In vitro activity of fosfomycin against Haemophilus influenzae,Streptococcus pneumoniae and Neisseria species

Summary The minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) of fosfomycin were determined by an agar dilution technique for 100 strains each ofHaemophilus influenzae andStreptococcus pneumoniae, and for 40 strains ofNeisseria species andBranhamella catarrhalis. The median MIC ofH. influenzae was 0.13 mg/l (range 0.008–64 mg/l), ofS. pneumoniae 13.3 mg/l (range 8–128 mg/l), and ofNeisseria includingB. catarrhalis 27.0 mg/l (range 16–128 mg/l). The MBCs were very close to the MICs.

---

In-vitro-Aktivität von Fosfomycin gegen Haemophilus influenzae, Streptococcus pneumoniae und Neisseriaspecies

Zusammenfassung Die minimalen Hemmkonzentrationen (MHK) und minimalen bakteriziden Konzentrationen (MBK) von Fosfomycin wurden mittels einer Agardilutionstechnik für je 100 Stämme vonHaemophilus influenzae undStreptococcus pneumoniae und 40 Stämme vonNeisseria species undBranhamella catarrhalis bestimmt. Die mittlere MHK vonH. influenzae war 0,13 mg/l (Bereich 0,008–64 mg/l), vonS. pneumoniae 13,3 mg/l (Bereich 8–128 mg/l) und vonNeisseria einschließlichB. catarrhalis 27,0 mg/l (Bereich 16–128 mg/l). Die MBKs lagen sehr nahe an den MHKs.

---

---

This paper is dedicated to Professor Walter Marget in honour of his 60th birthday.     

Growth of Haemophilus influenzae in human milk: synthesis, distribution, and activity of IgA protease as determined by study of iga+ and mutant iga- cells.

The nonencapsulated, IgA protease-positive Haemophilus influenzae strain Rd and serogroup b clinical isolates were found to proliferate in human milk. Growth did not require supplemental X and V factors. In milk, strain Rd synthesized IgA protease, but it was completely inhibited by antibody, so secretory IgA in milk cultures remained intact. Inhibition was largely attributable to IgA1 antibodies. Rd cells also aggregated during growth in milk and showed colony size variation, whereas a protease-negative mutant of Rd (Rd225DK) aggregated less and had uniform colony size. Like differences in protease inhibition, these differences in growth pattern were mediated by secretory IgA1. Thus, milk antibody not only inhibited the extracellular protease but also interacted directly with the enzyme precursor or related antigens on growing bacterial cells. This self-protective property of milk secretory IgA may be an important immunologic attribute for the upper respiratory mucosa of the infant.     

Human milk lactoferrin inactivates two putative colonization factors expressed by Haemophilus influenzae

Haemophilus influenzae is a major cause of otitis media and other respiratory tract disease in children. The pathogenesis of disease begins with colonization of the upper respiratory mucosa, a process that involves evasion of local immune mechanisms and adherence to epithelial cells. Several studies have demonstrated that human milk is protective against H. influenzae colonization and disease. In the present study, we examined the effect of human milk on the H. influenzae IgA1 protease and Hap adhesin, two autotransported proteins that are presumed to facilitate colonization. Our results demonstrated that human milk lactoferrin efficiently extracted the IgA1 protease preprotein from the bacterial outer membrane. In addition, lactoferrin specifically degraded the Hap adhesin and abolished Hap-mediated adherence. Extraction of IgA1 protease and degradation of Hap were localized to the N-lobe of the bilobed lactoferrin molecule and were inhibited by serine protease inhibitors, suggesting that the lactoferrin N-lobe may contain serine protease activity. Additional experiments revealed no effect of lactoferrin on the H. influenzae P2, P5, and P6 outer-membrane proteins, which are distinguished from IgA1 protease and Hap by the lack of an N-terminal passenger domain or an extracellular linker region. These results suggest that human milk lactoferrin may attenuate the pathogenic potential of H. influenzae by selectively inactivating IgA1 protease and Hap, thereby interfering with colonization. Future studies should examine the therapeutic potential of lactoferrin, perhaps as a supplement in infant formulas.     

Selective procedure to isolate Haemophilus influenzae from sputa with large quantities of pseudomonas aeruginosa

Summary The identification of respiratory pathogens (e. g.Haemophilus influenzae, Streptococcus pneumoniae) is impaired by the presence of large quantities ofPseudomonas aeruginosa, as is the case in the sputum specimens of cystic fibrosis patients. A procedure has been evaluated whereby the selective inhibition of the proliferation ofP. aeruginosa is achieved by a broad spectrum pyocin, whereas the growth ofH. influenzae is not influenced. This technique has been tested over a two year period resulting in a significantly augmented rate of identification ofH. influenzae.

---

Verfahren zur Selektivkultur von Haemophilus influenzae in Gegenwart von Pseudomonas aeruginosa

Zusammenfassung Bei Infektionen der unteren Atemwege kann der Nachweis vonHaemophilus influenzae oderStreptococcus pneumoniae in Gegenwart hoher Konzentrationen vonPseudomonas aeruginosa erschwert sein (z. B. bei Mukoviscidose). Spezifische Hemmung desP. aeruginosa-Wachstums ohne Beeinträchtigung der Vermehrung vonH. influenzae läßt sich mit Pyocinen breiten Hemmspektrums erreichen. Daraus wurde ein Verfahren zum selektivenH. influenzae-Nachweis entwickelt. Bei etwa zweijährigem Einsatz dieser Methode konnte die Nachweishäufigkeit vonH. influenzae inP. aeruginosa-haltigen Sputa von Mukoviscidosepatienten verdoppelt werden.

     

Characterization of clinical isolates of haemophilus influenzae type b for heterogeneous populations of susceptibility to ampicillin

Summary In this study 80 clinical isolates ofHaemophilus influenzae type b from 60 patients were used to analyze if heterogeneous populations of ampicillin resistant and sensitive cells were simultaneously present within each strain and to determine how common this phenomenon was among clinical isolates. A total of 50 ampicillin sensitive clinical isolates were screened for resistance to this antibiotic. It was observed that 32 ampicillin sensitive strains did not contain resistant subpopulations. Furthermore, even with the inducement of resistant subgroups to proliferate under antibiotic-mediated selection using maximum subinhibitory concentrations of ampicillin, no subpopulations of resistant cells were discovered among 18 additional strains. In order to determine whether ampicillin resistance was stable in -lactamase-producingH. influenzae clinical isolates, 20 strains from 16 patients were examined. No tendency to segregate into a heterogeneous population of sensitive and resistant clones was found. Furthermore, ampicillin resistance was still uniformly expressed after the treatment of ten strains with the curing agent acridine orange. These results suggest that after extensive evaluation no heterogeneous populations existed with ampicillin resistant and sensitiveH. influenzae clinical isolates, indicating that this phenomenon is not a prevalent one.

---

Untersuchung klinischer Isolate von Haemophilus influenzae Typ b auf heterogene Populationen bezüglich Ampicillinempfindlichkeit

Zusammenfassung In der vorliegenden Studie wurden 80 klinische Isolate vonHaemophilus influenzae Typ b von 60 Patienten untersucht, um festzustellen, ob im selben Stamm heterogene Populationen von ampicillinresistenten und ampicillinempfindlichen Zellen vorhanden sind und wie häufig dieses Phänomen in klinischen Isolaten ist. Insgesamt wurden 50 ampicillinempfindliche Isolate auf eine Resistenz gegen dieses Antibiotikum untersucht. Unter 32 ampicillinempfindlichen Isolaten fanden sich keine resistenten Subpopulationen. Selbst mit Methoden zur Induktion resistenter Subpopulationen durch Antibiotika-vermittelte Selektion unter Verwendung maximaler subinhibitorischer Konzentrationen von Ampicillin wurden in 18 weiteren Stämmen keine Subpopulationen von resistenten Zellen entdeckt. 20 Stämme von 16 Patienten wurden untersucht, um festzustellen, ob in klinischen Isolaten von -Lactamase bildendenH. influenzae eine stabile Ampicillinresistenz bestand. Eine Tendenz zur Segregation in eine heterogene Population empfindlicher und resistenter Stämme konnte nicht festgestellt werden. Nach Behandlung von zehn Stämmen mit Akridinorange wurde weiterhin gleichförmig Ampicillinresistenz exprimiert. Da umfassende Untersuchungen keine heterogenen Populationen ampicillinresistenter und ampicillinempfindlicher Zellen in klinischen Isolaten vonH. influenzae aufdeckten, ist anzunehmen, daß dieses Phänomen nicht vorrangig ist.

     

In vitro activity of Ro 15-8074 and Ro 19-5247 in comparison to cefaclor and cefalexin

Summary 805 clinical isolates were investigated for theirin vitro sensitivity against Ro 15-8074 and Ro 19-5247 in comparison to cefaclor and cefalexin in a serial dilution test on solid medium. Ro 19-5247 had the strongest activity of all drugs tested against streptococci (exceptStreptococcus faecalis) and was as active as cefaclor and cefalexin against most strains ofStaphylococus aureus. Ro 19-5247 was the only oral cephalosporin active againstBordetella pertussis. It was on average 160 times more active than cefaclor againstHaemophilus influenzae. In its activity against enterobacteria Ro 19-5247 was always superior to cefaclor and cefalexin. Only a few strains ofEnterobacter aerogenes, Enterobacter cloacae, Klebsiella pneumoniae, Proteus vulgaris andSerratia marcescens were resistant to Ro 19-5247 as were all strains ofEnterobacter agglomerans andKlebsiella ozaenae. Ro 15-8074 was inactive against staphylococci but ten times more active than cefaclor and cefalexin againstStreptococcus pyogenes. There was no difference in the activity againstStreptococcus pneumoniae andStreptococcus agalactiae. AgainstHaemophilus influenzae Ro 15-8074 acted 12 times stronger than cefaclor and 100 times stronger than cefalexin. The activity against enterobacteria corresponded to that of Ro 19-5247. Ro 15-8074 was also active against most strains ofEnterobacter cloacae andProteus vulgaris which were resistant to cefaclor and cefalexin.

---

In vitro-Aktivität von Ro 15-8074 und Ro 19-5247 im Vergleich zu Cefaclor und Cefalexin

Zusammenfassung 805 klinische Isolate wurden im Reihenverdünnungsversuch mit den neuen Oralcephalosporinen Ro 15-8074 und Ro 19-5274 im Vergleich zu Cefaclor und Cefalexin geprüft. Ro 19-5247 hatte die stärksteIn vitro-Aktivität gegen Streptokokken (mit Ausnahme vonStreptococcus faecalis) und war gegen die meistenStaphylococcus aureus-Stämme ebenso wirksam wie Cefaclor und Cefalexin. Ro 19-5247 wirkte als einziges Oralcephalosporin gegenBordetella pertussis. Es war gegenHaemophilus influenzae im Durchschnitt 160fach stärker als Cefaclor. Bei Enterobakterien war Ro 19-5247 dem Cefaclor und Cefalexin stets überlegen. Resistent waren wenige Stämme vonEnterobacter aerogenes, Enterobacter cloacae, Klebsiella pneumoniae, Proteus vulgaris undSerratia marcescens sowie alle Stämme vonEnterobacter agglomerans undKlebsiella ozaenae. Ro 15-8074 war gegen Staphylokokken in therapeutischen Konzentrationen immer unwirksam. Es wirkte gegenStreptococcus pyogenes zehnfach stärker als Cefaclor und Cefalexin, während beiStreptococcus pneumoniae undStreptococcus agalactiae kein Unterschied bestand. GegenHaemophilus influenzae wirkte Ro 15-8074 im Durchschnitt 12fach stärker als Cefaclor und 100fach stärker als Cefalexin. Bei Enterobakterien entsprach die Wirksamkeit von Ro 15-8074 etwa der von Ro 19-5247. Es wirkte auch gegen die meisten Stämme vonEnterobacter cloacae undProteus vulgaris, bei denen Cefaclor und Cefalexin unwirksam waren.

     

Antibiotic Resistance in Sputum Isolates of Streptococcus pneumoniae in Chronic Obstructive Pulmonary Disease is Related to Antibiotic Exposure

ABSTRACT

Streptococcus pneumoniae (S. pneumoniae) is recovered from sputum of patients with chronic obstructive pulmonary disease (COPD) during stable disease and exacerbations. In patients with community acquired pneumonia, antibiotic exposure in the prior 3–6 months is associated with recovery of antibiotic resistant isolates of S. pneumoniae. Whether the same relationship is seen in COPD is not known. From April 1994 to June 2004, 127 adults with COPD were enrolled in a prospective longitudinal study. Sputum isolates of S. pneumoniae were characterized with susceptibility testing and pulsed-field gel electrophoresis (PFGE). The relationship between antibiotic use in the previous 3 and 6 months with either new acquisition of a resistant pneumococcal isolate or development of resistance (4-fold increase in MIC) in a pre-existing colonizing pneumococcal strain was determined. A total of 194 pneumococcal isolates were recovered from 38 patients. Among 71 newly acquired and 4 resistance-emergent strains analyzed further, rates of resistance to penicillin (MIC ≥2), erythromycin (MIC ≥1), tetracycline (MIC ≥8) and trimethoprim/sulfamethoxazole (MIC ≥4) were 8%, 24%, 17% and 16% respectively. Flouroquinolone resistance was not seen. Among strains isolated from patients exposed to a macrolide within 6 months, 53.6% displayed erythromycin resistance vs. 14% of strains without such exposure (p = 0.00085). Similar associations were not seen for other antibiotics. Macrolide use in the previous 6 months is associated with macrolide resistance in sputum isolates of S. pneumoniae. Recent antibiotic exposure may help in determining appropriate antibiotic treatment in these patients.     

Molecular polymorphism and epidemiology of Neisseria meningitidis immunoglobulin A1 proteases.

Neisseria meningitidis is one of several important bacterial pathogens that secrete a specific protease capable of cleaving human immunoglobulin A1 (IgA1) in the hinge region. To obtain further information on this putative virulence factor, we examined the IgA1 protease and iga gene region of 133 isolates of N. meningitidis assigned to 88 multilocus enzyme genotypes and representing major epidemics and carrier strains from 19 countries. Of the two IgA1 cleavage specificities previously observed, isolates associated with epidemics of meningococcal disease showed exclusively type 1 IgA1 protease activity. Considerable heterogeneity of the N. meningitidis IgA1 protease was demonstrated at both the protein and gene levels. Thus, five different forms of IgA1 protease were detected with enzyme-neutralizing antibodies raised in rabbits. An antiserum raised against a single type 2 IgA1 protease inhibited the enzyme activity of all strains examined, a finding of potential significance for the possible application of IgA1 protease in a vaccine against meningococcal disease. Examination of the iga gene region with restriction endonucleases revealed a high degree of polymorphism among strains belonging to some multilocus enzyme genotypes. The different iga gene types did not correlate with cleavage type or inhibition of the IgA1 protease. Our findings indicate that horizontal genetic exchange occurs in vivo with considerably different frequency in different clones of meningococci.     

Etiology and Antimicrobial Susceptibility of Middle Ear Fluid Pathogens in Costa Rican Children With Otitis Media Before and After the Introduction of the 7-Valent Pneumococcal Conjugate Vaccine in the National Immunization Program: Acute otitis media microbiology in Costa Rican children

Acute otitis media (AOM) microbiology was evaluated in children after 7-valent pneumococcal conjugate vaccine (PCV7) introduction in Costa Rica (private sector, 2004; National Immunization Program, 2009).This was a combined prospective and retrospective study conducted in a routine clinical setting in San José, Costa Rica. In the prospective part of the study, which was conducted post-PCV7 introduction (2010–2012), standard bacteriological procedures were used to evaluate the etiology and serotype distribution of middle ear fluid samples collected by tympanocentesis or otorrhea from children aged 3–59 months diagnosed with AOM. E-tests were used to evaluate antimicrobial susceptibility in culture-positive samples. Retrospective data recorded between 1999 and 2004 were used for comparison of bacterial etiology and serotype distribution before and after PCV7 introduction. Statistical significance was evaluated in bivariate analyses at the P-value < 0.05 level (without multiplicity correction).Post-PCV7 introduction, Haemophilus influenzae was detected in 118/456 and Streptococcus pneumoniae in 87/456 AOM episodes. Most H. influenzae isolates (113/118) were non-typeable. H. influenzae was more (27.4% vs 20.8%) and S. pneumoniae less (17.1% vs 25.5%) frequently observed in vaccinated (≥2 PCV7 doses or ≥1 PCV7 dose at >1 year of age) versus unvaccinated children. S. pneumoniae non-susceptibility rates were 1.1%, 34.5%, 31.7%, and 50.6% for penicillin, erythromycin, azithromycin, and trimethoprim/sulfamethoxazole (TMP-SMX), respectively. H. influenzae non-susceptibility rate was 66.9% for TMP-SMX. Between pre- and post-PCV7 introduction, H. influenzae became more (20.5% vs 25.9%; P-value < 0.001) and S. pneumoniae less (27.7% vs 19.1%; P-value = 0.002) prevalent, and PCV7 serotype proportions decreased among pneumococcal isolates (65.8% vs 43.7%; P-value = 0.0005). Frequently identified pneumococcal serotypes were 19F (34.2%), 3 (9.7%), 6B (9.7%), and 14 (9.7%) pre-PCV7 introduction, and 19F (27.6%), 14 (8.0%), and 35B (8.0%) post-PCV7 introduction.Following PCV7 introduction, a change in the distribution of AOM episodes caused by H. influenzae and pneumococcal serotypes included in PCV7 was observed in Costa Rican children. Pneumococcal vaccines impact should be further evaluated following broader vaccination coverage.     

Ceforanide (BL-S 786) in the treatment of community-acquired bacterial pneumonia

Summary Ceforanide (BL-S 786) is a new long-acting parenteral cephalosporin which has the major pharmacologic advantage of requiring only twice a day dosage. We treated 28 adult patients with community-acquired bacterial pneumonia using doses of 500 or 1000 mg every 12 hours. Twenty-four of 28 infections were due toStreptococcus pneumoniae and/orHemophilus influenzae, and all pathogens were susceptible in vitro to both cephalothin and ceforanide. Patients were treated for a mean of 7.5 days, and all showed a good clinical and radiographic response with no mortality. Of the 13 patients withH. influenzae, the organism could still be recovered during therapy in 9/12 and post therapy in 3/8. One clinical superinfection (sepsis due toPseudomonas aeruginosa) occurred during therapy. Side effects with therapy included thrombocytosis (15), asymptomatic eosinophilia (5), and mild elevation of the serum transaminases (3). These studies suggest that ceforanide is a safe and effective agent for the treatment of adult patients with bacterial pneumonia due toS. pneumoniae; further experience in therapy ofH. influenzae is needed because of frequent failure of ceforanide to eradicate this organism from the sputum.

---

Ceforanid (BL-S 786) in der Behandlung der nicht im Krankenhaus erworbenen bakteriellen Pneumonie

Zusammenfassung Ceforanid (BL-S 786) ist ein neues, lang wirkendes parenterales Cefalosporin, das den wesentlichen pharmakologischen Vorteil hat, daß es nur zweimal am Tag verabreicht werden muß. Wir behandelten 28 erwachsene Patienten mit nicht im Krankenhaus erworbener bakterieller Pneumonie, dabei wurden Dosen von 500 mg oder 1000 mg alle 12 Stunden gegeben. Vierundzwanzig der 28 Infektionen waren durchStreptococcus pneumoniae und/oderHaemophilus influenzae verursacht, und alle pathogenen Erreger waren in vitro empfindlich gegenüber Cefalothin und Ceforanid. Die Kranken wurden im Durchschnitt 7,5 Tage lang behandelt, alle zeigten einen guten klinischen und röntgenologischen Therapieerfolg, keiner verstarb. Von den 13 Patienten mitHaemophilus influenzae konnte der Organismus während der Therapie noch bei 9/12 und nach Abschluß der Therapie noch bei 3/8 gefunden werden. Unter der Behandlung kam es in einem Fall zu einer klinischen Superinfektion (Sepsis durchPseudomonas aeruginosa). Nebenwirkungen der Therapie umfaßten Thrombozytose (15), asymptomatische Eosinophilie (5) und leichte Erhöhung der Serum-Transaminasen (3). Die vorgelegten Untersuchungen lassen annehmen, daß Ceforanid ein sicheres und wirksames Mittel für die Behandlung erwachsener Patienten mit bakterieller Pneumonie durchS. pneumoniae ist; in der Behandlung vonH. influenzae bedarf es noch weiterer Erfahrung, da es unter Ceforanid häufig nicht gelungen ist, diesen Erreger aus dem Sputum zu beseitigen.

     

Spread ofklebsiella pneumoniae producing SHV-5 beta-lactamase among hospitalized patients

Summary The first outbreak of infections caused by an SHV-5 producing strain ofKlebsiella pneumoniae is reported. Within a period of 1 year and 9 months, multiresistantK. pneumoniae strains caused severe infections, mostly of the lower respiratory tract, in 22 patients. The strains were resistant to penicillins, third-generation cephalosporins, aztreonam, chloramphenicol, tetracycline and co-trimoxazole. The resistance determinants were transferable toEscherichia coli. All isolates produced a beta-lactamase with a pI of 8.2. Ceftazidime was hydrolyzed at this band. These characteristics, together with the resistance phenotype, are identical to those of a reference strain producing the beta-lactamase SHV-5. TheK. pneumoniae strains of all patients were identical in their capsular serotype (K1), plasmid pattern and plasmid fingerprint after digestion with Dra I restriction endonuclease. We conclude that this outbreak was caused by the spread of one clone ofK. pneumoniae producing SHV-5 beta-lactamase among patients of different wards. Our results indicate a real risk for failure of therapy by third-generation cephalosporins in intensive care patients due to SHV-5 producing pathogens.

---

Ausbreitung eines SHV-5-betalaktamase-produzierenden Stammes von Klebsiella pneumoniae unter hospitalisierten Patienten

Zusammenfassung Wir berichten über das in Deutschland erstmalig gehäufte Auftreten von Infektionen verursacht durch einen Stamm vonKlebsiella pneumoniae, der die plasmidische Betalaktamase SHV-5 produziert. Innerhalb eines Beobachtungszeitraumes von einem Jahr und neun Monaten verursachte dieser Stamm bei 22 Patienten schwere nosokomiale Infektionen zumeist der tiefen Atemwege. Der Erreger war resistent gegenüber Penicillinen, Cephalosporinen der dritten Generation, Aztreonam, Chloramphenicol, Tetrazyklin und Co-trimoxazol. Die Resistenzdeterminanten waren aufEscherichia coli übertragbar. Alle Isolate produzierten eine Betalaktamase mit einem isoelektrischen Punkt von 8,2, die Ceftazidim hydrolysierte. Diese Merkmale zusammen mit dem Resistenz-Phänotyp sind identisch mit denen eines mitgeführten Referenzstammes, der die Betalaktamase SHV-5 produziert. AlleK. pneumoniae-Stämme waren identisch in ihrem Kapsel-Serotyp, ihrem Plasmidmuster und ihrem Plasmid-Fingerprint (nach Verdauen mit der Restriktionsendonuclease Dra I). Wir schließen daraus, daß dieser Ausbruch von Infektionen durch einen einzigen Klon eines betalaktamase-produzierendenK. pneumoniae-Stammes verursacht wurde, der sich über verschiedene Stationen verbreitete. Diese Ergebnisse signalisieren das Risiko von Therapiemißerfolgen in Deutschland bei empirischem Einsatz von Drittgenerations-Cephalosporinen bei Infektionen mitK. pneumoniae.

     

Bactericidal effect of sparfloxacin alone and in combination with amoxicillin againstStreptococcus pneumoniae as determined by kill-kinetic studies

Summary Ten clinical isolates ofStreptococcus pneumoniae (six intermediately penicillin-sensitive, one penicillin-resistant and three penicillin-sensitive strains) were studied by kill-kinetic experiments using sparfloxacin alone and in combination with amoxicillin. Equipotent doses of the antibiotics (1x, 2x and 4x the MIC) were used in the kill-kinetic studies. Sparfloxacin had a moderate bactericidal potential at 4x MIC after 5 h and the combination with amoxicillin did not significantly increase its bactericidal activity. The clinical significance of these findings warrants further studiesin vivo.

---

Bakterizider Effekt von Sparfloxacin allein und in Kombination mit Amoxicillin gegenStreptococcus pneumoniae in Studien zur Abtötungskinetik

Zusammenfassung Zehn klinische Isolate vonStreptococcus pneumoniae (sechs mäßig Penicillin G empfindliche, ein penicillin-resistenter, drei penicillin-empfindliche Stämme), wurden in Experimenten zur Abtötungskinetik mit Amoxicillin untersucht. In den Experimenten wurden äquipotente Dosen der Antibiotika (1x, 2x, 4x MHK) verwendet. Sparfloxacin zeigte eine mäßig bakterizide Wirkung 4x MHK bei Stunde 5, und die Kombination mit Amoxicillin vermehrte seine bakterizide Wirksamkeit nicht signifikant. Die klinische Bedeutung dieser Befunde muß inIn-vivo-Studien weiter untersucht werden.

     

Early synergistic killing activity at concentrations attainable in CSF of amoxicillin or cefotaxime and aminoglycosides against Haemophilus influenzae

Summary Rapid eradication of bacteria from the CSF is critical for the outcome ofHaemophilus influenzae meningitis in children. In 15 patients studied, the meanH. influenzae colony counts in CSF were 10⁵ CFU/ml (range: 10² to 10⁹ CFU/ml). Time-kill curves were determined for amoxicillin and cefotaxime alone and in combination with gentamicin or amikacin, against 60 clinical isolates ofH. influenzae at concentrations equivalent to those found in CSF following systemic administration. Against -lactamase-negative strains (n=44) a bactericidal effect was observed at 18 h for amoxicillin alone, at 5 h for amoxicillin plus aminoglycosides and at 2.5 h for cefotaxime with or without aminoglycosides. Against -lactamase-positive strains a bactericidal effect was observed at 18 h for cefotaxime, at 5 h for amoxicillin plus aminoglycosides and at 2.5 h for cefotaxime plus aminoglycosides. It appears that despite low concentrations of gentamicin or amikacin in the CSF, the accelerated killing ofH. influenzae provides a rationale for the initial use of the combination of cefotaxime and aminoglycosides in the initial treatment ofH. influenzae meningitis.

---

Frühe synergistische bakterizide Wirkung von Amoxicillin oder Cefotaxim in Kombination mit Aminoglykosiden in im Liquor erreichbaren Konzentrationen gegen Haemophilus influenzae

Zusammenfassung Für den Verlauf derHaemophilus influenzae-Meningitis bei Kindern ist die rasche Elimination der Bakterien aus dem Liquor entscheidend. Bei 15 Patienten wurden die Koloniebildnerzahlen vonH. influenzae im Liquor bestimmt; sie betrugen im Mittel 10⁵ KBE/ml (Bereich 10² bis 10⁹ KBE/ml). Für Amoxicillin und Cefotaxim allein und in Kombination mit Gentamicin oder Amikacin wurde die bakterizide Wirkung gegen 60 klinische Isolate vonH. influenzae in ihrem zeitlichen Ablauf untersucht; dabei kamen Konzentrationen zur Anwendung, die den nach systemischer Applikation im Liquor gefundenen Spiegeln entsprechen. Amoxicillin allein zeigte gegen -Laktamase-negative Stämme (n=44) nach 18 Stunden einen bakteriziden Effekt, die Kombination von Amoxicillin und Aminoglykosiden nach 5 Stunden und Cefotaxim allein oder in Kombination mit Aminoglykosiden nach 2,5 Stunden. Gegen -Lactamase bildende Stämme wurde mit Cefotaxim allein nach 18 Stunden, mit Amoxicillin in Kombination mit Aminoglykosiden nach 5 Studen und mit Cefotaxim plus Aminoglykosiden nach 2,5 Stunden eine bakterizide Wirkung beobachtet. Obwohl Gentamicin oder Amikacin im Liquor nur niedrige Spiegel erreichen, läßt sich aus der beschleunigten Abtötung vonH. influenzae ein wohlbegründetes Therapiekonzept für die Anwendung von Cefotaxim in Kombination mit Aminoglykosiden in der Initialtherapie derH. influenzae-Meningitis ableiten.

     

Bacteria and viruses that cause respiratory tract infections during the pilgrimage (Haj) season in Makkah,Saudi Arabia

objective To determine the incidence and type of RTI-causing bacteria and viruses during a period of epidemic infections. method A total of 395 sputum specimens and 761 throat swabs were collected during the 1991 and 1992 pilgrimage seasons (Haj to Makkah Al-Mukarama, Saudi Arabia) from patients referred to one hospital and three dispensaries with symptoms of respiratory tract infections. All 761 throat swabs of both Haj seasons were also screened for the presence of viral pathogens with monoclonal antibodies specific for 7 viruses known to cause respiratory infections. results Bacterial pathogens were detected in 118 (29.9%) specimens. During the 1991 Haj season Haemophilus influenzae was the most frequent bacterial pathogen detected (10%), followed by Klebsiella pneumoniae (5.2%), Streptococcus pneumoniae (4.8%), Staphylococcus aureus (3.8%) and Streptococcus pyogenes (2.4%). In the 1992 Haj season Klebsiella pneumoniae was predominant (15.1%), followed by Haemophilus influenzae and Streptococcus pneumoniae (12.3%). Screening of all sputum specimens for acid-fast bacteria showed that the overall incidence rate of tuberculosis was 1%. Cultures from the 761 throat swabs were largely negative for bacteria except for Streptococcus pyogenes isolated from 7 patients. Viruses were detected in 148 (19.5%) specimens with influenza A and adenovirus being the most common viruses. conclusion The pattern of virus prevalence in the 1991 and 1992 pilgrimage seasons was identical: influenza A and adenovirus predominated. Thus these two viruses should be targeted in future prophylactic measures.     

Antibody Reactivity of a Standardized Human Serum Protein Solution Against a Spectrum of Microbial Pathogens and Toxins: Comparison with Fresh Frozen Plasma

Abstract: In this study, we compared a standardized solution of human serum protein (HSP) and fresh frozen plasma (FFP) with regard to the antibody specificity against a number of microbial pathogens and some important pathogenicity factors of bacterial pathogens. Due to the clinical use of HSP and FFP for therapeutical plasma exchange, we have chosen a spectrum of microbial pathogens for serological analysis that is critical in clinical settings. With the enzyme‐linked immunosorbent assay technique, we could show that HSP contains marked IgG antibody reactivity against antigens of Escherichia coli, Campylobacter jejuni, Enterobacter sakazakii, Proteus mirabilis, Pseudomonas aeruginosa, Klebsiella pneumoniae, Staphylococcus aureus, S. epidermidis, Streptococcus pneumoniae, Enterococcus faecalis, Chlamydia pneumoniae, and Candida albicans. Although no IgM antibodies against the pathogens tested could be detected in HSP, moderate IgA reactivity was found against 4 of 12 microbial antigens. Immunoblot analysis demonstrated specific IgA and IgG responses against the endoproteinase Glu‐C and the superantigens enterotoxin A and B of S. aureus, the IgA‐protease of Neisseria gonorrhoeae, and Shiga toxin 2 of enterohemorrhagic E. coli. By using 3 different HSP batches in parallel, we could demonstrate antibody reactivity against important microbial pathogens and toxins. This antibody profile is essentially more homogeneous than that of 3 batches of FFP.     

Serotypes and antimicrobial susceptibility of Streptococcus pneumoniae in west Germany

Summary Two-hundred-and-six strains ofStreptococcus pneumoniae were isolated in eight centers in West Germany. The prevalent serotypes were: 19, 3, 6, 7, 23 and 15. Seventy-five percent of the strains tested were antigenically identical to the pneumococcal types included in the 14-valent vaccine Pneumovax®. Susceptibility testing revealed resistance to tetracycline (11% of the isolates), co-trimoxazole (7%) and chloramphenicol (2%). Seven percent of the isolates were relatively resistant to penicillin (MIC 0.1–1.0 mg/l).

---

Serotypen und Resistenzverhalten von Streptococcus pneumoniae in der Bundesrepublik Deutschland

Zusammenfassung In einer multizentrischen Studie wurden insgesamt 206 Stämme vonStreptococcus pneumoniae aus acht Instituten in der Bundesrepublik Deutschland untersucht. Die vorherrschenden Serotypen waren 19, 3, 6, 7, 23 und 15. 75% aller isolierten Stämme besitzen das Antigen, das auch in der 14 Polysaccharid-Antigene umfassenden Vakzine Pneumovax® enthalten ist. Bei der Bestimmung der minimalen Hemmkonzentration zeigten 11% der Isolate Resistenz gegen Tetracyclin, 7% gegen Co-Trimoxazol und 2% gegen Chloramphenicol. 7% der Stämme zeigten eine relative Resistenz gegenüber Penicillin (MHK 0,1–1,0 mg/l).

     

Recurrent Posttraumatic Meningitis due to Nontypable <Emphasis Type="Italic">Haemophilus influenzae</Emphasis>: Case Report and Review of the Literature

Abstract We report a case of relapsing Haemophilus influenzae meningitis in a boy at the age of nearly 3 years and 4.2 years who had been successfully vaccinated against H. influenzae serotype b (Hib). The pathogen was a nonencapsulated (nontypable) H. influenzae strain of biotypes III and VI, respectively. A rhinobasal impalement injury with development of a posttraumatic encephalocele is considered to be the predisposing condition. Review of the literature reveals that in patients systemically infected by nonencapsulated H. influenzae strains predisposing factors such as cerebrospinal fluid-shunts, implants and traumas are often found. To obtain further information on potential new disease patterns H. influenzae isolates from cerebrospinal fluid should be examined for capsule production and, if relevant, further characterized by capsular typing.     

Pneumonia in a nursing home

The authors studied nursing home residents serologically to determine whether atypical organisms were causes of radiologic pneumonia. The study was conducted at the Wisconsin Veterans Home, a facility with on-site microbiology and x-ray. Over one year, serologic examinations for Legionella, Mycoplasma, and Chlamydia were conducted for the residents who had pneumonia. Cultures and mortality were reviewed. Fifty-six episodes were studied (mean resident age 78 years). There was no fourfold titer change. Seventeen quality sputum specimens revealedStreptococcus pneumoniae (5), normal flora (4),Hemophilus influenzae (4),Moraxella catarrbalis (3),Staphylococcus aureus (1), and beta-hemolytic Streptococcus, not group A (1). The two-month mortality was 21%. This study did not result in serologic confirmation of atypical organisms’ causing pneumonia. Antibiotic choice should be based on coverage of prevalent organisms, includingHemophilus influenzae, Moraxella, and Staphylococcus, as well as clinical features.     

Changing epidemiology of bacterial meningitis

Immunization against the most common meningeal pathogens is the leading factor associated with decreased incidence of bacterial meningitis in countries where routine vaccination is available. This is most dramatically illustrated by the reduction in the incidence of Haemophilus influenzae type b meningitis. The incidence of bacterial meningitis has decreased by 55% since the introduction of the H. influenzae type b conjugate vaccine in 1990. H. influenzae occurred primarily in children younger than 5 years of age, and so the median age of patients with bacterial meningitis has now increased to 39 years of age in the United States, and the leading pathogen is currently Streptococcus pneumoniae. Three other control measures (ie, universal screening and antibiotic prophylaxis of pregnant women for Group B streptococci and the implementation and availability of the S. pneumoniae and Neisseria meningitidis conjugate vaccines) have likely further decreased the incidence of these meningeal pathogens. Lastly, the worldwide emergence of multidrug-resistant pneumococci has complicated the empiric therapy of bacterial meningitis.     

Ceftaroline activity tested against contemporary Latin American bacterial pathogens (2011)

A total of 2484 target bacterial pathogens were collected (one per patient episode) from patients in 16 Latin American medical centers located in seven nations during 2011. Isolate identity was confirmed at a coordinating laboratory and susceptibility testing was performed for ceftaroline and comparator agents according to reference broth microdilution methods. A total of 30.0% of isolates were from respiratory tract, 29.4% from skin and skin structure, 21.4% from blood stream, 7.9% from urinary tract and 11.3% from other sites. Ceftaroline was active against Staphylococcus aureus (42.8% MRSA) with 83.6% of the isolates at ≤1 mg/L and all isolates at ≤2 mg/L (MIC₅₀₉₀, 0.25/2 mg/L). National MRSA rates ranged from a low of 28.8% in Colombia to a high of 68.1% in Chile. All Streptococcus pyogenes and Streptococcus agalactiae were susceptible to ceftaroline (MIC_50/90 values were at ≤0.015/≤0.015 mg/L for both). All Streptococcus pneumoniae were susceptible to ceftaroline, linezolid, tigecycline and vancomycin. Susceptibility to ceftriaxone was at 88.4% (CLSI non-meningitis interpretive criteria) and 73.9% (CLSI meningitis interpretive criteria) for all S. pneumoniae. Ceftriaxone susceptibility was only at 33.3% (CLSI non-meningitis interpretive criteria) and 0.0% (CLSI meningitis interpretive criteria) for penicillin-intermediate (penicillin MIC, 4 mg/L) strains. All Haemophilus influenzae (29.4% β-lactamase-positive) isolates were susceptible to ceftaroline, amoxicillin–clavulanate, ceftriaxone, and levofloxacin. For the Latin American region, the ESBL-phenotype rate was 37.6% for Escherichia coli and 53.3% for Klebsiella pneumoniae. Ceftaroline was not active against ESBL-phenotype strains but was active against >90.0% of the non-ESBL-phenotype. The spectrum of activity of ceftaroline against pathogens from Latin America indicates that it merits further study for its potential use in the Latin American region.