftriaxone, or cefotaxime; some authors continue to emphasize injectable penicillin. Once the mainstay of empirical treatment of pneumococcal meningitis, penicillin has largely been abandoned in favor of cefotaxime or ceftriaxone. Vaccination remains an underutilized strategy in atrisk populations. The clinical importance of penicillin resistance among pneumococci is still uncertain. Changing patterns in the susceptibility of S. pneumoniae to penicillin make selection of appropriate therapy increasingly difficult. Key considerations are the site of infection and the level of resistance.     

Nursing staff between physician and patient

Departing from a report on today's understanding about nursing, the demanding duties nurses see themselves confronted with are featured in connection with the theme of this meeting. In a second part, difficulties in daily practise are treated. Furthermore, problematic aspects of collaboration within the nursing staff as well as between the disciplines burdening patients are covered. Possible improvements are proposed.     

Structural organization of the major autolysin from Streptococcus pneumoniae

LytA amidase is the best known bacterial autolysin. It breaks down the N-acetylmuramoyl-L-alanine bonds in the peptidoglycan backbone of Streptococcus pneumoniae and requires the presence of choline residues in the cell-wall teichoic acids for activity. Genetic experiments have supported the hypothesis that its 36-kDa chain has evolved by the fusion of two independent modules: the NH2-terminal module, responsible for the catalytic activity, and the COOH-terminal module, involved in the attachment to the cell wall. The structural organization of LytA amidase and of its isolated COOH-terminal module (C-LytA) and the variations induced by choline binding have been examined by differential scanning calorimetry and analytical ultracentrifugation. Deconvolution of calorimetric curves have revealed a folding of the polypeptide chain in several independent or quasi-independent cooperative domains. Elementary transitions in C-LytA are close but not identical to those assigned to the COOH-terminal module in the complete amidase, particularly in the absence of choline. These results indicate that the NH2-terminal region of the protein is important for attaining the native tertiary fold of the COOH terminus. Analytical ultracentrifugation studies have shown that LytA exhibits a monomer <--> dimer association equilibrium, through the COOH-terminal part of the molecule. Dimerization is regulated by choline interaction and involves the preferential binding of two molecules of choline per dimer. Sedimentation velocity experiments give frictional ratios of 1.1 for C-LytA monomer and 1.4 for C-LytA and LytA dimers; values that deviated from that of globular rigid particles. When considered together, present results give evidence that LytA amidase might be described as an elongated molecule consisting of at least four domains per subunit (two per module) designated here in as N1, N2, C1, and C2. Intersubunit cooperative interactions through the C2 domain in LytA dimer occur under all experimental conditions, while C-LytA requires the saturation of low affinity choline binding sites. The relevance of the structural features deduced here for LytA amidase is examined in connection with its biological function.     

A global gene pool for high-level cephalosporin resistance in commensal Streptococcus species and Streptococcus pneumoniae

Highly penicillin- and cephalosporin-resistant Streptococcus mitis and Streptococcus oralis were isolated in Spain, Hungary, and Berlin. With chromosomal DNA of these strains, resistant transformants of Streptococcus pneumoniae were obtained that expressed low-affinity variants of penicillin-binding proteins (PBPs) 2x, 1a, 2a, and 2b in different combinations, depending on the selective conditions. The transformants had cefotaxime MICs of up to 6 microg/mL, and those with a low-affinity PBP 2b were highly deficient in penicillin-induced lysis. Sequence analysis of the pbp2x genes confirmed the presence of a global gene pool of penicillin resistance determinants shared by commensal and pathogenic streptococci.     

Clonal relationships among high-level penicillin-resistant Streptococcus pneumoniae in the United States

Emu antibody responses to avian influenza virus (AIV) infection were evaluated by the competitive enzyme-linked immunosorbent assay (C-ELISA), agar gel immunodiffusion (AGID) and hemagglutination inhibition (HI) tests. All birds infected with AIV H5N1, H5N3, or H7N7 developed antinucleoprotein (NP) antibodies as early as 7 days postinfection as detected by the C-ELISA. The responses lasted 49 days for the emus receiving H5N3 and at least 56 days for emus receiving the other two viruses. By evaluating 50 emu field serum samples, the C-ELISA was found more sensitive than the AGID test for the detection of anti-NP antibodies. This study indicates that emus experimentally infected with AIV developed antibody responses that can be detected by C-ELISA, AGID, and HI tests. The results from this and our previous studies demonstrate the use of the C-ELISA as a substitute for the AGID test in a routine serodiagnostic screening for detection of antibodies to AIV infection in multiple avian species.     

Auditing the performance of the physician facing patient alcohol consumption

OBJECTIVE: To assess the Primary Care doctor's performance when faced with his/her patients' alcohol consumption. DESIGN: Retrospective evaluation of data on procedures by means of explicit normative criteria and implicit check-up of those not complying. SETTING: Urban health centre. PATIENTS: A random and institutionally based sample, over a week, of patients of both sexes who came for a general medical consultation (eleven blocks) without prior appointment. RESULTS: 110 clinical histories were evaluated. 60% were not asked about alcohol consumption. In the cases of those who were asked, the amount consumed was specified. Excessive consumption was recorded in the notes as a health risk factor in 87%. A liver profile was requested for 62%. Advice to give up or reduce alcohol consumption was given in all cases. CONCLUSIONS: Poor compliance with the assessment criteria chosen justifies the implementation of the corrective measures proper to quality control methodology. We underline the importance of generalizing the implementation of the Programme of Preventive Activities in Primary Care and the need to improve health professionals' training and motivation on the question.     

Surrogate disks for predicting cefotaxime and ceftriaxone susceptibilities of Streptococcus pneumoniae

Cefotaxime- and ceftriaxone-resistant Streptococcus pneumoniae is now appearing in some medical centers, but 30-micrograms cefotaxime or 30-micrograms ceftriaxone disks are not reliable for detecting such strains. Studies were undertaken to select another cephalosporin disk that might be used as a screening test that could be used in conjunction with a 1-micrograms oxacillin disk. A 30-micrograms cefuroxime disk is proposed: strains with zones > or = 28 mm in diameter are predictably susceptible to cefotaxime and ceftriaxone, and those with smaller zones should be further studied to confirm resistance to either drug. A 30-micrograms ceftizoxime disk may also be used as a screening test with zones > or = 26 mm indicating susceptibility, but cefuroxime disks are preferred.     

Acute mastoiditis in infants: penicillin-resistant Streptococcus pneumoniae and its therapy

Earlier studies in our laboratory showed that hydroxylated metabolites of polychlorinated biphenyls (PCBs), dibenzo-p-dioxins (PCDDs), and dibenzofurans (PCDFs) competitively inhibit thyroxine (T4) binding to transthyretin (TTR) and type I deiodinase (D1) activity. In this study, we investigated the possible inhibitory effects of hydroxylated metabolites of polyhalogenated aromatic hydrocarbons (PHAHs) on iodothyronine sulfotransferase activity. Rat liver cytosol was used as a source of sulfotransferase enzyme in an in vitro assay with 125I-labeled 3,3'-diiodothyronine (T2) as a model substrate. Increasing amounts of hydroxylated PCBs, PCDDs, or PCDFs or extracts from incubation mixtures of PHAHs and induced liver microsomes were added as potential inhibitors of T2 sulfotransferase activity. Hydroxylated metabolites of PCBs, PCDDs, and PCDFs were found to be potent inhibitors of T2 sulfotransferase activity in vitro with IC50 values in the low micromolar range (0.2-3.8 microM). The most potent inhibitor of T2 sulfotransferase activity in our experiments was the PCB metabolite 3-hydroxy-2,3',4, 4',5-pentachlorobiphenyl with an IC50 value of 0.2 microM. A hydroxyl group in the para or meta position appeared to be an important structural requirement for T2 sulfotransferase inhibition by PCB metabolites. Ortho hydroxy PCBs were much less potent, and none of the parent PHAHs was capable of inhibiting T2 sulfotransferase activity. In addition, the formation of T2 sulfotransferase-inhibiting metabolites of individual brominated diphenyl ethers and nitrofen as well as from some commercial PHAH mixtures (e.g., Bromkal, Clophen A50, and Aroclor 1254) was also demonstrated. These results indicate that hydroxylated PHAHs are potent inhibitors of thyroid hormone sulfation. Since thyroid hormone sulfation may play an important role in regulating free hormone levels in the fetus, and PCB metabolites are known to accumulate in fetal tissues after maternal exposure to PCBs, these observations may have implications for fetal thyroid hormone homeostasis and development.     

Neonatal hand abscess, osteomyelitis and meningitis caused by Streptococcus pneumoniae

Pathologic splenic rupture is a rare and life-threatening complication of acute leukemia. It is even more uncommon as the initial manifestation, and only a few cases has been reported in the literature. Early recognition of this complication is vital because the prognosis is fatal without immediate treatment by splenectomy. We report the case of a spontaneous spleen rupture irreversibly complicating the onset of acute lymphoblastic leukemia in a 19-year-old man, in spite of splenectomy. In our case abdominal ultrasound was a good, non-invasive diagnostic test. Therefore, we believe that the course of the underlying disease and the physical condition of the patient dramatically influenced the disease evolution.     

Effects of combination of benzylpenicillin and fosfomycin on penicillin-resistant Streptococcus pneumoniae

PURPOSE: To determine the effect of extent of peritoneal contamination in enteric abscesses on final outcome and duration of percutaneous drainage. PATIENTS AND METHODS: Results were retrospectively reviewed for 11 patients with varying degrees of peritoneal contamination secondary to subacute bowel perforation who were primarily treated with percutaneous drainage. Stepwise linear regression analysis of duration of drainage was performed with use of patient age and immune status, the site of bowel perforation, and the number of peritoneal compartments involved in the resultant contamination as independent variables. RESULTS: In 10 of 11 patients (91%) treatment of the resultant intraperitoneal collections with percutaneous drainage was successful irrespective of the extent of peritoneal contamination. There was no correlation between duration of drainage and extent of peritoneal contamination but good correlation with patient age and site of bowel perforation (r = 0.82, P = .02). CONCLUSION: In patients with enteric abscesses due to subacute bowel perforation, the duration of drainage and final outcome after percutaneous drainage are independent of the extent of peritoneal contamination.     

The emergency physician and patient confidentiality: a review

Confidentiality is a promise rooted in tradition, law, and medical ethics. Emergency physicians treat a variety of patients to whom confidentiality is of vital importance: employees, celebrities, victims of violence or disaster, minors, students, criminals, drug abusers, and patients with STDs. EDs should develop methods of ensuring confidentiality for all patients. Although confidentiality is an important principle that should be respected and guarded, it is not absolute. Various laws mandate disclosure of certain patient information; in addition, an overriding moral duty may occasionally require a breach of confidentiality. As Beauchamp and Childress noted, "the therapeutic role may sometimes have to yield to one's role as citizen and as protector of the interests of others." In general, however, circumstances requiring a breach of confidentiality are rare.     

Drug-resistant Streptococcus pneumoniae: the beginning of the end for many antibiotics?

The antiinflammatory activity of topically applied sertaconazole nitrate was investigated. The dermal administration of 2% sertaconazole to rats, in which edema was induced by application of croton oil in the external ear, induced a 39.8% reduction of edema. The results show that sertaconazole applied by topical route at the concentration at which it is used in clinic, has antiinflammatory action in this experimental model.     

Factors determining the quality of physician performance in patient care

The study determined the separate and joint effects of 1) physician specialty, 2) type of medical school attended, 3) time in practice, 4) type of ambulatory care setting, and 5) type of hospital on the quality of physician performance in patient care. The sample consisted of 454 physicians in 18 specialty categories. Multiple Classification Analysis was used to determine the effects of these predictors on the quality of physician performance. The study found that the organization of hospital care had a large independent effect, but that the other four predictors had relatively small effects on the quality of physician performance. The findings imply that the organization of the setting in which care is provided has more influence than the education and training that physicians had attained. All five predictors together explained 20 per cent of the variance. Methodological suggestions were made to improve the explanatory power of the variables, and various pragmatic for medical care administrators were presented.