Antimicrob Agents Chemother, 1999 May, 43(5), 1118 - 23 Pharmacodynamics of trovafloxacin, ofloxacin, and ciprofloxacin against Streptococcus pneumoniae in an in vitro pharmacokinetic model; Lister PD et al.; An in vitro pharmacokinetic model was used to simulate the pharmacokinetics of trovafloxacin, ofloxacin, and ciprofloxacin in human serum and to compare their pharmacodynamics against eight Streptococcus pneumoniae strains . The MICs of ofloxacin and ciprofloxacin ranged from 1 to 2 micrograms/ml . Trovafloxacin was 8- to 32-fold more potent, with MICs of 0.06 to 0.12 microgram/ml . Logarithmic-phase cultures were exposed to peak concentrations of trovafloxacin, ofloxacin, or ciprofloxacin achieved in human serum after 200-, 400-, and 750-mg oral doses, respectively . Trovafloxacin was dosed at 0 and 24 h, and ofloxacin and ciprofloxacin were dosed at 0, 12, and 24 h . Human elimination pharmacokinetics were simulated, and viable bacterial counts were measured at 0, 2, 4, 6, 8, 12, 24, and 36 h . Trovafloxacin was rapidly and significantly bactericidal against all eight strains evaluated, with viable bacterial counts decreasing at least 5 logs to undetectable levels . Times to 99.9% killing were only 1 to 3 h . Although the rate of killing with ofloxacin was substantially slower than that with trovafloxacin, ofloxacin was also able to eradicate all eight strains from the model, despite a simulated area under the inhibitory curve/MIC ratio (AUC/MIC) of only 49 . In contrast, ciprofloxacin eradicated only five strains (AUC/MIC = 44) from the model . Against the other three strains (AUC/MIC = 22), the antibacterial activity of ciprofloxacin was substantially diminished . These data corroborate clinical data and suggest that trovafloxacin has a pharmacodynamic advantage over ciprofloxacin and ofloxacin against S . pneumoniae in relation to its enhanced antipneumococcal activity. J Antimicrob Chemother, 1999 Mar, 43(3), 399 - 402 A study of susceptibility of 100 clinical isolates belonging to the Streptococcus milleri group to 16 cephalosporins; Aracil B et al.; The Streptococcus milleri group are uniformly susceptible to penicillin G, but their susceptibilities to different cephalosporins vary considerably . The antimicrobial susceptibilities of 100 clinically significant strains of the S . milleri group to 16 cephalosporins were determined by the agar dilution method . The majority of first-generation cephalosporins were highly active . Cefamandole, cefuroxime and cefprozil were the most active second-generation agents examined . Third-generation parenteral cephalosporins exhibited excellent activity, with the exception of ceftazidime . The most active of the oral preparations of this group was cefpodoxime, with cefixime and ceftibuten being considerably less active . MICs of cefepime, the only fourth-generation cephalosporin tested, were higher than those of cefotaxime and ceftriaxone. J Antimicrob Chemother, 1999 Mar, 43(3), 367 - 71 Efficacy of beta-lactam antibiotics combined with gentamicin against penicillin-resistant pneumococcal pneumonia in CBA/J mice; Tateda K et al.; We examined the efficacy of gentamicin combined with beta-lactam antibiotics against penicillin-resistant Streptococcus pneumoniae (PRSP) in a noncompromised mouse model of pneumonia . In the presence of 8 mg/L (0.25 x MIC) and 16 mg/L (0.5 x MIC) of gentamicin, MICs of penicillin G against 23 strains of PRSP decreased from 1-4 mg/L to 0.03 mg/L in 14 (61%) and 23 strains (100%), respectively . A short-time killing study using strain 741 showed that 8 mg/L of gentamicin (0.25 x MIC) increased the killing activity of penicillin G, cefotaxime and imipenem (at 0.25, 1 and 4 x MIC) during a 6 h incubation period . Survival studies showed that the combined treatment of penicillin-G (160 mg/kg) and gentamicin (10 mg/kg), which commenced 2 days after infection (twice a day for 5 days), provided complete protection, while no animal survived when either antibiotic was used alone . A significant improvement in mortality was observed when a small dose of imipenem (2.5 and 10 mg/kg) was used with gentamicin . Our results suggest that gentamicin, when combined with beta-lactam antibiotics, especially imipenem, may be potentially useful against PRSP pneumonia in noncompromised individuals. Biochem Biophys Res Commun, 1999 Apr 29, 258(1), 222 - 6 Expression of saliva-binding epitopes of the Porphyromonas gingivalis FimA protein on the surface of Streptococcus gordonii; Sharma A et al.; Porphyromonas gingivalis, a gram-negative oral anaerobic bacterium, has been implicated in the onset and development of periodontitis . The P . gingivalis fimbriae which mediate bacterial adherence to host oral sites and induce host inflammatory responses have been suggested as a potential antigen candidate . for vaccine development . This study was undertaken to generate Streptococcus gordonii vectors expressing the major subunit protein (FimA) of P . gingivalis fimbriae for testing as a potential live vaccine against periodontitis . We report here the expression of the C-terminal saliva-binding epitopes of P . gingivalis FimA on the surface of S . gordonii and demonstrate that domains containing free cysteine residues are poorly expressed on the surface of S . gordonii . Emerg Infect Dis, 1999 Mar-Apr, 5(2), 254 - 63 Rapid molecular genetic subtyping of serotype M1 group A Streptococcus strains; Hoe N et al.; Serotype M1 group A Streptococcus, the most common cause of invasive disease in many case series, generally have resisted extensive molecular subtyping by standard techniques (e.g., multilocus enzyme electrophoresis, pulsed-field gel electrophoresis) . We used automated sequencing of the sic gene encoding streptococcal inhibitor of complement and of a region of the chromosome with direct repeat sequences to unambiguously differentiate 30 M1 isolates recovered from 28 patients in Texas with invasive disease episodes temporally clustered and thought to represent an outbreak . Sequencing of the emm gene was less useful for M1 strain differentiation, and restriction fragment length polymorphism analysis with IS1548 or IS1562 as Southern hybridization probes did not provide epidemiologically useful subtyping information . Sequence polymorphism in the direct repeat region of the chromosome and IS1548 profiling data support the hypothesis that M1 organisms have two main evolutionary lineages marked by the presence or absence of the speA2 allele encoding streptococcal pyrogenic exotoxin A2. Emerg Infect Dis, 1999 Mar-Apr, 5(2), 235 - 40 Clonal differences among erythromycin-resistant Streptococcus pyogenes in Spain; Perez-Trallero E et al.; The aim of this study was to determine whether the high levels of erythromycin resistance in Streptococcus pyogenes found in Spain are due to the introduction and spread of one or more clones . Phenotypic and genotypic techniques were used to characterize all erythromycin-resistant S . pyogenes (ErR) isolated in Gipuzkoa, Spain, in the last 10 years and 128 ErR isolated in Vitoria and Madrid during 1996 . Of 437 ErR, 97% had the M phenotype; all 283 of the strains studied had the mefA determinant of resistance . After biotyping, T serotyping, emm typing, and genotyping, four major clones were detected . Clones B (biotype I, type T4, emm4, pulsed-field gel electrophoresis {PFGE} II) and D (biotype V, type T8.25, emm75, PFGE IV) comprised 78.8% of all ErR . The resistance of S . pyogenes to erythromycin was mainly due to an efflux mechanism of resistance (M phenotype); few clones were responsible for it. Am J Epidemiol, 1999 May 1, 149(9), 863 - 8 Group A Streptococcus carriage among close contacts of patients with invasive infections; Weiss K et al.; During the past few years, the incidence of invasive group A Streptococcus (GAS) infection has been increasing . However, there are presently no clear recommendations regarding antibiotic prophylaxis for close contacts of index patients . The aims of this study were 1) to determine the prevalence of carriage of the same GAS strain as the patient's among contacts of patients with invasive infections and 2) to assess the importance of exposure duration . From March 1995 to March 1996, the authors prospectively included in the study all patients with invasive GAS infection, as defined by the Working Group on Severe Streptococcal Infections, who came to Hopital Maisonneuve-Rosemont in Montreal, Quebec, Canada . An epidemiologic investigation was systematically carried out for each index case . Contacts were divided into two groups: those who had spent 24 hours or more with the index patient during the week preceding the beginning of his or her illness and those who had spent 12-24 hours with the index patient during that week . Strains of GAS were examined by serotyping (proteins M and T and the presence or absence of the serum opacity factor) and by characterization of streptococcal pyrogenic exotoxins (exotoxins A, B, and C) . One hundred and two contacts of 17 index cases with invasive GAS infection were systematically screened . Contacts were considered positive if they carried the same strain of the bacterium and the same streptococcal pyrogenic exotoxin as the index case . Among the contacts who had spent at least 24 hours per week with their respective index cases, 13 out of 48 (27%) were found to be harboring the same serotype of GAS as the index patient (95% confidence interval 14.5-39.5) . By comparison, only one of the 54 contacts in the 12- to 24-hour group (1.8%) was found to be carrying the same strain of the bacterium (95% confidence interval 0-5.3).This difference between the two groups was statistically significant (p<0.001) . The median age of the positive carriers (10 years) was significantly lower than the median age of the noncarriers (39 years) (p< or =0.0005) . This study showed that close contacts who had spent 12-24 hours with the index patient were rarely colonized with GAS . If antibiotic prophylaxis against GAS is recommended, it should probably target contacts who spent at least 24 hours with an infected patient during the week preceding illness onset. Heart, 1999 Jan, 81(1), 62 - 6 Urgent homograft aortic root replacement for aortic root abscess in infants and children; Chaturvedi R et al.; OBJECTIVE: To assess the results of early homograft aortic root replacement in infants and children with an aortic root abscess . DESIGN: Descriptive study of all patients with an aortic root abscess during 1987-97, identified by retrospective review of the echocardiographic and surgical registries . SETTING: A tertiary referral centre . PATIENTS: Five patients (age 0.6 to 13 years; two female) were identified with an aortic root abscess . Four had no known pre-existing congenital heart abnormality . Three had a misleading presentation and were referred to our hospital with non-cardiac diagnoses (fulminant hepatic failure; adult respiratory distress syndrome; cerebrovascular accident) . The other two presented with septicaemia and a murmur, respectively . Blood cultures identified Staphylococcus aureus (n = 3) and Streptococcus pneumoniae (n = 2) . Aortic root abscess was diagnosed by transthoracic echocardiography . Interventions: Homograft aortic root replacement with coronary reimplantation was performed urgently (median one day after diagnosis) . RESULTS: Four patients survived . The youngest died following multiorgan failure, multiple aortic fistulae, three valve involvement, and extensive tissue destruction preventing mitral valve replacement (S pneumoniae) . Two of the four survivors have required further surgery: mitral valve replacement (0.3 years later), and pulmonary autograft replacement of the homograft (8.3 years later) . All survivors remain in sinus rhythm and New York Heart Association functional class I . CONCLUSIONS: Infective endocarditis should be considered in any child with severe septicaemia or embolic phenomena . Echocardiographic diagnosis of an aortic root abscess indicates uncontrolled infection and impending haemodynamic collapse . Homograft aortic root replacement can be performed successfully in critically ill children with active infection. Microbiology, 1999 Apr, 145 ( Pt 4), 791 - 800 Biochemical and molecular analyses of the C-terminal domain of Era GTPase from Streptococcus pneumoniae; Zhao G et al.; Era, an essential GTPase, is present in many bacteria and Mycoplasma spp . and appears to play a major role in the cell cycle and other cellular processes . To further understand its function, an era gene from Streptococcus pneumoniae was identified and cloned, and a mutant era gene with a deletion of 68 codons from its 3'-terminus was constructed . The truncated Era protein was then purified and characterized, and the ability of the truncated era gene to complement an Escherichia coli mutant strain defective in Era production was examined . Like the full-length Era protein, the truncated Era protein was able to bind and hydrolyse GTP, but its binding activity was increased twofold and its hydrolytic activity was reduced sevenfold when compared with those of the full-length Era protein . Unlike the full-length Era protein, the truncated Era protein lost its ability to bind to the E . coli cytoplasmic membrane . The full-length era gene was able to complement the E . coli mutant deficient in Era production when carried on pACYC184, while the truncated era gene failed to do so when carried on pACYC184, pBR322 or pUC18 . The cellular amounts of the truncated Era and the full-length Era proteins in E . coli and S . pneumoniae, respectively, were then determined by Western blot analysis . In addition, the minimal amount of the S . pneumoniae Era protein needed for complementation of the E . coli mutant was also measured . Taken together, these results suggest that the C-terminus of the Era protein might be responsible for the binding of the protein to the cytoplasmic membrane and be essential for function. Microbiology, 1999 Apr, 145 ( Pt 4), 781 - 9 Molecular and genetic characterization of the capsule biosynthesis locus of Streptococcus pneumoniae type 23F; Morona JK et al.; The authors have previously reported the nucleotide sequence of the 5' and 3' portions of the Streptococcus pneumoniae type 23F capsular polysaccharide biosynthesis locus (cps23f) (from dexB to cps23fB and from cps23fL to aliA) . These regions of cps23f were very similar to the sequence reported for cps19f, the capsule locus of S . pneumoniae type 19F . However, Southern hybridization analysis indicated that no other genes closely related to cps19f are present in the cps23f locus . In this study long-range PCR was used to amplify and clone the section of the S . pneumoniae type 23F capsule locus between cps23fB and cps23fL . This region is 13 kb in size and contains 12 new ORFs, designated cps23fC-E, I, J, and T-Z . Functions are proposed for all of the protein products, including functional homologues of Cps19fC-E, Cps19fI and Cps19fJ . A biosynthetic pathway for type 23F capsular polysaccharide is also proposed. Scand J Immunol, 1999 Apr, 49(4), 417 - 23 Induction of phagocyte-stimulating and Th1-promoting cytokines by in vitro stimulation of human peripheral blood mononuclear cells with Streptococcus pneumoniae; Arva E et al.; Polymorphonuclear granulocytes, which provide a major defence against Streptococcus pneumoniae infections, are attracted to and activated by various cytokines . The aim of this study was to analyse the cytokine response of human peripheral blood mononuclear cells to stimulation with S . pneumoniae . Strains belonging to serogroups 4, 6, 14, 19 or 23, were isolated from nasopharynx, middle ear fluid, cerebrospinal fluid or blood . All strains induced a marked proliferative response of the peripheral blood mononuclear cells; the stimulatory index was 34+/-11 . High levels of pro-inflammatory cytokines were induced, i.e . interleukin (IL)-1beta (53+/-25 ng/ml), IL-6 (347+/-41 ng/ml) and tumour necrosis factor (TNF)-alpha (15+/-4 ng/ml) . Also, chemokines and immunoregulatory cytokines including IL-8 (215+/-224 ng/ml), IL-10 (122+/-60 pg/ml), IL-12 (1195+/-648 pg/ml), interferon (IFN)-gamma (18+/-4 ng/ml) and granulocyte macrophage colony-stimulating factor (135+/-80 pg/ml) were induced . Several of these cytokines can up-regulate phagocytosis and the killing of bacteria . Interestingly, strains isolated from middle ear fluid and blood elicited significantly fewer IL-8 and significantly more IL-12 and IL-10 than strains from nasopharynx . They also induced a stronger proliferative response . Our results indicate that pneumococci are potent inducers of cytokines, especially IL-12, favouring T-helper cell type 1 (Th1) responses. Eur J Clin Microbiol Infect Dis, 1999 Feb, 18(2), 120 - 5 Increase in penicillin resistance rates in Belgium due to clonal spread of a penicillin-resistant 23F Streptococcus pneumoniae strain; Hoefnagels-Schuermans A et al.; In 1994 a sudden increase in penicillin resistance was observed in Belgium among invasive pneumococci . To determine whether this increase was due to clonal spread of a resistant strain or to de novo acquisition of penicillin resistance, pneumococci of capsular types 23F, 19, 14, 9, and 6 isolated in 1993 and 1994, were analyzed by capsular serotyping and DNA macrorestriction analysis, resolved by pulsed-field gel electrophoresis . Furthermore, pneumococcal isolates from northern France, a region with a high prevalence of penicillin resistance, and from southern Belgium, a region with a low but increasing prevalence of penicillin resistance, were analyzed . The rate of resistance of invasive pneumococci to penicillin increased from 2.3% in 1993 to 7.6% in 1994 . Pneumococcal serotype 23F represented 26.7% of the penicillin-resistant isolates in 1993 and 40.4% in 1994, while the prevalence of serotype 23F decreased from 10.9% in 1993 to 8.8% in 1994 . In 1994 up to 35.8% of serotype 23F isolates were penicillin resistant . The Belgian penicillin-resistant 23F isolates from 1994 were genetically closely related to the French 23F penicillin-resistant isolates and, as clones were clearly distinct from the other serotypes as well as from the penicillin-susceptible 23F isolates . These data demonstrate the important contribution of the clonal spread of a penicillin-resistant pneumococcal strain in the overall increase of penicillin resistance in our country. Acta Otolaryngol, 1999 Jan, 119(1), 78 - 82 Effect of tumor necrosis factor alpha and interleukin 1-alpha on the adherence of Streptococcus pneumoniae to chinchilla tracheal epithelium; Tong HH et al.; The trachea whole organ perfusion technique was used to study the effect of tumor necrosis factor alpha (TNF alpha) and interleukin-1 alpha (IL-1 alpha) on the adherence of otitis media pathogen Streptococcus pneumoniae (Spn) type 6A . Tracheas were removed from chinchillas and divided equally . One-half trachea was activated by incubation with 1-10 ng/ml of either TNF alpha or IL-1 alpha prior to the addition of Spn 6A to the organ culture perfusion chamber . Colony forming units (cfu) of Spn/millimeter trachea were determined for activated tracheas and controls . Dose response and kinetics data were generated for each cytokine . The specificity of each reaction was determined by neutralization studies with specific anti-cytokine antibodies . The data indicate that both TNF alpha and IL-1 alpha increase the adherence of Spn to the respiratory epithelium of this tubal organ and suggest a mechanism which may facilitate enhanced adherence in vivo and thereby contribute to the pathogenesis of otitis media and other upper respiratory tract diseases. South Med J, 1999 Apr, 92(4), 400 - 3 Pleural fluid findings in patients with the acquired immunodeficiency syndrome: correlation with concomitant pulmonary disease; Soubani AO et al.; BACKGROUND: We sought to define the spectrum of conditions associated with pleural effusion (PE) in patients with the acquired immunodeficiency syndrome (AIDS) who submitted to diagnostic thoracentesis . METHODS: The medical records of patients with human immunodeficiency virus (HIV) infection and PE studied by thoracentesis over a 5-year period, were reviewed for demographics, clinical presentation, concomitant illnesses, pleural fluid analysis, management, and outcome . RESULTS: Thoracentesis was done in 30 patients, 24 men and 6 women, with an overall mean age of 36 +/- 9 years . Mean CD4 cell count was 157 +/- 249/mm3 . The cause of the PE was infectious in 21 (70%) and noninfectious in 9 (30%) . Bacterial pneumonia was the most common cause of PE (57%) . Streptococcus pneumoniae and Staphylococcus aureus were the major organisms recovered . Mycobacterial infections were present in 3 patients, and Nocardia sp was isolated from 1 patient . Non-Hodgkin's lymphoma (5 cases) was the leading noninfectious cause of PE, followed by Kaposi's sarcoma (3 cases) and adenocarcinoma of the lung (1 case) . Twelve of the 30 patients died during hospitalization . CONCLUSION: Pleural effusion is an important problem in patients with advanced HIV infection . It is most frequently associated with bacterial pneumonia . Cytologic and microbiologic examination of the pleural fluid is helpful in determining the cause of PE in this patient population. Endod Dent Traumatol, 1999 Feb, 15(1), 42 - 5 Antimicrobial effect of six endodontic sealers: an in vitro evaluation; Kaplan AE et al.; The aim of this study was to determine the in vitro antimicrobial effect of six endodontic sealers after 2, 20 and 40 days . The sealers studied were Apexit, Endion, AH26, AH-Plus . Procosol and Ketac Endo . The microorganisms used were Candida albicans, Staphylococcus aureus, Streptococcus mutans and Actinomyces israelii . Petri dishes were filled with sterile agar and 0.1-ml wells were prepared and filled with the sealers . The agar plates were stored for 24 h at 37 degrees C . The samples were then removed, immersed in 4.5 ml of culture medium and divided into three groups . The samples in group 1 were stored for 2 days at 37 degrees C whereas the samples of groups 2 and 3 were stored at 4 degrees C for 20 and 40 days respectively . The samples were then removed and discarded, and 0.1 ml of the culture medium was seeded on the agar plates in order to perform colony forming unit counts . Apexit, Endion and AH-Plus produced slight inhibition on Streptococcus mutans at 20 days and on Actinomyces israelii at every time interval . No effect was found on Candida albicans and Staphylococcus aureus . Ketac Endo only produced an antimicrobial effect on Actinomyces israelii at 2 and 40 days . AH26 and Procosol showed antimicrobial effect at 40 days on Candida albicans, at 20 and 40 days on Streptococcus mutans and Staphylococcus aureus, and an effective inhibition on Actinomyces israelii at every time interval . Statistical analysis revealed both sealers and microorganisms to be significant factors affecting results in groups 2 and 3 . In conclusion, the sealers evaluated in this study showed different inhibitory effects depending on time span . Overall, sealers containing cugenol and formaldehyde proved to be most effective against the microorganisms at the time intervals studied. J Bacteriol, 1999 May, 181(9), 2863 - 71 Regulation of expression of the fructan hydrolase gene of Streptococcus mutans GS-5 by induction and carbon catabolite repression; Burne RA et al.; The polymers of fructose, levan and inulin, as well as sucrose and raffinose, are substrates for the product of the fruA gene of Streptococcus mutans GS-5 . The purpose of this study was to characterize the DNA immediately flanking fruA, to explore the regulation of expression of fruA by the carbohydrate source, and to begin to elucidate the molecular basis for differential expression of the gene . Located 3' to fruA was an open reading frame (ORF) with similarity to beta-fructosidases which was cotranscribed with fruA . A transcriptional initiation site, located an appropriate distance from an extended -10-like promoter, was mapped at 165 bp 5' to the fruA structural gene . By the use of computer algorithms, two overlapping, stable stem-loop sequences with the potential to function as rho-independent terminators were found in the 5' untranslated region . Catabolite response elements (CREs), which have been shown to govern carbon catabolite repression (CCR) by functioning as negative cis elements in gram-positive bacteria, were located close to the promoter . The levels of production of fruA mRNA and FruA were elevated in cells growing on levan, inulin, or sucrose as the sole carbohydrate source, and repression was observed when cells were grown on readily metabolizable hexoses . Deletion derivatives containing fusions of fruA promoter regions, lacking sequences 5' or 3' to the promoter, and a promoterless chloramphenicol acetyltransferase gene were used (i) to demonstrate the functionality of the promoter mapped by primer extension, (ii) to demonstrate that CCR of the fru operon requires the CRE that is located 3' to the promoter region, and (iii) to provide preliminary evidence that supports the involvement of an antitermination mechanism in fruA induction. J Bacteriol, 1999 May, 181(9), 2840 - 5 Adherence of Staphylococcus aureus is enhanced by an endogenous secreted protein with broad binding activity; Palma M et al.; A novel mechanism for enhancement of adherence of Staphylococcus aureus to host components is described . A secreted protein, Eap (extracellular adherence protein), was purified from the supernatant of S . aureus Newman and found to be able to bind to at least seven plasma proteins, e.g., fibronectin, the alpha-chain of fibrinogen, and prothrombin, and to the surface of S . aureus . Eap bound much less to cells of Staphylococcus epidermidis, Streptococcus mutans, or Escherichia coli . The protein can form oligomeric forms and is able to cause agglutination of S . aureus . Binding of S . aureus to fibroblasts and epithelial cells was significantly enhanced by addition of Eap, presumably due to its affinity both for plasma proteins on the cells and for the bacteria. J Bacteriol, 1999 May, 181(9), 2773 - 81 Glycosyltransferase domain of penicillin-binding protein 2a from Streptococcus pneumoniae is membrane associated; di Guilmi AM et al.; Penicillin-binding proteins (PBPs) are bacterial cytoplasmic membrane proteins that catalyze the final steps of the peptidoglycan synthesis . Resistance to beta-lactams in Streptococcus pneumoniae is caused by low-affinity PBPs . S . pneumoniae PBP 2a belongs to the class A high-molecular-mass PBPs having both glycosyltransferase (GT) and transpeptide (TP) activities . Structural and functional studies of both domains are required to unravel the mechanisms of resistance, a prerequisite for the development of novel antibiotics . The extracellular region of S . pneumoniae PBP 2a has been expressed (PBP 2a*) in Escherichia coli as a glutathione S-transferase fusion protein . The acylation kinetic parameters of PBP 2a* for beta-lactams were determined by stopped-flow fluorometry . The acylation efficiency toward benzylpenicillin was much lower than that toward cefotaxime, a result suggesting that PBP 2a participates in resistance to cefotaxime and other beta-lactams, but not in resistance to benzylpenicillin . The TP domain was purified following limited proteolysis . PBP 2a* required detergents for solubility and interacted with lipid vesicles, while the TP domain was water soluble . We propose that PBP 2a* interacts with the cytoplasmic membrane in a region distinct from its transmembrane anchor region, which is located between Lys 78 and Ser 156 of the GT domain. Vaccine, 1999 Apr 9, 17(15-16), 1889 - 97 IgG subclass distribution of antibodies after vaccination of adults with pneumococcal conjugate vaccines; Soininen A et al.; The serum IgG subclass response of adults to Streptococcus pneumoniae (Pnc) capsular polysaccharides (PS) 6B, 14 and 23F was measured for four Pnc vaccines: the 23-valent PS vaccine or PS-protein conjugates with diphtheria toxoid (PncD), tetanus protein (PncT) or CRM197 protein (PncCRM) carriers . A standardized enzyme-linked immunosorbent assay specific for IgG subclasses was employed . This assay uses pneumococcal reference serum, lot 89-SF, to which anti-Pnc PS IgG subclass concentrations have been assigned . Both IgG1 and IgG2 responses were more frequent and higher in the conjugate groups than in the PS group . IgG subclasses in subjects vaccinated with PS displayed similar IgG2 predominant distribution previously observed in both natural and vaccine-induced antibodies . Antibodies induced by PncT, however, had a significantly altered IgG2/IgG1 ratio (P < 0.05), with a higher proportion of IgG1. Lancet, 1999 Apr 10, 353(9160), 1216 - 21 Prospective multicentre hospital surveillance of Streptococcus pneumoniae disease in India . Invasive Bacterial Infection Surveillance (IBIS) Group, International Clinical Epidemiology Network (INCLEN) Outpatient management of acute promyelocytic leukemia after consolidation chemotherapy. Dipartimento di Biotecnologie Cellulari ed Ematologia, University La Sapienza, Rome, ItalyThe feasibility and safety of outpatient management of acute promyelocytic leukemia (APL) during the aplastic phase after intensive consolidation chemotherapy, the incidence and types of complications requiring readmission to hospital, and the number of hospital days spared by this policy have been prospectively evaluated . After chemotherapy administration, patients were evaluated on an ambulatory basis . In the event of any complication they referred to the Emergency Unit (EU) of our Department dedicated to outpatients with hematologic diseases . Forty patients with APL observed over a 4 year period were eligible for intensive chemotherapy . After the achievement of complete remission they received a total of 104 consolidation courses and in 98 instances they were followed on an ambulatory basis . There were 41 cases (42%) of rehospitalization for fever (40 cases) or severe anemia (one case) . Only one patient died due to a brain hemorrhage . Streptococcus viridans was the organism most frequently isolated from blood . Empiric once-a-day antibacterial therapy with ceftriaxone and amikacin was effective in 87% of the cases and made possible early discharge in 28% of the cases to continue the antibiotic therapy on an outpatient setting . Patients were managed out of the hospital for 76% of the post-consolidation neutropenia period . Thanks to the availability of an EU specifically dedicated to outpatients with hematologic diseases, out-hospital management of APL patients after consolidation therapy appeared to be safe, well accepted, potentially cost-saving, and contributed to saving the risk of developing severe nosocomial infections. Kansenshogaku Zasshi, 1999 Feb, 73(2), 163 - 71 {In vitro susceptibility of Streptococcus agalactiae clinical isolates to beta-lactam antibiotics}; Ikeda N et al.; The susceptibility of Streptococcus agalactiae (S . agalactiae) clinical isolates of Juntendo University Urayasu Hospital, and type strain ATCC 13813 to beta-lactam antimicrobial agents was evaluated by means of macro-broth dilution MIC determination, killing kinetics and population analysis . When 10(6) cells of S . agalactiae were inoculated and cultured in Todd-Hewitt broth containing two-fold serial dilutions of penicillin, the viable cell count showed that about 10(2) cells survived irrespective of the penicillin concentration which ranged from 0.063 to 128 micrograms/ml . The result indicated that S . agalactiae had tolerance to penicillin (MICs were around 0.063 microgram/ml) . Furthermore, the S . agalactiae strains were found to have a paradoxical response to penicillin in an acidic condition (pH 5.5) . When the cell counts were performed at pH 5.5, about 10(2) cells survived at penicillin concentrations from 0.016 to 0.125 microgram/ml, while about 10(4) cells survived at the concentrations of 1 to 8 micrograms/ml . The antibiotic tolerance and paradoxical effects of S . agalactiae were also observed in killing kinetics . The ATCC 13,813 and 10 out of 11 clinical strains showed slow response to penicillin-mediated killing at pH 7.8 and ATCC 13,813 and one of the clinical strains showed a reduced response with increase in penicillin concentration at pH 5.5 . These results suggested that the tolerance and paradoxical effect of S . agalactiae cells to beta-lactam antibiotics may be one of the reasons for frequent re-colonization of S . agalactiae at the time of delivery after the chemophylaxis in the 2nd trimester. Am J Kidney Dis, 1999 May, 33(5), 927 - 33 Hospitalization in peritoneal dialysis patients; Fried L et al.; Hospitalization rates are declining more rapidly for peritoneal dialysis (PD) than for hemodialysis patients . This has been postulated to be caused in part by lower peritonitis rates . However, the causes of admission have not been reexamined in the setting of declining rates . We prospectively examined our hospitalization rates, causes of admission, and impact of peritonitis on hospitalization in adult PD patients at a single center over a 4-year period . There were 274 admissions in 168 patient-years for a rate of 1.6 admissions and 13.0 hospital days per patient-year . Rates were greater for men (1.8 v 1.5; P = 0.013), patients with diabetes (2.2 v 1.4, P < 0.001), and those with a higher peritoneal equilibration test result . Creatinine clearance and sex were independent predictors in a multivariate analysis . The most common causes for admission were cardiac disease (14.6%) and peritonitis (13.5%) . Peritonitis accounted for 0.21 admissions and 2.0 hospital days per patient-year . Thirty percent of the incident patients were admitted during the first 90 days of dialysis . Admissions for dehydration and glucose abnormalities were more common in the first 90 days . Overall admission rates, as well as admission rates for peritonitis, did not change over time, although hospital days per year decreased . Those admitted for peritonitis had higher peritonitis rates, more time on PD, and were more likely to be black . Eighty-one percent of the admissions for peritonitis were caused by Staphylococcus aureus, Streptococcus spp, or gram-negative/fungal peritonitis . Patients with peritonitis caused by Staphylococcus epidermidis were less likely to be admitted than patients with peritonitis caused by other organisms . To conclude, peritonitis remains a common cause of hospitalization, despite low peritonitis rates . To decrease admissions for peritonitis, attention should be focused on preventing peritonitis caused by organisms other than S epidermidis. Equine Vet J, 1999 Mar, 31(2), 160 - 8 Investigations on the ability of clenbuterol hydrochloride to reduce clinical signs and inflammation associated with equine influenza A infection; Kastner SB et al.; Twenty-four Quarter Horse and Quarter Horse-cross yearlings were experimentally infected with influenza A virus (Influenza A/equine/Saskatoon/90 {H3N8}) by nebulisation . In a double blind controlled trial the horses were randomly assigned to 3 groups of 8 animals . Group 1 received a placebo, (carrier syrup), Group 2 the labelled dose and Group 3 twice the labelled dose of clenbuterol hydrochloride . All treatments were given per os b.i.d . for 10 days and started on the day of infection . The horses were monitored for clinical signs of influenza infection for 14 days . Bronchoalveolar lavages were performed 4 days prior to, and 5 and 13 days after infection . Cell counts and concentrations of prostaglandin E2 and prostaglandin F2alpha in the lavage fluid were determined . Blood samples for haematology and serology were taken 4 days before, on the day of infection, 5, 9 and 13 days after infection . All horses experienced a typical influenza infection with fever, coughing and secondary bacterial infections with mainly Actinobacillus spp . and Streptococcus spp . There was no statistically or clinically significant effect of treatment with clenbuterol hydrochloride on measured clinical or laboratory parameters within 14 days of infection. Hinyokika Kiyo, 1999 Feb, 45(2), 103 - 5 {A case of multiloculated retroperitoneal abscess successfully treated by percutaneous drainage with a Malecot catheter}; Ishizu K et al.; Percutaneous catheter drainage offers an attractive alternative to open surgical drainage as the first choice in the treatment of retroperitoneal abscess . However, multiloculated abscess is difficult to drain percutaneously . We report a case of multiloculated retroperitoneal abscess successfully treated by percutaneous drainage with a Malecot catheter . A 47-year-old woman complained of fever and left flank pain . The peripheral while blood cell count was 16,800/mm3 and the blood sugar was 369 mg/dl . The computer tomographic (CT) scan showed a large multiloculated mass in the left retroperitoneum . An aspiration needle was inserted into the perinephric mass under ultrasonographic guidance . The definitive diagnosis of abscess was made by aspiration of purulent fluid . A 20 Fr . Malecot catheter was passed over the guide wire under fluoroscopic guidance . Two hundred ml of pus was smoothly aspirated . Streptococcus agalactiae was isolated from the aspirate . Antibiotics and insulin were started . The catheter was retained for 49 days until ultrasonography revealed disappearance of the abscess . One year later, she had no symptoms of recurrence. Diagn Microbiol Infect Dis, 1999 Apr, 33(4), 267 - 73 Comparison of MicroScan MICroSTREP, PASCO, and Sensititre MIC panels for determining antimicrobial susceptibilities of Streptococcus pneumoniae; Guthrie LL et al.; The MicroScan MICroSTREP MIC panel was compared with PASCO and Sensititre systems against 157 isolates of Streptococcus pneumoniae chosen to include penicillin-susceptible, intermediate, and resistant strains . Arbitration testing was performed by microbroth dilution using National Committee for Clinical Laboratory Standards guidelines . Overall essential agreement of 94-97% and categorical agreement of 91-94% with the reference method was achieved for the three systems . There were 8 very major errors (false susceptibility) for PASCO, 10 for Sensititre, and 9 for MICroSTREP; 4 major errors (false resistance) each for PASCO and MICroSTREP, and 6 for Sensititre . Most of these errors occurred with trimethoprim/sulfamethoxazole . Minor errors (susceptible or resistant versus intermediate) totaled 47 for PASCO, 69 for Sensititre, and 53 for MICroSTREP . Minor interpretive errors were most common with penicillin and ceftriaxone . This study showed that all three MIC panels provided interpretive results comparable to one another and to the reference method. Diagn Microbiol Infect Dis, 1999 Apr, 33(4), 255 - 60 Incidence of erythromycin resistance in Streptococcus pyogenes: a 10-year study; Betriu C et al.; We studied the evolution of susceptibility of Streptococcus pyogenes isolated in our hospital from 1987 to 1996 . Susceptibility to penicillin, ampicillin, cefotaxime, cefuroxime, imipenem, erythromycin, clindamycin, tetracycline, vancomycin, ciprofloxacin, rifampin, and chloramphenicol was determined by the National Committee for Clinical Laboratory Standards broth microdilution method . Differentiation of phenotypes of erythromycin-resistant strains was performed using the double-disc method . All isolates remained very susceptible in vitro to penicillin and all of the other beta-lactam agents tested . Between 1987 and 1995 the incidence of erythromycin resistant strains remained below 5%; the difference in the resistance rate between 1995 (2.6%) and 1996 (17.1%) was statistically significant . The macrolide resistance M phenotype was the most frequent . The isolation rates of tetracycline-resistant strains increased from 2.2% in 1987 to 11.2% in 1988 . The marked increase in the incidence of erythromycin resistance observed in our area warrants periodic surveillance of antibiotic susceptibility of S . pyogenes isolates and emphasizes the need to control outpatient antibiotics . The preponderance of the M phenotype may have implications in the choice of antibiotic. J Dairy Sci, 1999 Apr, 82(4), 712 - 9 Bacteria associated with clinical mastitis in dairy heifers; Waage S et al.; A 1-yr field investigation of clinical mastitis in heifers was carried out in 24 veterinary districts in Norway . Quarter lacteal secretions from cases that occurred prepartum or within 14 d postpartum were examined bacteriologically . The study included 1040 heifers with clinical mastitis, and the total number of quarters that were clinically affected was 1361 . The organisms that were most frequently isolated from samples from these quarters were Staphylococcus aureus (44.3%), Streptococcus dysgalactiae (18.2%), Staph . aureus together with Strep . dysgalactiae (1.2%), coagulase-negative staphylococci (12.8%), Arcanobacterium pyogenes (3.5%), A . pyogenes together with Strep . dysgalactiae (0.5%) or Staph . aureus (0.4%), and Escherichia coli (6.4%) . Of the coagulase-negative staphylococci, Staphylococcus simulans (53.7%), Staphylococcus hyicus (14.8%), and Staphylococcus chromogenes (14.8%) were the most prevalent species . Except for a higher relative percentage of A . pyogenes in cases that occurred before parturition (8.2%) than in cases that occurred after parturition (2.7%), no significant differences were observed in the distribution of the various organisms among prepartum and postpartum cases . Regional variations were observed in the distribution of organisms . The proportions of Staph . aureus and A . pyogenes were highest, and the proportion of coagulase-negative staphylococci was lowest, in late autumn and early winter . The proportion of E . coli was highest in summer . In heifers in which mastitis was associated with increased rectal temperature or other systemic signs, the proportion of clinically affected quarters that were infected with Staph . aureus was larger than that in heifers without systemic reaction. J Biol Chem, 1999 Apr 30, 274(18), 12537 - 43 Digestion of Streptococcus pneumoniae cell walls with its major peptidoglycan hydrolase releases branched stem peptides carrying proinflammatory activity; Majcherczyk PA et al.; The peptidoglycan of Gram-positive bacteria is known to trigger cytokine release from peripheral blood mononuclear cells (PBMCs) . However, it requires 100-1000 times more Gram-positive peptidoglycan than Gram-negative lipopolysaccharide to release the same amounts of cytokines from target cells . Thus, either peptidoglycan is poorly active or only part of it is required for PBMC activation . To test this hypothesis, purified Streptococcus pneumoniae walls were digested with their major autolysin N-acetylmuramoyl-L-alanine amidase, and/or muramidase . Solubilized walls were separated by reverse phase high pressure chromatography . Individual fractions were tested for their PBMC-stimulating activity, and their composition was determined . Soluble components had a Mr between 600 and 1500 . These primarily comprised stem peptides cross-linked to various extents . Simple stem peptides (Mr <750) were 10-fold less active than undigested peptidoglycan . In contrast, tripeptides (Mr >1000) were >/=100-fold more potent than the native material . One dipeptide (inactive) and two tripeptides (active) were confirmed by post-source decay analysis . Complex branched peptides represented </=2% of the total material, but their activity (w/w) was almost equal to that of LPS . This is the first observation suggesting that peptidoglycan stem peptides carry high tumor necrosis factor-stimulating activity . These types of structures are conserved among Gram-positive bacteria and will provide new material to help elucidate the mechanism of peptidoglycan-induced inflammation. J Biol Chem, 1999 Apr 30, 274(18), 12245 - 51 Purification and characterization of a novel cysteine proteinase (periodontain) from Porphyromonas gingivalis . Evidence for a role in the inactivation of human alpha1-proteinase inhibitor; Nelson D et al.; Periodontal disease is characterized by inflammation of the periodontium manifested by recruitment of neutrophils, which can degranulate, releasing powerful proteinases responsible for destruction of connective tissues, and eventual loss of tooth attachment . Although the presence of host proteinase inhibitors (serpins) should minimize tissue damage by endogenous proteinases, this is not seen clinically, and it has been speculated that proteolytic inactivation of serpins may contribute to progression of the disease . A major pathogen associated with periodontal disease is the Gram-negative anaerobe Porphyromonas gingivalis, and in this report, we describe a novel proteinase that has been isolated from culture supernatants of this organism that is capable of inactivating the human serpin, alpha1-proteinase inhibitor, the primary endogenous regulator of human neutrophil elastase . This new enzyme, referred to as periodontain, belongs to the cysteine proteinase family based on inhibition studies and exists as a 75-kDa heterodimer . Furthermore, periodontain shares significant homology to streptopain, a proteinase from Streptococcus pyogenes, and prtT, a putative proteinase from P . gingivalis . Clearly, the presence of this enzyme, which rapidly inactivates alpha1-proteinase inhibitor, could result in elevated levels of human neutrophil elastase clinically detected in periodontal disease and should be considered as a potential virulence factor for P . gingivalis. Arch Dis Child, 1998 Dec, 79(6), 510 - 3 Empyema thoracis: a role for open thoracotomy and decortication; Carey JA et al.; BACKGROUND: Thoracentesis and antibiotics remain the cornerstones of treatment in stage I empyema . The management of disease progression or late presentation is controversial . Open thoracotomy and decortication is perceived to be synonymous with protracted recovery and prolonged hospitalisation . Advocates of thoracoscopic adhesiolysis cite earlier chest drain removal and hospital discharge . This paper challenges traditional prejudice towards open surgery . METHODS: A five year audit of empyema cases referred to a regional cardiothoracic surgical unit analysing previous clinical course, surgical management, and outcome . RESULTS: Between February 1992 and February 1997, the number of referrals to this centre increased dramatically . Twenty-two children were referred for surgery (15 boys, seven girls; age range, 0.5-16 years) . Before referral, patients had been unwell for 6-50 days (median, 15), had been treated with several antibiotics, and had undergone chest ultrasound (15 patients), computed tomography (five patients), pleural aspiration attempts (13 patients), and intercostal drainage (seven patients) . The organism responsible was identified in only two cases (Streptococcus pneumoniae) . Three patients had intraparenchymal abscess formation . Eighteen patients underwent open thoracotomy and decortication . Drain removal was performed on the first or second day . Fever resolved within 48 hours . Median hospital stay was four days . All patients had complete clinical and radiological resolution . CONCLUSIONS: Treatment must be tailored to the disease stage . In stage II and III diseases, open decortication followed by early drain removal results in rapid symptomatic recovery, early hospital discharge, and complete resolution . In the early fibrinopurulent phase, alternative strategies should be considered . However, even in ideal cases, neither fibrinolysis nor thoracoscopic adhesiolysis can achieve more rapid resolution at lower risk. Eur J Neurol, 1999 Jan, 6(1), 87 - 9 Brucellar spinal epidural abscess; Pina MA et al.; Spinal epidural abscesses account for approximately one of every 10, 000 admissions to tertiary hospitals . The midthoracic vertebrae are the most frequently affected, whilst the cervical spine is involved in fewer patients . Staphylococcus aureus is identified as the cause in most cases of epidural abscess; other bacteria responsible include Gram-negative bacteria, Streptococcus species and Brucella species . We report the case of a patient with cervical spondylodiscitis at level C4-C5 and an epidural abscess which was compressing the spinal cord and the retropharyngeal space . The previous symptoms of brucellosis were atypical . We discuss the clinical manifestations, diagnosis, treatment and prognosis of the case . N Z Med J, 1999 Mar 12, 112(1083), 74 - 8 Antibiotic susceptibility of Streptococcus pneumoniae in New Zealand; Brett W et al.; AIMS: To determine the current antibiotic susceptibility patterns of Streptococcus pneumoniae from four centres in New Zealand . METHODS: Over a six-month period in 1997, 386 consecutive clinical isolates of S pneumoniae were collected by four laboratories (Auckland, Wellington, Hamilton and Christchurch) from general practice or inpatients . Susceptibility testing for seven antibiotics was performed by each centre using the Etest . RESULTS: Eighty-three-percent of isolates were penicillin susceptible, 12% showed intermediate resistance to penicillin and 5% were penicillin resistant . Overall, 93 and 91% of isolates were susceptible to amoxicillin/clavulanic acid and ceftriaxone, respectively . Erythromycin and tetracycline had similar rates of susceptibility (88 and 87%, respectively) . Resistance to cotrimoxazole was common, with only 57% of isolates susceptible to this combination . No National Committee for Clinical Laboratory Standard (NCCLS) breakpoints were available for cefaclor to allow interpretation of the minimum inhibitory concentration data for this agent . Wellington had lower resistance rates than Auckland, Christchurch and Hamilton . Isolates from children had consistently higher resistance rates (two- to five-fold greater for beta-lactams and 1.2 to 1.3-fold for other agents) compared with isolates from adult patients . CONCLUSIONS: Resistance to multiple antibiotics among S pneumoniae is now evident in New Zealand, although rates varied between study centres . The overall rate of penicillin resistance is 5%, which is similar to that observed in many European and US cities but lower than the rates reported in badly affected areas (> 30%) . These data suggest that amoxicillin (+/- clavulanic acid), erythromycin or tetracycline are appropriate agents for empirical use in less serious community acquired infections when S pneumoniae is suspected . Ceftriaxone, with or without vancomycin, should be considered in the empirical treatment of invasive, disease until sensitivities are known. Carbohydr Res, 1998 Dec 15, 313(3-4), 165 - 74 Structure of the enzymatically synthesized fructan inulin; Heyer AG et al.; Construction, purification and characterization of a fusion protein of maltose-binding protein of Escherichia coli and the fructosyltransferase of Streptococcus mutans is described . With the purified protein, in vitro synthesis of inulin was performed . The obtained polysaccharide was characterized by high-performance size-exclusion chromatography (HPSEC) and static light scattering (SLS) in dilute aqueous and dimethyl sulfoxide solution . For all samples very high molecular weights between 60 x 10(6) and 90 x 10(6) g/mol and a remarkable small polydispersity index of 1.1 have been determined . Small root-mean-square radii of gyration point to a compact conformation in dilute solution . No difference between native and enzymatically synthesized inulin was observed by X-ray powder diffraction and thermoanalysis of solid samples. Clin Exp Immunol, 1999 Apr, 116(1), 100 - 6 Superantigen-induced T cell responses in acute rheumatic fever and chronic rheumatic heart disease patients; Bhatnagar A et al.; CD4+ and CD8+ T cells from healthy donors, acute rheumatic fever (ARF) and chronic rheumatic heart disease (CRHD) patients responded variably to a superantigen from Streptococcus pyogenes--Streptococcal pyrogenic erythrogenic toxin A (SPE-A) . In vitro culture of CD4+ T cells from ARF patients (CD4-ARF) with SPE-A exhibited a Th1 type of response as they produced high levels of IL-2, while CD4+ T cells from CRHD patients (CD4-RHD) secreted IL-4 and IL-10 in large amounts, i.e . Th2 type of cytokine profile . The skewing of human CD4+ T cells (in response to SPE-A stimulation) to Th1 or Th2 type reflects the role of the two subsets in a disorder with differing intensities at the two extremes of the spectrum . Moreover, the anergy induction experiments revealed that CD8-ARF and CD8-RHD undergo anergy (to different extents), whereas CD4+ T cells do not, in response to re-stimulation by SPE-A . These results initially demonstrate that both CD4+ and CD8+ T cells respond differentially to SPE-A, and hence it is an important observation with respect to the pathogenesis of ARF/CRHD . Anergy in CD8+ T cells in the presence of SPE-A in vitro goes a step further to show the clinical relevance of these cells and their possible role in suppression of the disease. Cerebrovasc Dis, 1999 May-Jun, 9(3), 182 - 4 Subarachnoid hemorrhage due to septic embolic infarction in infective endocarditis; Krapf H et al.; During antibiotic therapy, a 56-year-old man with a Streptococcus bovis endocarditis developed an infarction of the right middle cerebral artery (MCA) . Thirty hours after stroke onset, cranial computed tomography controls demonstrated a secondary subarachnoid hemorrhage, marked in the cistern of the right MCA . The latent period, cerebrospinal fluid analysis, angiographic and pathologic findings favor the assumption of a pyogenic arterial wall necrosis of the MCA due to a septic embolus . This pathomechanism of intracranial hemorrhage in infective endocarditis should be distinguished from a rupture of a mycotic aneurysm. J Exp Med, 1999 Apr 19, 189(8), 1217 - 28 Presentation of antigen in immune complexes is boosted by soluble bacterial immunoglobulin binding proteins; Leonetti M et al.; Using a snake toxin as a proteic antigen (Ag), two murine toxin-specific monoclonal antibodies (mAbs), splenocytes, and two murine Ag-specific T cell hybridomas, we showed that soluble protein A (SpA) from Staphylococcus aureus and protein G from Streptococcus subspecies, two Ig binding proteins (IBPs), not only abolish the capacity of the mAbs to decrease Ag presentation but also increase Ag presentation 20-100-fold . Five lines of evidence suggest that this phenomenon results from binding of an IBP-Ab-Ag complex to B cells possessing IBP receptors . First, we showed that SpA is likely to boost presentation of a free mAb, suggesting that the IBP-boosted presentation of an Ag in an immune complex results from the binding of IBP to the mAb . Second, FACS analyses showed that an Ag-Ab complex is preferentially targeted by SpA to a subpopulation of splenocytes mainly composed of B cells . Third, SpA-dependent boosted presentation of an Ag-Ab complex is further enhanced when splenocytes are enriched in cells containing SpA receptors . Fourth, the boosting effect largely diminishes when splenocytes are depleted of cells containing SpA receptors . Fifth, the boosting effect occurs only when IBP simultaneously contains a Fab and an Fc binding site . Altogether, our data suggest that soluble IBPs can bridge immune complexes to APCs containing IBP receptors, raising the possibility that during an infection process by bacteria secreting these IBPs, Ag-specific T cells may activate IBP receptor-containing B cells by a mechanism of intermolecular help, thus leading to a nonspecific immune response. Res Vet Sci, 1999 Apr, 66(2), 93 - 9 Pulsed-field gel electrophoresis and distribution of the genes zag and fnz in isolates of Streptococcus equi; Lindmark H et al.; Streptococcus equi subsp . equi and subsp . zooepidemicus are important pathogens of the equine respiratory tract . Isolates of both subspecies were examined by pulsed-field gel electrophoresis (PFGE) . With the exception of eight isolates, a unique band pattern was displayed for each of the 48 subsp . zooepidemicus isolates tested . A method to distinguish isolates of the genetically very homogeneous subsp . equi has hitherto not been available, although several methods have been tested . By the use of PFGE, 50 isolates of subsp . equi could be divided into eleven groups, each with a unique pulsotype . In addition, the recently characterised genes encoding the cell-wall proteins ZAG and FNZ of S . equi subsp . zooepidemicus strain ZV were shown by Southern blots to be present in all 98 tested isolates, including the type strains of the two subspecies . Binding assays showed that the expression of the two genes clearly differentiate between the two subspecies . J Chemother, 1999 Feb, 11 Suppl 1, 35 - 43 Evolving resistance patterns of Streptococcus pneumoniae: a link with long-acting macrolide consumption? Baquero F. The Alexander Project indicates an increase in the prevalence of S . pneumoniae resistance to macrolide antibiotics . In some centers, the prevalence of S . pneumoniae macrolide resistance exceeds that of penicillin resistance . Centers with a high level of macrolide resistance tend to also have high levels of penicillin resistance . Antimicrobial use may be an important driver of resistance . The application of pharmacodynamic concepts suggests that bacterial exposure to low and prolonged concentrations of macrolides may have a role in the selection of resistance . Analysis of macrolide prescribing and resistance patterns indicates a correlation between increasing macrolide resistance and the increased use of newer, long-acting macrolides, although further study is required to investigate the causality of this correlation . In order to attempt to prevent the further spread of resistance, antibiotic choice should maximize the opportunity for bacterial eradication. Eur J Pediatr Surg, 1999 Feb, 9(1), 4 - 7 Post-pneumonic thoracic empyema in children: a continued surgical challenge; Gofrit ON et al.; The optimal treatment of post-pneumonic thoracic empyema in children is controversial . In this retrospective study, we review our seven-year experience with open surgical drainage in this condition . Between July 1, 1989, and June 30, 1996, 20 children (median age 2.7 years, range 1-8 years) underwent thoracotomy for post-pneumonic empyema in our department . The diagnosis of thoracic empyema was established by the combination of exudate in a pleural tap and the demonstration of multi-loculated pleural effusion by either chest ultrasound or computerized tomography of the chest . The surgical approach was through a posterolateral mini-thoracotomy under general anesthesia . Intrapleural debris, gelatinous, and fibrinous material were evacuated and drains were placed, under vision, at the most dependent pleural locations . The mean length of pre-hospital illness was 5 days (S.D . 3.1 days) and the mean hospital length of stay in a pediatric ward prior to surgery, during which all children received intravenous antibiotics, was 9.4 days (S.D . 7.7 days) . A causative pathogen was identified in 8 cases: Streptococcus pneumoniae in 6 cases, Streptococcus group A, and H . influenzae each in one case . Cultures from the pus removed during surgery were sterile for all 19 children who received antibiotics for more than 24 hours prior to surgery . Within 48 hours after surgery, fever dropped to < 37.5 degrees C in 85% of the cases . The postoperative course was uneventful in all cases and the children were discharged home 9 days (S.D . 2.8 days) after surgery . We conclude that open mini-thoracotomy and removal of the entire empyema sac is a safe and curative procedure for children with thoracic empyema. Glycobiology, 1999 May, 9(5), 469 - 79 Sequential deglycosylation and utilization of the N-linked, complex-type glycans of human alpha1-acid glycoprotein mediates growth of Streptococcus oralis; Byers HL et al.; Streptococcus oralis is the agent of a large number of infections in immunocompromised patients, but little is known regarding the mechanisms by which this fermentative organism proliferates in vivo . Glycoproteins are widespread within the circulation and host tissues, and could provide a source of fermentable carbohydrate for the growth of those pathogenic organisms with the capacity to release monosaccharides from glycans via the production of specific glycosidases . The ability of acute phase serum alpha1-acid glycoprotein to support growth of S.oralis in vitro has been examined as a model for growth of this organism on N-linked glycoproteins . Growth was accompanied by the production of a range of glycosidases (sialidase, N-acetyl-beta-D-glucosaminidase, and beta-D-galactosidase) as measured using the 4-methylumbelliferone-linked substrates . The residual glycoprotein glycans remaining during growth of this organism were released by treatment with hydrazine and their analysis by HPAEC-PAD and MALDI demonstrated extensive degradation of all glycan chains with only terminal N-acetylglucosamine residues attached to asparagines of the protein backbone remaining when growth was complete . Monosaccharides were released sequentially from the glycans by S.oralis glycosidases in the order sialic acid, galactose, fucose, nonterminal N-acetylglucosamine, and mannose due to the actions of exo-glycosidic activities, including mannosidases which have not previously been reported for S.oralis . All released monosaccharides were metabolized during growth with the exception of fucose which remained free in culture supernatants . Direct release of oligosaccharides was not observed, indicating the absence of endo-glycosidases in S.oralis . We propose that this mechanism of deglycosylation of host glycoproteins and the subsequent utilization of released monosaccharides is important in the survival and persistence of this and other pathogenic bacteria in vivo. Microbiology, 1999 Jan, 145 ( Pt 1), 151 - 7 Structure and transcriptional regulation of the gene encoding pyruvate formate-lyase of a ruminal bacterium, Streptococcus bovis; Asanuma N et al.; The gene (pfl) encoding pyruvate formate-lyase (Pfl) from Streptococcus bovis was sequenced . The deduced amino acid sequence of Pfl was similar to Streptococcus mutans Pfl, and included the conserved regions necessary for free-radical formation and a catalytic site . The Pfl of S . bovis appeared to be a free-radical-containing enzyme because of its dioxygen sensitivity and its amino acid sequence similarity with the Escherichia coli enzyme . The pfl mRNA of S . bovis was approximately 2.3 kb and was transcribed in a monocistronic fashion . When cells were grown in batch culture at pH 6.9, the level of pfl transcript increased as the growth phase changed from exponential growth to stationary phase . This result was in constrast to the previous observation that the level of lactate dehydrogenase (Ldh) mRNA decreased during the later stages of growth . Continuous culture experiments conducted at pH 6.9 under glucose-limited and ammonia-limited conditions revealed that pfl mRNA was decreased by an excess supply of glucose, as well as by a high growth rate . On the contrary, ldh mRNA increased when excess glucose was supplied and the growth rate was high . The amount of pfl mRNA in cells was lower at pH 4.5 than pH 6.9, whereas the level of ldh mRNA was higher at pH 4.5 . This result was consistent with the amounts of Pfl and Ldh in cells and the proportion of formate and lactate produced . These results support the hypothesis that S . bovis regulates Pfl and Ldh synthesis at the transcriptional level in response to growth conditions. Oral Microbiol Immunol, 1999 Feb, 14(1), 21 - 6 Simultaneous induction of specific immunoglobulin A--producing cells in major and minor salivary glands after tonsillar application of antigen in rabbits; Inoue H et al.; The immunoglobulin A (IgA)-producing cells in the stroma of major salivary glands are induced by antigenic stimulation of the mucosal immune system . Whether such cells also are induced in minor salivary glands by this stimulation remains to be determined . After application of sheep red blood cells to the palatine tonsils every 3 days for 6 weeks, anti-sheep red blood cell IgA was detected in saliva both by agglutination tests and by enzyme-linked immunosorbent assay . Using enzyme-linked immunospot assay, an increase in the number of anti-sheep red blood cell IgA-producing cells was found in minor as well as in major salivary glands of the sixth week of application; such cells constituted 4.9% to 5.9% of the total number of IgA-producing cells in these tissues . Tonsillar application of whole cells of formalin-killed Streptococcus sobrinus induced anti-S . sobrinus IgA in saliva . The number of anti-S . sobrinus IgA-producing cells in the above glands simultaneously increased over 6 weeks, and reached 5.2-5.6% of the total number of IgA-producing cells. Can Respir J, 1999 Jan-Feb, 6 Suppl A, 10A - 4A Emergency department management of pneumonia; Talan DA et al.; Many patients with pneumonia, especially those who are more severely ill, have their first medical contact in the emergency department . Pneumonia is usually diagnosed with appropriate signs and symptoms, although these can be lacking in the very young or the old . Gram stain and culture are seldom useful . The choice of appropriate antibiotic is usually determined by degree of illness and microbiological epidemiology . The most important decision made in the emergency department is whether to admit the patient with pneumonia to hospital; this decision can be aided by the use of clinical predictive rules . Initial treatment of pneumonia includes supportive care as needed (oxygen, intubation and bronchodilators) and an empirically chosen antibiotic . Appropriate choices include macrolides and azalides for low risk out-patients, and either a combination cephalosporin and macrolide or an extended spectrum fluoroquinolone in anticipation of drug-resistant Streptococcus pneumoniae for high risk out-patients and in-patients. Mol Microbiol, 1999 Mar, 31(5), 1489 - 98 Induction of an AP endonuclease activity in Streptococcus mutans during growth at low pH; Hahn K et al.; The oral microbe Streptococcus mutans uses adaptive mechanisms to withstand the fluctuating pH levels in its natural environment . The regulation of protein synthesis is part of the mechanism of acid adaptation and tolerance in S . mutans . Here, we demonstrate that the organism's acid-inducible protein repertoire includes an AP endonuclease activity . This abasic site-specific endonuclease activity is present at greater levels in cells grown at low pH than in cells grown at pH 7, and is apparently independent of the RecA protein . Experiments using tetrahydrofuran or alpha-deoxyadenosine-containing substrates indicate that the activity induced at low pH may be similar to the activity of exonuclease III from E . coli . Acid-adapted S . mutans also shows an increased survival rate after exposure to near-UV radiation in both the wild type and a recA strain . Far-UV radiation resistance is observed in the wild type only . The endonuclease activity was purified approximately 500-fold from an S . mutans recA mutant strain grown at pH 5 . Initial characterization revealed a 3' to 5' exonuclease activity, and showed additional functional similarities to DNA repair enzymes from other organisms. J Immunol, 1999 Apr 15, 162(8), 4762 - 72 The origin and function of soluble CD14 in experimental bacterial meningitis; Cauwels A et al.; Murine experimental meningitis models induced by either Escherichia coli LPS, live Streptococcus pneumoniae, or Listeria monocytogenes were used to study the origin and potential function of soluble CD14 (sCD14) in the brain during bacterial meningitis . Whereas intracerebral infection caused only a minor and/or transient increase of sCD14 levels in the serum, dramatically elevated concentrations of sCD14 were detected in the cerebrospinal fluid . Reverse-transcriptase PCR and FACS analysis of the leukocytes invading the subarachnoid compartment revealed an active amplification of CD14 transcription and concomitant surface expression . These findings were confirmed by in situ hybridization and immunohistochemical analysis . In contrast, parenchymal astrocytes and microglial cells were shown not to significantly contribute to the elevated levels of sCD14 . Simultaneous intracerebral inoculation of rsCD14 and S . pneumoniae resulted in a markedly increased local cytokine response . Taken together, these data provide the first evidence that sCD14 can act as an inflammatory co-ligand in vivo . Thus, during bacterial meningitis, sCD14 is massively released by intrathecal leukocytes, and the sCD14 found in the cerebrospinal fluid can play an important role in the pathogenesis of this disease. Neurosurgery, 1999 Apr, 44(4), 864 - 6; discussion 866-8 Infratentorial subdural empyema, pituitary abscess, and septic cavernous sinus thrombophlebitis secondary to paranasal sinusitis: case report; Sahjpaul RL et al.; OBJECTIVE AND IMPORTANCE: Infratentorial empyema, pituitary abscess, and septic cavernous sinus thrombophlebitis are all rare and potentially lethal conditions . The occurrence of all three in a single patient has not previously been described . We present such a case occurring in a young, otherwise healthy man . CLINICAL PRESENTATION: A 26-year-old man with a remote history of sinusitis developed rapidly progressive headache, fever, right eye pain, swelling, proptosis, and visual impairment . Magnetic resonance imaging demonstrated diffuse pansinusitis, including sphenoid sinusitis, and extension of inflammation and infection into the adjacent cavernous sinuses, pituitary gland, and posterior fossa . INTERVENTION: Urgent drainage of the ethmoid and maxillary sinuses was performed; pus was not identified . The patient continued to deteriorate clinically with worsening of visual acuity . Computed tomography of the head performed the next day revealed worsening hydrocephalus and an enlarging posterior fossa subdural empyema . Urgent ventricular drainage and evacuation of the empyema was performed, and subsequently, the patient's clinical course improved . The microbiology results revealed alpha hemolytic streptococcus and coagulase-negative staphylococcus species . The patient survived but during the follow-up period had a blind right eye and pituitary insufficiency . CONCLUSION: Paranasal sinusitis can have devastating intracranial sequelae . Involvement of the adjacent pituitary gland and cavernous sinuses can result in serious neurological morbidity or mortality, and retrograde spread of infection through the basal venous system can result in subdural or parenchymal brain involvement . A high index of suspicion and aggressive medical and surgical treatment are crucial for patient survival, but the morbidity rate remains high . Our patient survived but lost anterior pituitary function and vision in his right eye. Mol Microbiol, 1999 Mar, 31(5), 1463 - 75 Expression of different group A streptococcal M proteins in an isogenic background demonstrates diversity in adherence to and invasion of eukaryotic cells; Berkower C et al.; The M protein of group A streptococcus (GAS) is considered to be a major virulence factor because it renders GAS resistant to phagocytosis and allows bacterial growth in human blood . There are more than 80 known serotypes of M proteins, and protective opsonic antibodies produced during disease in humans are serotype specific . M proteins also mediate bacterial adherence to epithelial cells of skin and pharynx . GAS strains vary in the genomic organization of the mga regulon, which contains the genes encoding M and M-like proteins and other virulence factors . This diversity of organization makes it difficult to assess virulence of M proteins of different serotypes, unless they can be expressed in an isogenic background . Here, we express M proteins of different serotypes in the M protein- and protein F1-deficient GAS strain, SAM2, which also lacks M-like proteins . Genes encoding M proteins of different serotypes (emmXs) have been integrated into the SAM2 chromosome in frame with the emm6.1 promoter and its mga regulon, resulting in similar levels of emmX expression . Although SAM2 exhibits a very low level of adherence to and invasion of HEp-2 and HaCaT cells, a SAM2-derived strain expressing M6 protein adheres to and invades both cell types . In contrast, the isogenic strain expressing M18 protein adheres to both cell types, but invades with a very low efficiency . A strain expressing M3 protein adheres to both types of cells, but its invasion of HEp-2 cells is serum dependent . A GAS strain expressing M6 protein does not compete with the isogenic strain expressing M18 protein for adherence to or invasion of HaCaT cells . We conclude that M proteins of different serotypes recognize different repertoires of receptors on the surfaces of eukaryotic cells. Biochemistry, 1999 Apr 13, 38(15), 4691 - 700 Characteristics and crystal structure of bacterial inosine-5'-monophosphate dehydrogenase; Zhang R et al.; IMP dehydrogenase (IMPDH) is an essential enzyme that catalyzes the first step unique to GTP synthesis . To provide a basis for the evaluation of IMPDH inhibitors as antimicrobial agents, we have expressed and characterized IMPDH from the pathogenic bacterium Streptococcus pyogenes . Our results show that the biochemical and kinetic characteristics of S . pyogenes IMPDH are similar to other bacterial IMPDH enzymes . However, the lack of sensitivity to mycophenolic acid and the Km for NAD (1180 microM) exemplify some of the differences between the bacterial and mammalian IMPDH enzymes, making it an attractive target for antimicrobial agents . To evaluate the basis for these differences, we determined the crystal structure of the bacterial enzyme at 1.9 A with substrate bound in the catalytic site . The structure was determined using selenomethionine-substituted protein and multiwavelength anomalous (MAD) analysis of data obtained with synchrotron radiation from the undulator beamline (19ID) of the Structural Biology Center at Argonne's Advanced Photon Source . S . pyogenes IMPDH is a tetramer with its four subunits related by a crystallographic 4-fold axis . The protein is composed of two domains: a TIM barrel domain that embodies the catalytic framework and a cystathione beta-synthase (CBS) dimer domain of so far unknown function . Using information provided by sequence alignments and the crystal structure, we prepared several site-specific mutants to examine the role of various active site regions in catalysis . These variants implicate the active site flap as an essential catalytic element and indicate there are significant differences in the catalytic environment of bacterial and mammalian IMPDH enzymes . Comparison of the structure of bacterial IMPDH with the known partial structures from eukaryotic organisms will provide an explanation of their distinct properties and contribute to the design of specific bacterial IMPDH inhibitors. Z Rheumatol, 1999 Feb, 58(1), 31 - 4 {Pneumococcal septicemia in functional asplenia: first manifestation of systemic autoimmune disease?}; Germing U et al.; A 35 year old female was admitted into the hospital because of rapid onset fever and chills . Streptococcus pneumoniae could be isolated from blood as the responsible pathogen for septicemia . Necroses of fingers and feet occurred . The clinical signs of an overwhelming post-splenectomy infection (OPSI) were evident . High-dose penicillin was administered and the patient recovered . Howell-Jolly-bodies were seen in peripheral blood smears . A spleen within normal size could be demonstrated in CT and sonography . Angiologic findings showed intact splenic arteries and a normal vein, whereas the small splenic vessels were rare . MRT of the spleen using Endorem (Fe), showed only a minimal uptake of the RES . In a scintigram of spleen and liver using 320 MBq Tc-99m nanokoll, the spleen was not visible . Thus, functional asplenia was demonstrated by Howell-Jolly-Bodies and by image methods . An increased antinuclear antibody level and a Sm-antibody lead to the diagnosis of undifferentiated connective tissue disease . As far as we know this is the first case that functional asplenia was the first symptom of a systemic autoimmune disease. J Bacteriol, 1999 Apr, 181(8), 2652 - 4 The type 2 capsule locus of Streptococcus pneumoniae; Iannelli F et al.; The type 2 capsule locus of Streptococcus pneumoniae was characterized in Avery's strain D39, which is the parent strain of the standard transformation recipients currently used in pneumococcal research and is largely used as a virulent strain in studies on the pathogenesis of pneumococcal infections . The capsule locus was sequenced by using a 21.7-kb PCR fragment from the D39 genome as a template . Sequence data analysis showed the presence of 18 open reading frames, 17 of which have the same direction of transcription and all of which are potentially involved in capsule biosynthesis . It was also shown that R36A and R6, which are unencapsulated (rough) derivatives of D39, carry a 7,504-bp deletion involving nine capsule genes. Semin Respir Infect, 1999 Mar, 14(1), 18 - 30 Pleural space infections: microbiology and antimicrobial therapy; Everts RJ et al.; Although most recognized pleural space infections are caused by Staphylococcus aureus, Streptococcus pneumoniae, enteric gram-negative bacilli, or anaerobic bacteria, the spectrum of possible pathogens is broad and includes fungi and even protozoa, reflecting the mixed origins of these infections . When pleural space infection is suspected, a diagnostic thoracocentesis is indicated . An immediate gram-stained smear of directly aspirated pleural fluid often can guide the physician's initial treatment . After recovery of the pathogens, optimal antibiotic therapy should be based on standardized susceptibility testing and consensus guidelines . Antibiotic therapy alone may be curative, but adequate drainage must also be achieved in most cases. Pediatr Dent, 1999 Mar-Apr, 21(2), 91 - 6 Prevalence of caries in urban Australian aborigines aged 1-3.5 years; Seow WK et al.; PURPOSE: This study investigated the prevalence and etiological factors associated with caries in a group of young Australian aboriginal children from 1 to 3.5 years of age . METHODS: One hundred and forty-seven healthy infants, aged from 1 to 3.5 years, attending a community health center in Brisbane, a nonfluoridated state capital city, were randomly selected for the study . RESULTS: The caries prevalence was 39% by subjects and 32% by the total number of teeth present . The mean number of decayed, filled teeth (dtf) was 2.5 +/- 0.4, which is more than twice the figure for 3-year-old children in Australia . Furthermore, the filled (f) component represented only 1% of the total dft, suggesting very low treatment levels . Increased caries experience of the infants was strongly associated with high dental plaque scores, high levels of Streptococcus mutans infection, and sleep-time consumption of milk containing added sugar . CONCLUSION: The results suggest that urban Australian aboriginal infants are at high risk for caries, and that preventive strategies are urgently required. Curr Pharm Des, 1998 Apr, 4(2), 119 - 32 Recent developments in tetracycline antibiotics; Sum PE et al.; The rapid emergence of pathogenic bacteria resistant to tetracyclines and other currently available antibiotics has caused serious concern among medical professionals . It has heightened resurgent interest in studying the mechanisms of resistance and in developing new antibiotics . A comprehensive review has outlined the developments of tetracyclines prior to 1980 {47} . This review will highlight the pertinent advances in the tetracycline field during the last two decades, including recent progress on elucidating the mechanisms of resistance, and the development of novel tetracyclines to combat bacterial resistance . Most of the new tetracycline derivatives described in this review have been either prepared semisynthetically or isolated from fermentation . In the semisynthetic area, efflux inhibitors that are effective in an in vitro model have been identified . A new class of tetracyclines, named glycylcyclines has been the subject of numerous reports, and will be the major focus of this review . The glycylcyclines are currently the only derivatives that exhibit antibacterial activity comparable to that of the early tetracyclines when they were first introduced . These compounds show potent activity against a broad spectrum of Gram-positive and Gram-negative bacteria, including strains that carry the two major tetracycline-resistance determinants, efflux and ribosomal protection . Two of the glycylcycline derivatives . DMG-MINO and DMG-DMDOT, have been studied by several groups of investigators against a large number of clinical pathogens isolated from various sources . The spectrum of activity of these compounds includes organisms with resistance to antibiotics other than tetracyclines, e.g., methicillin-resistant staphylococci, penicillin-resistant streptococcus pneumoniae, and vancomycin-resistant enterococci . Their in vitro, as well as in vivo activity against bacteria with characterized tetracycline- or minocycline-resistant elements will be summarized . The structure-activity relationships of glycylcyclines and their mode of action will also be discussed. J Endod, 1999 Jan, 25(1), 34 - 7 Growth inhibition of Streptococcus anginosus (milleri) by three calcium hydroxide sealers and one zinc oxide-eugenol sealer; Mickel AK et al.; The inhibition of growth of Streptococcus anginosus (milleri) by three calcium hydroxide sealers--calciobiotic root canal sealer (Hygienic Corporation, Akron, OH), Sealapex (Kerr Division, Sybron Corporation, Romulus, MI), and Apexit (Vivadent, USA, Amherst, NY)--was compared with a zinc oxide-eugenol sealer: Roth (Roth International, Chicago, IL) . Sixteen brain heart infusion agar plates were inoculated with S . anginosus . Each plate was divided into five separate areas . In each area, a 0.1 ml droplet of a given sealer was placed such that each plate had five areas with the same sealer . There were four plates (for each of the four sealers) for a total of 20 observation areas to evaluate each sealer . The plates were incubated at 37 degrees C in a 5% CO2 atmosphere . After varying periods of incubation, the zones of inhibition of bacterial growth were observed and measured . Roth sealer had a statistically significant larger mean zone of inhibition than the calcium hydroxide sealers . However, all of the sealers exhibited clinically relevant antimicrobial activity . It is likely that the eugenol in the Roth sealer is responsible for its greater antimicrobial activity. AIDS Res Hum Retroviruses, 1999 Mar 20, 15(5), 451 - 9 Antigenicity and immunogenicity of the V3 domain of HIV type 1 glycoprotein 120 expressed on the surface of Streptococcus gordonii; Oggioni MR et al.; Five different V3 domains of HIV-1 gp120 were expressed on the surface of the gram-positive bacterium Streptococcus gordonii, a model live vector for vaccine delivery . Sera of HIV-1-infected individuals and human monoclonal antibodies specifically recognized the gp120 sequences on the bacterial surface . Recombinant V3 from the reference HIV-1 strain MN was also shown to retain a conformation that allowed reaction with a conformation-specific monoclonal antibody . A V3-specific serum antibody response was detected in mice immunized both by subcutaneous injection and by vaginal colonization . V3-specific IgG2a antibodies, suggestive of a Th1 response, were found in the sera of mice colonized by recombinant bacteria. Vet Immunol Immunopathol, 1999 Feb 22, 67(3), 235 - 46 Streptococcus equi but not Streptococcus zooepidemicus produces potent mitogenic responses from equine peripheral blood mononuclear cells; Anzai T et al.; Streptococcus equi causes equine strangles . The acute disease has many of the hallmarks of an acute response including high fever, elevated plasma fibrinogen and neutrophilia, affects known to be mediated by proinflammatory cytokines . The objective of this study was to screen-culture supernatants from equine clinical isolates of S . equi and S . zooepidemicus for stimulation of mitogenic responses by horse peripheral blood mononuclear cells . Mitogenicity comparable to that of concanavalin A was detected in culture supernatants of S . equi strains but not in those of S . zooepidemicus . Mitogenicity was neutralised by Proteinase K and a post-strangles convalescent serum, and evidence for the presence of both thermo-resistant and thermo-labile mitogenic factors was obtained . Release of proteinaceous immunogenic mitogens in combination with the antiphagocytic protein SeM unique to S . equi may therefore contribute to some of the severe clinical manifestations of acute strangles in the horse. Arch Dis Child Fetal Neonatal Ed, 1998 Nov, 79(3), F202 - 5 Placental antibody transfer: influence of maternal HIV infection and placental malaria; de Moraes-Pinto MI et al.; AIM: To determine the influence of placental malaria, maternal HIV infection, and maternal hypergammaglobulinaemia on transplacental IgG antibody transfer . METHODS: One hundred and eighty materno-neonatal pairs from a Malawian population were assessed . Cord and maternal serum samples were tested for total serum IgG antibody titres using nephelometry, and for specific IgG antibody titres to Streptococcus pneumoniae, measles, and tetanus toxoid antibodies using an enzyme linked immunosorbent assay (ELISA) . RESULTS: Multiple regression analyses showed that placental malaria was associated with a decrease in placental IgG antibody transfer to S pneumoniae and measles to 82% and 81%, respectively . Maternal HIV infection was associated with a reduction in IgG antibody transfer to S pneumoniae to 79%; raised maternal total serum IgG titres were correlated with S pneumoniae and measles IgG antibody transfer reduction to 86% and 87%, respectively . No effect was seen with tetanus toxoid antibody transfer . CONCLUSION: The combined influence of placental malaria, maternal HIV infection, and maternal hypergammaglobulinaemia seems to be linked to the low transplacental antibody transfer observed in the Malawian population. Intensive Care Med, 1999 Feb, 25(2), 198 - 206 Epidemiological features and prognosis of severe community-acquired pneumococcal pneumonia; Georges H et al.; OBJECTIVE: To describe risk factors of severe pneumococcal community-acquired pneumonia and to study variables influencing outcome . DESIGN: Retrospective (1987-1992) and prospective (1993-1995) study . SETTING: Three participating ICUs from primary care hospitals . PATIENTS: Five hundred and five patients (mean age: 63 +/- 17 years) with severe community-acquired pneumonia (CAP) . Three groups of patients were defined: pneumococcal CAP (group 1), CAP with microbial diagnosis other than Streptococcus pneumoniae (group 2), CAP from group 2 and CAP without microbial diagnosis (group 3) . MEASUREMENTS AND RESULTS: Admission data and data on the disease's course were recorded . The mean Simplified Acute Physiologic Score (SAPS) was 12.5 +/- 5.4 . On admission 288 (57 %) patients were mechanically ventilated (mv) and 82 (16.2 %) required inotropic support . A microbial diagnosis was established for 309 (61.2%) patients . S . pneumoniae was isolated in 137 (27.1%) patients . Severe pneumococcal CAP was independently associated with male sex (p = 0.01), lack of antibiotics use before admission (p = 0.0001), non-aspiration pneumonia (p = 0.01) and septic shock (p = 0.0001) . The overall mortality rate was 27.5 % (29.2 % in group 1) . In patients with severe pneumococcal CAP, multivariate analysis showed that leukopenia less than 3,500/mm3 (p = 0.0004), age over 65 years (p = 0.01), septic shock (p = 0.01), sepsis related complications (p = 0.0001), ICU complications (p = 0.001) and inadequacy of antimicrobial therapy (p = 0.002) worsened the prognosis . CONCLUSIONS: Few features facilitate the identification of pneumococcal CAP on ICU admission . The prognosis is mostly related to severity of illness (leukopenia, septic shock) while comorbidities do not seem to influence outcome . Sepsis-related disorders, ICU complications and adequate antimicrobial chemotherapy are the major variables affecting the outcome during an ICU stay. Planta Med, 1999 Mar, 65(2), 178 - 9 Composition and antimicrobial activity of the essential oil of Peumus boldus leaves; Vila R et al.; The composition and the antimicrobial activity of the essential oil from the leaves of Peumus boldus is investigated . Analyses of the oil obtained by hydrodistillation were carried out by GC and GC-MS using columns of two different stationary phases . Fractionation of the essential oil by column chromatography on silica gel was performed to improve identification of some constituents . More than 90% of the total oil (46 components) was identified, major constituents being monoterpenes (90.5%), among which limonene (17.0%), p-cymene (13.6%), 1.8-cineole (11.8%), and beta-phellandrene (8.4%) reached the highest percentages . Determination of the minimal bactericidal or fungicidal concentration against several microorganisms showed interesting activities towards Streptococcus pyogenes, Micrococcus sp., and Candida sp. Biomed Chromatogr, 1999 Feb, 13(1), 46 - 50 GC-MS analysis of diaminopimelic acid stereoisomers and amino acid enantiomers in rumen bacteria; Schieber A et al.; The amounts and the configuration of the stereoisomers of 2,6-diaminopimelic acid (Dap) and the enantiomeric content of other amino acids were determined in five individual species (Fibrobacter succinogenes, Streptococcus bovis, Selenomonas ruminantium, Prevotella ruminicola and Anaerovibrio lipolytica) of rumen bacteria, and in samples of mixed rumen bacteria isolated from sheep . The separation and quantification of the Dap stereoisomers was achieved by gas chromatography (GC) of trifluoroacetyl 2-propyl esters on a Chirasil-L-Val fused silica column, and detection was achieved by selected ion monitoring mass spectrometry (SIM-MS) . No isomers of Dap were detected in S . bovis and P . ruminicola, two of the bacterial isolates . LL- and DD-Dap were not detected in any of the bacterial samples . As only the meso-isomer of Dap was detected in these microorganisms, it was quantified by adding LL-Dap as an internal standard before the bacteria were acid-hydrolyzed . Amounts of between 4.8 and 12.0 mg meso-Dap per gram of bacterial dry matter (DM) were determined . The presence in the rumen bacteria of free amino acid enantiomers, extractable with 70% aqueous ethanol, were determined by GC-SIM-MS; the D-amino acids were predominantly Ala, Asp and Glu, but there was considerable variation between the species. J Infect Dis, 1999 May, 179(5), 1293 - 6 Type-specific opsonophagocytosis of group A Streptococcus by use of a rapid chemiluminescence assay; Villasenor-S A et al.; A whole-blood chemiluminescence (CL) assay was developed to determine the presence of type-specific opsonic antibodies against group A streptococcus (GAS) . Convalescent sera with high bactericidal activities against an M-1 serotype were used to opsonize different M-types of GAS . CL responses were monitored for 20 min, and results were expressed as integral counts/minute per phagocyte . CL responses of phagocytes incubated with M-1 GAS opsonized with homologous (M-1) serum were significantly higher than responses of phagocytes incubated with heterologous (M-3) GAS . Adsorption of convalescent serum against the homologous, but not the heterologous, strain markedly reduced the CL response, demonstrating type specificity . The CL assay showed a high correlation with the indirect bactericidal test (r=0.90) . In conclusion, this CL assay is a rapid, highly sensitive, specific, and reproducible method for quantifying type-specific opsonic antibodies against GAS and will be a useful tool for future clinical, basic science, and epidemiological studies. Minerva Pediatr, 1998 Sep, 50(9), 395 - 7 {Sepsis caused by Streptococcus pneumonia in newborn infants . 2 case reports}; Pugliese A et al.; Streptococcus pneumoniae is responsible for 2% of all neonatal sepsis . The results of epidemiological studies suggest that newborns acquire infection by the ascending route or during the passage through the birth canal . It has been hypothesized that colonization of the maternal genital tract with S . pneumoniae might be caused by contamination of obstetric instruments with the microorganism or by sexual practices, particularly oro-genital contact . From our NICU's database, two cases of newborn sepsis due to Streptococcus pneumoniae, occurred between 1988 and 1996 have been found; the first case presented a fatal disseminated intravascular coagulation (DIC), the second a severe respiratory failure . Antibiotic treatment of women carrying S . pneumoniae in the genital tract and their infants should be strongly recommended, on the basis of the potentially serious consequences for the infants. Bull World Health Organ, 1998, 76(6), 641 - 50 Antibiotic resistance of nasopharyngeal isolates of Streptococcus pneumoniae from children in Lesotho; Mthwalo M et al.; Villages associated with the Lesotho Highlands Development Agency were randomized with a bias in favour of larger villages, and children < 5 years of age from cluster-randomized households in these villages were chosen for the assessment of antibiotic resistance in pneumococci . Children of the same age group attending clinics in the capital, Maseru, were selected for comparison . Nasopharyngeal cultures of Streptococcus pneumoniae from both groups of children were examined for antibiotic resistance and a questionnaire was used to assess risk factors for the acquisition of resistant strains . Carriage of penicillin- and tetracycline-resistant pneumococci was significantly higher among 196 Maseru children compared with 324 rural children (P < 0.05 and P = 0.01, respectively) . Maseru children tended to visit clinics at an earlier age compared with their rural counterparts . The rural children were less exposed to antibiotics (P < 0.01), were less frequently hospitalized (P < 0.001), and rarely attended day care centres (P < 0.001) . The very low incidence of antibiotic resistance in rural Lesotho and the higher incidence in Maseru are in stark contrast with the much higher frequencies found in the Republic of South Africa, many European countries, and the USA. Pediatr Dev Pathol, 1999 May-Jun, 2(3), 215 - 20 Hepatic subcapsular hematomas in fetuses and neonatal infants; Singer DB et al.; In fetuses and neonates hepatic subcapsular hematomas are relatively common lesions and may be life-threatening . Conditions previously associated with these hematomas include trauma, coagulopathies, hypoxia, sepsis, pneumothorax, maternal diseases, and placental lesions . In this study of 755 perinatal autopsies, hepatic subcapsular hematomas were found in 52 (6.9%) cases, including 31 stillborn fetuses and 21 liveborn infants . The average body weight was 690 g . A comparison group consisted of 52 temporally proximal autopsies of fetuses and neonates without hematomas . Body weights, gender, maternal age, and stillbirth or postnatal survival were matched as closely as possible while evaluating the presence or absence of sepsis, pneumothorax, cerebral germinal matrix hemorrhage, trauma, coagulopathy, placental lesions, and maternal diseases . Sepsis was associated with 62% of the cases with hepatic subcapsular hematomas and with 25% of the comparison group (P =.0001) . Group B streptococcus infection was the most common cause of sepsis, but many different organisms were isolated . Cerebral germinal matrix hemorrhages were present in 35% of the cases with hematomas and in 14% of the comparison group (P =.0001) . No other lesions or conditions were statistically different in the study group versus the comparison group . The delicacy of the hepatic capsule and its connections to the collagen along the sinusoids provide insight for the pathogenesis of hematomas in premature fetuses and neonates . We conclude that sepsis is present in most perinatal cases of hepatic subcapsular hematomas and that such patients also frequently have cerebral germinal matrix hemorrhages . Each of these lesions is a greater hazard among very small premature fetuses or neonates than among older fetuses and neonates. Am Surg, 1999 Apr, 65(4), 307 - 10 Factors affecting the surgical management of infective endocarditis; Cassada DC et al.; Congestive heart failure and septic embolism complicate the clinical course of patients with infective endocarditis (IE) . This study reviews the clinical records of patients with systemic disease secondary to IE and stratifies their disease severity according to individual risk factors and medical, and surgical interventions . The hospital records of all patients presenting to our institution from 1992 through 1997 with heart valve destruction secondary to IE were reviewed . Ten patients with hemodynamically significant valve lesions were included in this study: seven with aortic valve disease and two with mitral valve disease, and one with combined aortic and mitral valve lesions . All were diagnosed by echocardiogram . All ten patients experienced systemic septic arterial emboli: four intracranial lesions, four visceral lesions, and three extremity arterial occlusive events . Two patients required peripheral arterial repair . Cultures revealed infection secondary to Staphylococcus aureus in five, Streptococcus species in three, Coxiella species in one, and an unidentified organism in one patient . Seven patients underwent valve replacement . Three patients died from their disease processes . Statistical significance was established by Wilcoxon rank analysis with a two-tailed P < 0.05 . Patients with IE secondary to staphylococcal infections suffered a more acute and virulent disease process (P = 0.04), with a 40 per cent mortality rate in the first 48 hours . There was no increased incidence of embolization associated with longer duration of symptoms (P = 0.32) . Surgical repair conferred improved clinical outcome as compared with no surgical intervention (P = 0.03) . Improved patient outcome was associated with nonstaphylococcal infection (P = 0.02), and a successful initial antibiotic regimen (P = 0.03) . Peripheral arterial repair was successful in both cases. Korean J Ophthalmol, 1998 Dec, 12(2), 108 - 11 Streptococcal keratitis after myopic laser in situ keratomileusis; Kim HM et al.; A 24-year-old healthy male underwent uncomplicated laser in situ keratomileusis (LASIK) in left eye . One day after the surgery, he complained of ocular pain and multiple corneal stromal infiltrates had developed in left eye . Immediately, the corneal interface and stromal bed were cleared, and maximal antibiotic treatments with fortified tobramycin (1.2%) and cefazolin (5%) were given topically . The causative organism was identified as 'Streptococcus viridans' both on smear and culture . Two days after antibiotic therapy was initiated, the ocular inflammation and corneal infiltrates had regressed and ocular pain was relieved . One month later, the patient's best corrected visual acuity had returned to 20/20 with -0.75 -1.00 x 10 degrees, however minimal stromal scarring still remained . This case demonstrates that microbial keratitis after LASIK, if treated promptly, does not lead to a permanent reduction in visual acuity. FEMS Microbiol Lett, 1999 Mar 15, 172(2), 131 - 5 Transformation of a type 4 encapsulated strain of Streptococcus pneumoniae; Bricker AL et al.; Streptococcus pneumoniae strain JNR.7/87 is a highly virulent, type 4 encapsulated Gram-positive bacterium whose transformability has not been tested previously, and whose genome is currently being sequenced . The strain was transformed at very low efficiency by addition of exogenous competence-stimulating peptide: However, the efficiency was too low and irreproducible to be useful in many genetic studies . Therefore, the effects on transformation efficiency of changing different components of competence-stimulating peptide-induced transformation have been examined . Screening of growth media was followed by optimization of pre-induction culture acidification, glycine concentration, and induction time . An optimized protocol was developed whereby S . pneumoniae strain JNR.7/87 was transformed reproducibly with a streptomycin resistance (SmR) marker at an efficiency of approximately 10(5) colony forming units per 10(8) cells. Antimicrob Agents Chemother, 1999 Apr, 43(4), 876 - 81 Pharmacodynamics of vancomycin for the treatment of experimental penicillin- and cephalosporin-resistant pneumococcal meningitis; Ahmed A et al.; With the emergence of beta-lactam antibiotic resistance among strains of Streptococcus pneumoniae, vancomycin has assumed an important role in the treatment of bacterial meningitis . Using the rabbit meningitis model, we evaluated the pharmacokinetics and pharmacodynamics of vancomycin in this setting . Animals were given 80 mg/kg of body weight daily in two or four divided doses to determine the penetration and activity of vancomycin in cerebrospinal fluid (CSF); each regimen was administered with and without dexamethasone . Mean peak (2 h) concentrations in CSF that were four- to eightfold higher than the minimum bactericidal concentration (MBC; 0.5 microgram/ml) for the pathogen were adequate for bacterial clearance . In both groups concentrations in CSF remained higher than the MBC for greater than 80% of the respective dosing intervals, and the penetration of vancomycin into CSF was 20% . Mean concentrations in CSF at 24 to 36 h of therapy were lower than those achieved during the first 12 h, consistent with a decline in the level of antibiotic entry into CSF as inflammation wanes . Rates of bacterial clearance were similar for the two regimens, and for all animals cultures of CSF were sterile by 36 h . The coadministration of dexamethasone significantly reduced the penetration of vancomycin into CSF by 29% and significantly lowered the rate of bacterial clearance during the first 6 h in animals receiving 20-mg/kg doses of vancomycin . For animals receiving 40-mg/kg doses, therapeutic peak concentrations in CSF were obtained even with steroid use, suggesting that the effect of steroids may be circumvented by the use of larger daily doses of vancomycin. Pediatrics, 1999 Apr, 103(4 Pt 1), 783 - 90 A case-control study of necrotizing fasciitis during primary varicella; Zerr DM et al.; OBJECTIVE: An increase in the incidence of necrotizing fasciitis (NF) occurring in previously healthy children with primary varicella was noted in the Washington State area between December 1993 and June 1995 . Our objective was to investigate ibuprofen use and other risk factors for NF in the setting of primary varicella . METHODS: Case-control study . Demographic information, clinical parameters, and potential risk factors for NF were compared for cases and controls . Cases of NF were analyzed to identify potential determinants of NF complicated by renal insufficiency and/or streptococcal toxic shock syndrome . Multivariate logistic regression was used to evaluate the association between ibuprofen use and NF . A case was defined as a child with NF hospitalized within 3 weeks of primary varicella (n = 19) . Controls were children hospitalized with a soft tissue infection other than NF within 3 weeks of primary varicella (n = 29) . Odds ratios (ORs) of ibuprofen, as well as other potential risk factors were evaluated . In addition, demographic and clinical data as well as other potential risk factors were compared between cases and controls . RESULTS: After controlling for gender, age, and group A streptococcus isolation, cases were more likely than controls to have used ibuprofen before hospitalization (OR, 11 . 5; 95% confidence interval, 1.4 to 96.9) . In most children, ibuprofen was initiated after the onset of symptoms of secondary infection . Children with NF complicated by renal insufficiency and/or streptococcal toxic shock syndrome were more likely than children with uncomplicated NF to have used ibuprofen (OR, 16.0; 95% confidence interval, 1.0 to 825.0) . Children with complicated NF also had a higher mean maximum temperature (40.9 degrees C vs 39.3 degrees C), and a longer mean duration of secondary symptoms (1.7 days vs 0.6 days) before admission than children with uncomplicated NF . CONCLUSION: Ibuprofen use was associated with NF in the setting of primary varicella . Additional studies are needed to establish whether ibuprofen use has a causal role in the development of NF and its complications during varicella. Antimicrob Agents Chemother, 1999 Apr, 43(4), 988 - 9 Inhibition of the emergence of ciprofloxacin resistance in Streptococcus pneumoniae by the multidrug efflux inhibitor reserpine; Markham PN; Recent evidence supports the contribution of a multidrug efflux mechanism to fluoroquinolone resistance in Streptococcus pneumoniae . In this paper I show that reserpine, an inhibitor of multidrug transporters in gram-positive bacteria, dramatically suppresses the in vitro emergence of ciprofloxacin-resistant variants of S . pneumoniae, suggesting that the combination of a fluoroquinolone with an inhibitor of multidrug transport may help preserve the efficacy of this class of antibiotics. Antimicrob Agents Chemother, 1999 Apr, 43(4), 944 - 6 Presence of mefA and mefE genes in Streptococcus agalactiae; Arpin C et al.; Eighteen unrelated clinical isolates of Streptococcus agalactiae with the M phenotype harbored an mef gene . DNA sequencing showed that one of nine strains contained mefA (producing one amino acid substitution), whereas the remaining eight carried mefE (identity, 100%) . Restriction analysis of PCR products indicated that the nine other strains also contained mefE. Scand J Immunol, 1999 Mar, 49(3), 237 - 43 Kinetics of cytokine release and expression of lymphocyte cell-surface activation markers after in vitro stimulation of human peripheral blood mononuclear cells with Streptococcus pneumoniae; Arva E et al.; The aim of this study was to describe the kinetics of the cytokine release and the expression of activation markers on lymphocytes after stimulation of peripheral blood mononuclear cells (PBMC) with whole killed Streptococcus pneumoniae . The cytokine release and the expression of CD25 and HLA-DR on T cells, and CD69 on T cells, B cells and NK cells, were measured at different times . Our results show that tumour necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-10 and IL-12 reached maximal levels at 24 h, while IL-6, IL-8, TNF-beta and interferon (IFN)-gamma increased throughout the 1-week test period . The strains tested gave an increased expression of CD69 on all cell types, as well as an increase of CD25 and HLA-DR expression on T cells . The maximal CD69 expression was seen after 24 h on T cells and NK cells, while the B-cell expression of CD69 reached a plateau at the same time . All the cells still expressed CD69 on their surfaces after 1 week . In conclusion the results indicate that there was probably an early activation of monocytes leading to a polyclonal activation of lymphocytes. FEBS Lett, 1999 Mar 12, 446(2-3), 299 - 304 Surface display of functional fibronectin-binding domains on Staphylococcus carnosus; Liljeqvist S et al.; The surface expression in Staphylococcus carnosus of three different fibronectin binding domains (FNBDs), derived from fibronectin binding proteins of Streptococcus dysgalactiae and Staphylococcus aureus, has been investigated . Surface localization of the chimeric proteins containing the FNBDs was demonstrated . All three surface-displayed FNBDs were demonstrated to bind fibronectin in whole-cell enzyme-linked binding assays . Furthermore, for one of the constructs, intranasal immunizations with the recombinant bacteria resulted in improved antibody responses to a model immunogen present within the chimeric surface proteins . The implications of the results for the design of live bacterial vaccine delivery systems are discussed. Aust N Z J Obstet Gynaecol, 1999 Feb, 39(1), 108 - 10 Group B streptococcus infection, not birth asphyxia; Keogh JM et al.; This case illustrates 2 main points . Firstly, fetal infection can mimic exactly both the immediate and delayed signs of perinatal asphyxia . Secondly, the placenta may hold the key to the diagnosis of sepsis which may be made difficult in the neonate by labour ward practices such as the use of intrapartum and immediate newborn antibiotics . We strongly support the recommendation that newborn blood and fetal membrane cultures should always be obtained in babies with a diagnosis of 'intrapartum asphyxia and fetal distress' (1) . To this we would add the recommendation that placental histology be performed in these circumstances. Epidemiol Infect, 1999 Feb, 122(1), 77 - 82 Epidemiology of Streptococcus pneumoniae infection in Malaysia; Rohani MY et al.; During a 1-year period from October 1995 to September 1996, 273 isolations of Streptococcus pneumoniae were made from various types of clinical specimens . The majority of the isolates (39.2%) were from sputum whilst 27.5% were from blood, CSF and other body fluids . The organism was isolated from patients of all age groups, 31.1% from children aged 10 years and below, 64.7% of which come from children aged 2 years or below . The majority of the isolates belong to serotypes 1, 6B, 19B, 19F and 23F . Serotypes 1 and 19B were the most common serotypes associated with invasive infection . About 71.9% of the invasive infections were due to serotypes included in the available 23 valent polysaccharide vaccine . The rates of resistance to penicillin and erythromycin were 7.0 and 1.1% respectively . Our findings show that the serotypes of S . pneumoniae causing most invasive infections in Malaysia are similar to those in other parts of the world and the available vaccine may have a useful role in this population. Yonsei Med J, 1998 Dec, 39(6), 546 - 53 Emergence and spread of antimicrobial resistance of Streptococcus pneumoniae in Korea; Song JH; Pneumococcal resistance has become a global issue during the past three decades . One of the major foci of pneumococcal resistance worldwide is the Asian region including Korea, Japan, and Hong Kong . Korea had not been recognized as a focus of pneumococcal resistance until 1995, when serial reports documented the alarmingly high prevalence of penicillin resistance among clinical isolates . Serial reports on penicillin resistance among pneumococcal isolates in Korea ranged from 68% to 77% as of 1995 . Multidrug resistance was also noted in 34% of Korean isolates . Penicillin-binding protein profile analysis, pulsed-field gel electrophoresis, ribotyping, and fingerprinting analysis of pbp genes showed that antibiotic-resistant pneumococci isolated in Korea were genetically related . Data documented the extensive spread of a resistant clone within Korea and between different countries . Besides the injudicious use of antimicrobial agents or the high prevalence of serotypes 23 and 19, the spread of a resistant clone may play an important role in the rapid increase of penicillin resistance in Korea. Yonsei Med J, 1998 Dec, 39(6), 541 - 5 A mutation in QRDR in the ParC subunit of topoisomerase IV was responsible for fluoroquinolone resistance in clinical isolates of Streptococcus pneumoniae; Choi H et al.; Forty-one strains of Streptococcus pneumoniae were isolated at Seoul National University Children's Hospital from 1991 to 1997 . Isolates were divided into six groups based on MI