Comparative antibody and cell-mediated immune responses, reactogenicity, and efficacy of homologous and heterologous boosting with CoronaVac and BNT162b2 (Cobovax): an open-label, randomised trial.

BACKGROUND: Few trials have compared homologous and heterologous third doses of COVID-19 vaccination with inactivated vaccines and mRNA vaccines. The aim of this study was to assess immune responses, safety, and efficacy against SARS-CoV-2 infection following homologous or heterologous third-dose COVID-19 vaccination with either one dose of CoronaVac (Sinovac Biotech; inactivated vaccine) or BNT162b2 (Fosun Pharma-BioNTech; mRNA vaccine). METHODS: This is an ongoing, randomised, allocation-concealed, open-label, comparator-controlled trial in adults aged 18 years or older enrolled from the community in Hong Kong, who had received two doses of CoronaVac or BNT162b2 at least 6 months earlier. Participants were randomly assigned, using a computer-generated sequence, in a 1:1 ratio with allocation concealment to receive a (third) dose of CoronaVac or BNT162b2 (ancestral virus strain), stratified by types of previous COVID-19 vaccination (homologous two doses of CoronaVac or BNT162b2). Participants were unmasked to group allocation after vaccination. The primary endpoint was serum neutralising antibodies against the ancestral virus at day 28 after vaccination in each group, measured as plaque reduction neutralisation test (PRNT50) geometric mean titre (GMT). Surrogate virus neutralisation test (sVNT) mean inhibition percentage and PRNT50 titres against omicron BA.1 and BA.2 subvariants were also measured. Secondary endpoints included geometric mean fold rise (GMFR) in antibody titres; incidence of solicited local and systemic adverse events; IFNγ+ CD4+ and IFNγ+ CD8+ T-cell responses at days 7 and 28; and incidence of COVID-19. Within-group comparisons of boost in immunogenicity from baseline and between-group comparisons were done according to intervention received (ie, per protocol) by paired and unpaired t test, respectively, and cumulative incidence of infection was compared using Kaplan-Meier curves and a proportional hazards model to estimate hazard ratio. The trial is registered with ClinicalTrials.gov, NCT05057169. FINDINGS: We enrolled participants from Nov 12, 2021, to Jan 27, 2022. We vaccinated 219 participants who previously received two doses of CoronaVac, including 101 randomly assigned to receive CoronaVac (CC-C) and 118 randomly assigned to receive BNT162b2 (CC-B) as their third dose; and 232 participants who previously received two doses of BNT162b2, including 118 randomly assigned to receive CoronaVac (BB-C) and 114 randomly assigned to receive BNT162b2 (BB-B) as their third dose. The PRNT50 GMTs on day 28 against ancestral virus were 109, 905, 92, and 816; against omicron BA.1 were 9, 75, 8, and 86; and against omicron BA.2 were 6, 80, 6, and 67 in the CC-C, CC-B, BB-C, and BB-B groups, respectively. Mean sVNT inhibition percentages on day 28 against ancestral virus were 83%, 96%, 87%, and 96%; against omicron BA.1 were 15%, 58%, 19%, and 69%; and against omicron BA.2 were 43%, 85%, 50%, and 90%, in the CC-C, CC-B, BB-C, and BB-B groups, respectively. Participants who had previously received two doses of CoronaVac and a BNT162b2 third dose had a GMFR of 12 (p<0·0001) compared with those who received a CoronaVac third dose; similarly, those who had received two doses of BNT162b2 and a BNT162b2 third dose had a GMFR of 8 (p<0·0001). No differences in CD4+ and CD8+ T-cell responses were observed between groups. We did not identify any vaccination-related hospitalisation within 1 month after vaccination. We identified 58 infections when omicron BA.2 was predominantly circulating, with cumulative incidence of 15·3% and 15·4% in the CC-C and CC-B groups, respectively (p=0·93), and 16·7% and 14·0% in the BB-C and BB-B groups, respectively (p=0·56). INTERPRETATION: Similar levels of incidence of, presumably, omicron BA.2 infections were observed in each group despite very weak antibody responses to BA.2 in the recipients of a CoronaVac third dose. Further research is warranted to identify appropriate correlates of protection for inactivated COVID-19 vaccines. FUNDING: Health and Medical Research Fund, Hong Kong. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Immunogenicity of a Third Dose of BNT162b2 to Ancestral Severe Acute Respiratory Syndrome Coronavirus 2 and the Omicron Variant in Adults Who Received 2 Doses of Inactivated Vaccine.

BACKGROUND: Limited data exist on antibody responses to mixed vaccination strategies that involve inactivated coronavirus disease 2019 (COVID-19) vaccines, particularly in the context of emerging variants. METHODS: We conducted an open-label trial of a third vaccine dose of a messenger RNA (mRNA) vaccine (BNT162b2, Fosun Pharma/BioNTech) in adults aged ≥30 years who had previously received 2 doses of inactivated COVID-19 vaccine. We collected blood samples before administering the third dose and 28 days later and tested for antibodies to the ancestral virus using a binding assay (enzyme-linked immunosorbent assay [ELISA]), a surrogate virus neutralization test (sVNT), and a live virus plaque reduction neutralization test (PRNT). We also tested for antibodies against the Omicron variant using live-virus PRNT. RESULTS: In 315 participants, a third dose of BNT162b2 substantially increased antibody titers on each assay. Mean ELISA levels increased from an optical density of 0.3 to 2.2 (P < .001), and mean sVNT levels increased from an inhibition of 17% to 96% (P < .001). In a random subset of 20 participants, the geometric mean PRNT50 titers rose substantially, by 45-fold from day 0 to day 28 against the ancestral virus (P < .001) and by 11-fold against the Omicron variant (P < .001). In daily monitoring, post-vaccination reactions subsided within 7 days for more than 99% of participants. CONCLUSIONS: A third dose of COVID-19 vaccine with an mRNA vaccine substantially improved antibody levels against the ancestral virus and the Omicron variant with a well-tolerated safety profile in adults who had received 2 doses of inactivated vaccine 6 months earlier. CLINICAL TRIALS REGISTRATION: NCT05057182.

Slow Waning of Antibodies Following BNT162b2 as a Third Dose in Adults Who Had Previously Received 2 Doses of Inactivated Vaccine.

We administered BNT162b2 as a third dose to 314 adults aged ≥30 years who had previously received 2 doses of inactivated vaccine. We collected blood samples before the third dose and again after 1 month and 6 months, and found robust antibody responses to the ancestral strain at 6 months after receipt of BNT162b2. Antibody responses to Omicron BA.2 by live virus neutralization were weaker after the third dose and had declined to a low level by 6 months.

Homologous and heterologous boosting with CoronaVac and BNT162b2: a randomized trial (the Cobovax study)

BackgroundThere are few trials comparing homologous and heterologous third doses of COVID-19 vaccination with inactivated vaccines and mRNA vaccines. MethodsWe conducted an open-label randomized trial in adults >=18 years of age who received two doses of inactivated vaccine (CoronaVac) or mRNA vaccine (BNT162b2) >=6 months earlier, randomised in 1:1 ratio to receive a third dose of either vaccine. We compared the reactogenicity, immunogenicity and cell-mediated immune responses, and assessed vaccine efficacy against infections during follow-up. ResultsWe enrolled 219 adults who previously received two doses of CoronaVac and randomised to CoronaVac ("CC-C", n=101) or BNT162b2 ("CC-B", n=118) third dose; and 232 adults who previously received BNT162b2 and randomised to CoronaVac ("BB-C", n=118) or BNT162b2 ("BB-B", n=114). There were more frequent reports of mild reactions in recipients of third-dose BNT162b2, which generally subsided within 7 days. Antibody responses against the ancestral virus, Omicron BA.1 and BA.2 subvariant by surrogate neutralization and PRNT50 were stronger for the recipients of a third dose of BNT162b2 over CoronaVac irrespective of prior vaccine type. CD4+ T cells boost only occurred in CoronaVac-primed arms. We did not identify differences in CD4+ and CD8+ T cell responses between arms. When Omicron BA.2 was circulating, we identified 58 infections with cumulative incidence of 15.3% and 15.4% in the CC-C and CC-B (p=0.93), and 16.7% and 14.0% in the BB-C and BB-B arms, respectively (p=0.56). ConclusionsSimilar levels of incidence of infection in each arm suggest all third dose combinations may provide similar degrees of protection against prevalent Omicron BA.2 infection, despite very weak antibody responses to BA.2 in the recipients of a CoronaVac third dose. Further research is warranted to identify appropriate correlates of protection for inactivated COVID-19 vaccines.

BNT162b2 vaccine boosts neutralizing antibodies to ancestral SARS-CoV-2 & Omicron variant in adults who previously received two doses of inactivated vaccine

BackgroundLimited data exist on antibody responses to mixed vaccination strategies involving inactivated COVID-19 vaccines, particularly in the context of emerging variants. MethodsWe conducted an open label trial of a third vaccine dose of an mRNA vaccine (BNT162b2, Fosun Pharma/BioNTech) in adults aged [≥]30 years who had previously received two doses of inactivated COVID-19 vaccine. We collected blood samples before administering the third dose and 28 days later, and tested for antibodies to the ancestral virus using a binding assay (ELISA), a surrogate virus neutralization test (sVNT) and a live virus plaque reduction neutralization test (PRNT). We also tested for antibodies against the Omicron variant using live-virus PRNT. ResultsIn 315 participants, a third dose of BNT162b2 substantially increased antibody titers on each assay. Mean ELISA levels increased from an optical density (OD) of 0.3 to 2.2 (p<0. 001), and mean sVNT levels increased from an inhibition of 17% to 96% (p<0.001). In a random subset of 20 participants, the geometric mean PRNT50 titers rose very substantially by at least 24 fold from Day 0 to Day 28 against the ancestral virus (p<0.001) and rose by at least 11 fold against the Omicron variant (p<0.001). In daily monitoring, post-vaccination reactions subsided within 7 days for over 99% of participants. ConclusionsA third dose of COVID-19 vaccination with an mRNA vaccine substantially improved antibody levels against the ancestral virus and the Omicron variant with well-tolerated safety profile, in adults who had received two doses of inactivated vaccine 6 months earlier. SummaryIn this open label trial of Chinese adults aged [≥]30 years who received two doses of inactivated COVID-19 vaccine 6 months earlier, third-dose mRNA vaccine substantially improved antibody levels against the ancestral virus and Omicron variant with well-tolerated safety profile.

Is greater than 145{degrees} of deep knee flexion under weight-bearing conditions safe after total knee arthroplasty?: a fluoroscopic analysis of Japanese-style deep knee flexion.

We investigated the characteristics of patients who achieved Japanese-style deep flexion (seiza-sitting) after total knee replacement (TKR) and measured three-dimensional positioning and the contact positions of the femoral and tibial components. Seiza-sitting was achieved after surgery by 23 patients (29 knees) of a series of 463 TKRs in 341 patients. Pre-operatively most of these patients were capable of seiza-sitting, had a lower body mass index and a favourable attitude towards the Japanese lifestyle (27 of 29 knees). According to two-/three-dimensional image registration analysis in the seiza-sitting position, flexion, varus and internal rotation angles of the tibial component relative to the femoral component had means of 148° (SD 8.0), 1.9° (SD 3.2) and 13.4° (SD 5.9), respectively. Femoral surface contact positions tended to be close to the posterior edge of the tibial polyethylene insert, particularly in the lateral compartment, but only 8.3% (two of 24) of knees showed femoral subluxation over the posterior edge. The mean contact positions of the femoral cam on the tibial post were located 7.8 mm (sd 1.5) proximal to the lowest point of the polyethylene surface and 5.5 mm (SD 0.9) medial to the centre of the post, indicating that the post-cam contact position translated medially during seiza-sitting, but not proximally. Collectively, the seiza-sitting position seems safe against component dislocation, but the risks of posterior edge loading and breakage of the tibial polyethylene post remain.

A double-blind comparative study of the safety and efficacy of caspofungin versus micafungin in the treatment of candidiasis and aspergillosis.

The safety and efficacy profile of caspofungin and micafungin in Japanese patients with fungal infections were directly compared in this prospective, randomized, double-blind study. The proportion of patients who developed significant drug-related adverse event(s) (defined as a serious drug-related adverse event or a drug-related adverse event leading to study therapy discontinuation) was compared in 120 patients [caspofungin 50 mg, or 50 mg following a 70-mg loading dose on Day 1 (hereinafter, 70/50 mg) group: 60 patients; micafungin 150 mg: 60 patients]. The overall response rate was primarily evaluated in the per-protocol set (PPS) population. The proportion of patients who developed significant drug-related adverse events was 5.0 % (3/60) in the caspofungin group and 10.0 % (6/60) in the micafungin group [95 % confidence interval (CI) for the difference: -15.9 %, 5.2 %]. The favorable overall response in the PPS population for patients with esophageal candidiasis, invasive candidiasis, and chronic pulmonary aspergillosis including aspergilloma was 100.0 % (6/6), 100.0 % (3/3), and 46.7 % (14/30) in the caspofungin group, and 83.3 % (5/6), 100.0 % (1/1), and 42.4 % (14/33) in the micafungin group, respectively. In Japanese patients with Candida or Aspergillus infections, there was no statistical difference in the safety between caspofungin and micafungin. Consistent with other data on these two agents, the efficacy of caspofungin and micafungin was similar.

Nationwide surveillance of bacterial respiratory pathogens conducted by the Japanese Society of Chemotherapy in 2007: general view of the pathogens' antibacterial susceptibility.

For the purpose of a nationwide surveillance of the antimicrobial susceptibility of bacterial respiratory pathogens in patients in Japan, the Japanese Society of Chemotherapy conducted their second year survey, during the period from January to August, 2007. A total of 1178 strains were collected from clinical specimens obtained from adult patients with well-diagnosed respiratory tract infections. Susceptibility testing was evaluable for 1108 strains (226 Staphylococcus aureus, 257 Streptococcus pneumoniae, 6 Streptococcus pyogenes, 206 Haemophilus influenzae, 120 Moraxella catarrhalis, 122 Klebsiella pneumoniae, and 171 Pseudomonas aeruginosa). A total of 44 antibacterial agents, including 26 beta-lactams (four penicillins, three penicillins in combination with beta-lactamase inhibitors, four oral cephems, eight parenteral cephems, one monobactam, five carbapenems, and one penem), three aminoglycosides, four macrolides (including ketolide), one lincosamide, one tetracycline, two glycopeptides, six fluoroquinolones, and one oxazolidinone were used for the study. Analysis was conducted at the central reference laboratory according to the method recommended by the Clinical and Laboratory Standards Institute (CLSI). The incidence of methicillinresistant Staphylococcus aureus (MRSA) was high, at 59.7%, and the incidences of penicillin-intermediateresistant and -resistant Streptococcus pneumoniae (PISP and PRSP) were 30.4% and 5.1%, respectively. Among Haemophilus influenzae strains, 19.9% of them were found to be beta-lactamase-non-producing ampicillin (ABPC)-intermediately-resistant (BLNAI), 29.1% to be beta-lactamasenon-producing ABPC-resistant (BLNAR), and 6.7% to be beta-lactamase-producing ABPC-resistant (BLPAR) strains. Extended-spectrum beta-lactamase-producing Klebsiella pneumoniae was not isolated. Two isolates (1.2%) of Pseudomonas aeruginosa were found to be metallo-beta-lactamase-producing strains, including one (0.6%) suspected multidrug-resistant strain showing resistance to imipenem, amikacin, and ciprofloxacin. These data will be a useful reference for future periodic surveillance studies and for investigations to control resistant infections as well. Continued surveillance is required to prevent the further spread of these antimicrobial resistances.

The first nationwide surveillance of bacterial respiratory pathogens conducted by the Japanese Society of Chemotherapy. Part 1: a general view of antibacterial susceptibility.

The Japanese Society of Chemotherapy (JSC) conducted the first nationwide surveillance of bacterial respiratory pathogens during the period from January to August 2006. With the cooperation of 32 medical institutions throughout Japan, a total of 924 strains belonging to seven clinically relevant bacterial species were collected from adult patients with well-diagnosed respiratory tract infections (RTIs). Antimicrobial susceptibility testing of the 887 evaluable strains (205 Staphylococcus aureus, 200 Streptococcus pneumoniae, 9 Streptococcus pyogenes, 165 Haemophilus influenzae, 91 Moraxella catarrhalis, 74 Klebsiella pneumoniae, and 143 Pseudomonas aeruginosa) to 42 antibacterial agents was conducted at the Central Laboratory of the Research Center for Anti-infective Drugs of the Kitasato Institute, according to recommendations issued by the Clinical and Laboratory Standards Institute (CLSI). The antibacterial agents employed were 25 beta-lactams, three aminoglycosides, four macrolides (including one azalide and one ketolide), one lincosamide, one tetracycline, two glycopeptides, five fluoroquinolones, and one oxazolidinone. The incidence of methicillin-resistant S. aureus (MRSA) was 63.4%, and the incidences of penicillin-intermediately resistant S. pneumoniae (PISP) and penicillin-resistant S. pneumoniae (PRSP) were 35.0% and 4.0%, respectively. Among H. influenzae, 21.2% of the strains were found to be beta-lactamase-nonproducing ampicillin (ABPC)-intermediately resistant (BLNAI), 29.1% to be beta-lactamase-nonproducing ABPC-resistant (BLNAR), and 4.8% to be beta-lactamaseproducing ABPC-resistant (BLPAR) strains. The incidence of extended-spectrum beta-lactamase-producing K. pneumoniae was 2.7% (2 of 74 strains). Three (2.1%) of the 143 P. aeruginosa strains were found to be metallo-beta-lactamaseproducing, including 1 (0.7%) multidrug-resistant strain. Through the nationwide surveillance, we obtained fundamental antimicrobial susceptibility data of clinically relevant bacterial pathogens in adult RTI to various antibacterial agents. These data will be a useful reference for future periodic surveillance studies, as well as for investigations to control antimicrobial-resistant pathogens.

Linezolid versus vancomycin for the treatment of infections caused by methicillin-resistant Staphylococcus aureus in Japan.

OBJECTIVES: To compare the efficacy and safety of linezolid and vancomycin for the treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections in Japan. METHODS: Patients with nosocomial pneumonia, complicated skin and soft-tissue infections or sepsis caused by MRSA were randomized to receive linezolid (600 mg every 12 h) or vancomycin (1 g every 12 h). RESULTS: One hundred patients received linezolid and 51 received vancomycin with outcomes evaluated at the end of therapy (EOT) and at the follow-up (FU), 7-14 days later. At EOT, clinical success rates in the MRSA microbiologically evaluable population were 62.9% and 50.0% for the linezolid and vancomycin groups, respectively; and microbiological eradication rates were 79.0% and 30.0% in the two groups, respectively (P < 0.0001). At FU, the clinical success rates were 36.7% for both groups and the microbiological eradication rates were 46.8% and 36.7%, respectively. Reversible anaemia (13%) and thrombocytopenia (19%) were reported more frequently in linezolid patients; laboratory analysis showed mild decrease in platelet counts with full recovery by FU. The mean platelet count in linezolid patients with thrombocytopenia was 101,000/mm(3). Significantly low platelet counts (<50,000/mm(3)) were observed more frequently in patients receiving vancomycin than in linezolid patients (6% versus 3%). Mean changes in haemoglobin levels between the two groups were not different. CONCLUSIONS: Linezolid is as effective as vancomycin for the treatment of MRSA infections and may be more effective than vancomycin in achieving microbiological eradication. Haematological adverse events were reported more frequently in linezolid-treated patients; analysis of laboratory data showed a mild reversible trend towards lower platelet counts.

Seroepidemiology of Chlamydia pneumoniae in Japan between 1991 and 2000.

AIM: To clarify the endemic and epidemic status of Chlamydia pneumoniae in Japan, the incidence of anti-C pneumoniae antibody was evaluated over a period of 10 years. METHOD: Serum samples were collected from 4756 healthy individuals aged 6 months to 88 years (2488 male and 2268 female individuals) between 1991 and 2000. The antibody titre was determined by a microimmunofluorescence test. RESULTS: After stratification by age and sex in each year, distinct peaks with prevalences of 73.3% and 73.0% were noted in 1993 and 1999, respectively. The lowest prevalence rate was seen in 1996 (59.0%). The epidemic cycle has been estimated to be almost six years in this geographical area. CONCLUSIONS: Chlamydia pneumoniae infection is highly endemic in Japan, as it is in Western countries, and there is a year to year variability. Long term studies in Japan are needed to clarify the epidemic occurrence of C pneumoniae infection.

[A discrepancy in the values of serum (1-3)-beta-D-glucan measured by two kits using different methods].

The measurement of serum (1-3)-beta-D-glucan (beta-glucan) in cases with deep seated mycosis is a useful diagnostic method. Beta-glucan has usually been measured using two different methods: by an alkali treatment, chromogenic automated kinetic assay (chromogenic assay), and by detergent dilution and heating methods, kinetic turbidimetric assay (turbidimetric assay). However, there are often large discrepancies in the beta-glucan values measured by these two methods. In this study, we reexamined the values of beta-glucan obtained by the two techniques, using 343 serum samples from 146 patients who had been treated in Kawasaki Medical School between January 1999 and May 1999, and then analyzed the reasons for the differences. Serum beta-glucan results measured were evaluated by segregating them into three clinical categories: cases with proven deep mycosis, cases with probable deep mycosis and cases without deep mycosis. In addition, the beta-glucan in the samples was suppressed by carboxy-methylated curdlan (CM-curdlan), and then was remeasured to find a non-specific reaction. Although a certain correlation was found between the serum beta-glucan results measured by the two methods, the values measured by the chromogenic assay were, in general, higher than those measured by the turbidimetric assay. There were also many samples in the cases without deep mycosis that showed positive values with the chromogenic assay, but not with the turbidimetric assay. With the turbidimetric assay, the addition of CM-curdlan suppressed the values of beta-glucan in all samples; however, when measured by the chromogenic assay the values in many samples remained high. These results suggest that a non-specific reaction which did not include beta-glucan was detected by the chromogenic assay. Further studies are needed to evaluate the characteristics and comparable usefulness of the two assays.

In vitro and in vivo activities of sitafloxacin against Chlamydia spp.

The in vitro and in vivo antichlamydial activity of sitafloxacin was investigated. The MICs and minimal chlamydiacidal concentrations of sitafloxacin for various species of chlamydia ranged from 0.031 to 0.125 microg/ml. Sitafloxacin had an excellent therapeutic effect on experimental Chlamydia psittaci pneumonia and was more potent than tosufloxacin, ofloxacin, and ciproflxacin, although slightly less potent than sparfloxacin.

[A case of Coxiella burnetii pneumonia in an adult].

A 49-year-old man visited our hospital complaining of a continuous high-grade fever and cough which had appeared during his stay in Indonesia. He was admitted on the same day because his laboratory data showed marked inflammatory changes and his chest radiograph revealed an infiltrative shadow in the right upper lung field. Initial treatment with beta-lactams was not effective and both his symptoms and his chest radiograph worsened. However, treatment with erythromycin clearly had an effect. Then, we carried out several tests for detection of atypical pathogens including Mycoplasma and Chlamydia. Finally, the case was diagnosed as one of Coxiella burnetii pneumonia because the DNA of C. burnetii was detected from his sera and seroconversion of C. burnetii--specific antibody was observed among paired serum samples. C. burnetii is one of the most commonly recognized pathogens among community-acquired pneumonias in Western countries, but in Japan, reports of community-acquired C. burnetii pneumonia have been rare. This difference may be due to the features of Q fever, in which there are large differences in frequency and form from country to country and among areas of the same country. Surveillance of C. burnetii pneumonia in Japan and different area will be required.

In vitro activity of telithromycin, a new ketolide, against Chlamydia pneumoniae.

The in vitro activity of telithromycin, a new ketolide, was compared with those of roxithromycin, azithromycin, clarithromycin and erythromycin A against 20 strains of Chlamydia pneumoniae. The MICs and minimal chlamydiacidal concentrations of telithromycin for the 20 C. pneumoniae strains both ranged between 0.031 and 0.25 mg/L. Telithromycin was twice as active as roxithromycin, azithromycin and erythromycin A, but less active than clarithromycin. These results appear to indicate that telithromycin is an effective antibiotic that should play some role in the treatment of respiratory tract infections caused by C. pneumoniae.

[Susceptibilities of bacteria isolated from patients with lower respiratory infectious diseases to antibiotics (1999)].

From October 1999 to September 2000, we collected the specimen from 430 patients with lower respiratory tract infections in 17 institutions in Japan, and investigated the susceptibilities of isolated bacteria to various antibacterial agents and antibiotics and patients' characteristics. Of 515 strains that were isolated from specimen (mainly from sputum) and assumed to be bacteria causing in inflammation, 506 strains were investigated. The breakdown of the isolated bacteria were: Staphylococcus aureus 78, Streptococcus pneumoniae 101, Haemophilus influenzae 104, Pseudomonas aeruginosa (non-mucoid) 58, P. aeruginosa (mucoid) 11, Moraxella subgenus Branhamella catarrhalis 41, Klebsiella pneumoniae 18, etc. Of 78 S. aureus strains, those with 4 micrograms/ml or above of MIC of oxacillin (methicillin-resistant S. aureus: MRSA) occupied 57.7%. Vancomycin and arbekacin showed the most potent activities against MRSA without detection of ABK-resistant strain (MIC: 64 micrograms/ml) and decrease of VCM-sensitive strains those were found in 1998. The frequency of S. pneumoniae exhibiting low sensitivity to penicillin (penicillin-intermediate S. pneumoniae: PISP + penicillin-resistant S. pneumoniae: PRSP) decreased to 34.7% from 46.0% in 1998. The frequency of PRSP was 3.0%, being the least number after 1991. Carbapenems showed strong activities against S. pneumoniae. Especially, panipenem inhibited the growth of all 101 strains with MIC of 0.063 microgram/ml. Generally, all drugs showed strong activities against H. influenzae with MIC80s of 4 micrograms/ml or below. MICs of ofloxacin ranged between 0.063 microgram/ml and 4 micrograms/ml in 1998, however, those were 0.125 microgram/ml or below in all H. influenzae in 1999 showing the strongest activity. Tobramycin and ciprofloxacin showed strong activities against P. aeruginosa (both mucoid and non-mucoid) with MIC80s of 1 microgram/ml. Number of isolated P. aeruginosa (mucoid) was little as 11, however, the susceptibilities to all drugs were better than P. aeruginosa (non-mucoid). K. pneumoniae showed good susceptibilities to all drugs except for ampicillin with decreasing of low-sensitive strains compared to those detected in 1998. Also, all drugs generally showed strong activities against M. (B.) catarrhalis. MIC80s of all drugs were 2 micrograms/ml or below. The drug which showed the strongest activity was imipenem inhibiting all 41 strains with MIC of 0.063 microgram/ml. On the patients' characteristics, the number of patients aged 80 years or older who had been increased was decreased in 1999 in the distribution by age. The percentage of the elderly patients aged 70 years or older was 47.0%, which occupied almost a half number of the total patients as in the last year. As for the incidence by disease, bacterial pneumonia and chronic bronchitis were the highest. They were noted in 37.9% and 30.5% of the patients, respectively. In 1999, bronchial asthma was frequently observed as compared in recent years. It was noted in about 10% of the patients which is the same % as in bronchiectasis. We examined the number of strains from these patients with infections before and after administration of antibiotics. In patients with bacterial pneumonia, the number of isolated strains was almost the same between those before and after administration. However, in patients with chronic bronchitis, the number of strains remarkably decreased to less than the half of the total after administration of antibiotics in the last year, but it decreased to 2/3 of the total in 1999. On the administration of antibiotics and isolated bacteria by the day of administration, the bacteria which were isolated more before administration were H. influenzae in 28.4%, S. pneumoniae in 25.7%, M. (B.) catarrhalis in 12.0% and S. aureus in 10.6%. The frequency of S. aureus after administration over 15 days was almost the same as that before administration, but the frequency of P. aeruginosa (both mucoid and non-mucoid) was 36.8% which was higher than that before administration. The frequency of isolated S. pneumoniae was decreased after administration and none of them was isolated after completion of administration. However, that of H. influenzae was decreased to 7.1% after administration within 3 days, and many H. influenzae were isolated after completion of administration as 21.4%.

[Outbreak of measles in a hospital and measures taken against hospital infection--evidence of cost and benefits].

In Japan, an isolated vaccine of measles is used because MMR vaccines have been suspended due to the frequent occurrence of aseptic meningitis after their use. It is administered only once with the cover rate having been approximately 70%. An outbreak of measles was experienced in eight of our health care workers (three doctors, three nurses and two clerks of our hospital) and in seven of our medical students, accompanying local outbreaks. Their condition was severe enough to require admission to our school hospital. One of medical students developed encephalitis, but he has recovered completely. The social cost including medical cost per worker was approximately yen 500,000 (about $4,500). We measured antibodies against measles, rubella, chickenpox and mumps using the ELISA assay in 1048 health care workers less than 40 years of age and 99 medical students before their clinical practice two or three months after the outbreak. The cost including the measuring of antibodies and vaccination for these workers and students was approximately yen 2,800,000 and it will be yen 700,000 for new workers each year. The negative rates for workers were 1.2% for measles, 8.8% for rubella, 10.0% for mumps and 2.0% for chickenpox and those for the medical students were 1.0%, 22.0%, 9.0% and 5.0%, respectively. Of the workers, 9.6% who had more than the defined very high tiaer were thought to have subclinical reinfection because they were non-symptomatic. The rates were 1.2% for rubella, 0.5% for chickenpox and 0.0% for mumps for more than the defined high titers among the workers, suggesting a risk of outbreaks in the future. Therefore, the antibodies of health care workers and medical students should be measured at the hospital and the antibody-negative person should be vaccinated to prevent infection not only from their patients but also prevent other patients from becoming infected by contracted health care workers or students.

[Atelectasis of the right lower lobe in association with bronchiolitis obliterans organizing pneumonia].

A 58-year-old woman with underlying rheumatoid arthritis was admitted to the hospital because of a dry cough and the presence of an abnormal shadow in the right lower lung field. Consolidation and volume loss in the right lower lobe with air bronchogram were recognized on a chest tomogram. Bronchofiberscopic examination disclosed neither stenosis nor tumors in the large bronchi. Organizing pneumonia was recognized pathologically in transbronchial lung biopsy (TBLB) specimens. The volume of the right lower lobe decreased rapidly, and new infiltration shadows appeared in the right upper and middle lobes. Another bronchofiberscope examination revealed organizing pneumonia, and macrophage infiltrations were seen in the alveoli on histopathological examination of the TBLB specimens. The diagnosis of RA-associated BOOP was made on the basis of agreement of the expansion of the shadows on chest radiographs, the RA symptoms and the RA factor. The patient was treated with prednisolone, and the clinical course was satisfactory, with no recurrence. This case was of interest because BOOP inducing lobar cicatricial atelectasis is very rare.

Proper use of MR imaging in internal derangement of the knee (orthopedic surgeon's view).

MR imaging of the knee is a highly accurate examination in terms of the detection of meniscal tears and cruciate ligament ruptures among internal derangement of the knee. The overall accuracy in more than 2000 published cases reached nearly as high as 90% in meniscal tears, and 94% in anterior cruciate ligament (ACL) and 99% in posterior cruciate ligament (PCL) ruptures. Furthermore, the negative predictive value of the knee MR imaging, the number of true negative examination results divided by the numbers of true negative plus false-negative examination results, reaches almost 100% because of its very low false-negative rate. Therefore, from the orthopedic surgeon's point of view, even though the medical cost becomes a great concern, MR imaging has prime importance in the diagnosis of the internal derangement of the knee.

The 7.5-kb common plasmid is unrelated to the drug susceptibility of Chlamydia trachomatis.

Using a new plaque cloning technique, we obtained unique Chlamydia trachomatis strains, which were confirmed to be free of the 7.5-kb common plasmid and glycogen in inclusions. The inclusions in plasmid-free and glycogen-negative strains were characterized by a target-like bull's eye morphology that appeared with the formation of a central translucent area that began to be seen clearly at 30 h postinoculation. The clear zone was composed of gel materials originating from reticulate bodies (RBs) that were abnormally large in size and irregular in shape, although one could not differentiate the aberrant RBs from normal RBs at early stages of development. The in-vitro susceptibility of these strains to various chemotherapeutic antibiotics was tested by comparison with their parent strains possessing the common plasmid. No difference was detected for any of the antibiotics tested, indicating that the 7.5-kb common plasmid is unrelated to the drug susceptibility of C. trachomatis.