Meningoencephalitis due to penicillin-resistantStreptococcus pneumoniae

The case of a 68-year-old man suffering from pneumococcal meningoencephalitis is reported. Antibacterial susceptibility tests revealed a multiply resistant pneumococcal strain. High doses of cefotaxime were necessary to sterilize the cerebrospinal fluid despite the achievement of a satisfactory level of antibiotic in the cerebrospinal fluid with moderate dosage. In France, as well as in many countries, high doses of third-generation cephalosporins such as cefotaxime or ceftriaxone should be administered for the initial therapy of suspected pneumococcal meningitis.     

Nonimmunocompromised mouse model of penicillin-resistantStreptococcus pneumoniae pneumonia

Penicillin-resistant strains ofStreptococcus pneumoniae (PRSP) are a growing problem, both in Japan and elsewhere. To study therapeutic approaches to respiratory infection by these resistant bacteria, we identified two clinically isolated PRSP strains which exhibit strong virulence against nonimmunocompromised CBA/J mice. Most mice infected with these strains die of pneumonia within two weeks. In infections by one strain, survival rates were slightly improved by bacampicillin doses of 20 mg/kg/day for five days but not by lower doses. Survival rates following infection by the other strain were unaffected by bacampicillin at any dose tested. We believe that our animal model of PRSP pneumonia using these two strains can be useful for evaluating therapy of PRSP infections.     

Effects of fluoroquinolones on experimental pneumonia caused by penicillin-resistantStreptococcus pneumoniae in mice

The in vitro and in vivo activities of several fluoroquinolones, ampicillin and cefteram-pivoxil were investigated against penicillin-resistantStreptococcus pneumoniae (PRSP). The MIC₉₀s of sparfloxacin, levofloxacin, tosufloxacin, AM-1155, ampicillin, and cefteram-pivoxil for 13 PRSP strains were 0.78, 3.13, 0.39, 1.56, 3.13, and 3.13 μg/mL, respectively. An experimental fatal pneumonia was induced by intranasal inoculation of PRSP No. 65 in CBA/J mice. The fluoroquinolones were effective against the experimental pneumonia, but ampicillin and cefteram-pivoxil were not sufficiently effective. The oral 50% effective doses (ED₅₀) of sparfloxacin, levofloxacin, tosufloxacin, and AM-1155 on the experimental pneumonia were 6.09, 49.3, 5.07, and 8.59 mg/kg/dose, respectively, when treatment was initiated 3 hours after infection and were 30.0, >50, 17.7, and 45.9 mg/kg/dose, respectively, when treatment was initiated 24 hours after infection. These results suggest that some fluoroquinolones such as sparfloxacin, tosufloxacin and AM-1155 may be effective in the treatment of pneumonia due to PRSP in humans.     

新型冠状病毒肺炎流行期间非感染病区医院感染预防和控制

本文总结了在新型冠状病毒肺炎流行期间非感染病区医院感染的预防和控制措施。医院应从医护员工培训、物资保障、患者及家属健康宣教、消毒隔离措施的实施、加强医院感染质控督查、疫情期心理危机干预等方面进行流程化管理,护理人员认真落实各项医院感染防控措施,加强质控监督,积极预防医院感染。     

Pharmacodynamic evaluation of tosufloxacin against Streptococcus pneumoniae in an in vitro model simulating serum concentration

We compared the antibacterial effects and the emergence of resistance to tosufloxacin or levofloxacin for Streptococcus pneumoniae by simulating the serum concentration according to the Japanese clinical regimens using an in vitro pharmacokinetic-pharmacodynamic model. For quinolone-susceptible strain ATCC49619, tosufloxacin showed bactericidal activity, given that both the AUC_0–24h/MIC ratios at the dosage of 150 mg t.i.d. and 300 mg b.i.d. of tosufloxacin tosilate were 138 and 193, and the C_max/MIC ranges were 7.93–10.2 and 15.9–17.6, respectively, which were greater than those of levofloxacin (100 mg t.i.d. and 200 mg b.i.d.). The greater area above the killing curves (AAKCs) or shorter time to achieve 99.9% killing (99.9% KT) in both models of tosufloxacin than those of levofloxacin was related to their larger AUC_0–24h/MIC and C_max/MIC. Exposure of only 100 mg t.i.d. of levofloxacin led to outgrowth of the parC mutants, which were twofold less susceptible to levofloxacin than the parent strain. Neither of the tosufloxacin tosilate regimens resulted in isolation of resistant mutants of this strain. For the parC mutant strain D-3197, both the AUC_0–24h/MIC and C_max/MIC ratios of tosufloxacin were greater than those of levofloxacin, which resulted in comparable or better bactericidal activity as compared to those of levofloxacin. However, both fluoroquinolones and both regimens led to outgrowth of resistant mutants, which possessed a mutation in gyrA in addition to parC. In conclusion, tosufloxacin is superior to levofloxacin in bactericidal activity against S. pneumoniae in the Japanese clinical regimens, especially in the quinolone-susceptible strain, without emergence of resistant subpopulations.     

Prevalence of Chlamydophila pneumoniae among Bangladeshi children under age 5 years with acute respiratory infections

Despite major improvements in the diagnosis of pathogenic organisms causing acute respiratory infections (ARIs), details of infections caused by atypical pathogens are not well understood, particularly in developing countries. This clinical and epidemiological research was conducted in Bangladesh to explore the prevalence of atypical pathogens in causing childhood pneumonia. Sixty-four children with ARI were studied at the Pediatric Outpatient Department of Dhaka Medical College Hospital, Bangladesh, during September through December 2000. In addition to clinical examination, hematological, radiological, and bacteriological examinations were performed. Antibody titers from paired sera against Mycoplasma pneumoniae and Legionella spp. in the acute and convalescent phases revealed that none of these children were infected with M. pneumoniae, while only one serum sample was positive for L. pneumophila serogroup 4. Antibody titers against Chlamydophila (Chlamydia) pneumoniae, determined by an indirect microimmunofluorescence method, and by an enzyme-linked immunosorbent assay (ELISA) kit (HITAZYME C. pneumoniae kit) indicated that 13 children (20.3%) were infected with C. pneumoniae. Our results indicate a high prevalence rate of C. pneumoniae, suggesting it is as an important causative pathogen of childhood pneumonia in Bangladesh.     

Evaluation of the diagnostic usefulness of real-time PCR for detection of Chlamydophila pneumoniae in acute respiratory infections

We investigated whether a real-time polymerase chain reaction (PCR) test is a useful diagnostic tool for identifying individuals with acute respiratory Chlamydophila pneumoniae infections. Nasopharyngeal swab specimens and peripheral blood mononuclear cells (PBMCs) from 100 patients with acute respiratory tract infections and 140 asymptomatic healthy subjects (controls) were analyzed using real-time PCR, culture, and serology for the detection of C. pneumoniae. Six patients had serological results indicating acute C. pneumoniae infections. C. pneumoniae DNA was detected in respiratory samples from eight patients (three of these cases were serologically confirmed as having C. pneumoniae infections) and four controls. The amount of C. pneumoniae DNA present in the real-time PCR for the samples was calculated, and no significant differences in the amount of DNA between symptomatic and asymptomatic subjects were found. On the other hand, traces of C. pneumoniae DNA were detected in PBMCs from eight patients, but this was confirmed in PBMCs from only seven of these patients. Only one patient had both respiratory and blood samples that were positive. C. pneumoniae DNA was also detected in samples from six controls, but no significant differences in the amount of C. pneumoniae DNA were observed between patients and controls. The present quantitative real-time PCR assay does not seem to be a useful method for differentiating between C. pneumoniae acute infections and persistent ones or nasopharyngeal carriage. In addition, the detection of C. pneumoniae DNA in PBMCs does not seem to be a suitable method for the diagnosis of acute respiratory C. pneumoniae infections.     

Nontypeable Streptococcus pneumoniae as an otopathogen

Among 34 Streptococcus pneumoniae (Spn) sequential isolates from middle ear fluid, we found a case of a nontypeable S. pneumoniae (NT-Spn) in a child with acute otitis media (AOM). The strain was pneumolysin PCR positive and capsule gene PCR negative. Virulence of the NT-Spn was confirmed in a chinchilla model of AOM.     

The effect of inhaled corticosteroids on Chlamydophila pneumoniae and Mycoplasma pneumoniae infection in children with bronchial asthma

The purpose of this study was to clarify whether inhaled corticosteroids (ICSs) increased the infectious load of Chlamydophila pneumoniae and/or Mycoplasma pneumoniae in the respiratory tracts of asthmatic children. We studied a total of 310 outpatients with chronic stable asthma. Real-time polymerase chain reaction (PCR)-positive results for C. pneumoniae were obtained in 21 of 310 (6.8%) throat samples and 21 of 293 (7.2%) nasopharyngeal samples. There was no significant difference in the rate of detection or in the quantity of detection for C. pneumoniae between the ICS group and the non-ICS group, nor were there differences among groups classified by Japanese pediatric guidelines (JPGL) severity criteria. Real-time PCR-positive results for M. pneumoniae were obtained in 60 of 310 (19.4%) throat samples and 49 of 293 (16.7%) nasopharyngeal samples. There was no significant difference in the rate of detection or the quantity of detection between the ICS group and the non-ICS group, nor were there differences among age groups. The results of this research do not support the hypothesis that ICSs influence the infectious load of C. pneumoniae and M. pneumoniae. ICSs did not increase C. pneumoniae or M. pneumoniae infection in the upper respiratory tract, in contrast to the effect of ICSs in causing oral candidiasis. Our data exclude the concern that there is an increase in C. pneumoniae and M. pneumoniae infections due to ICS use, the use of ICSs being the gold standard in the long-term anti-inflammatory treatment of persistent asthma in children and adults.     

An outbreak of Pseudomonas aeruginosa infections following thoracic surgeries occurring via the contamination of bronchoscopes and an automatic endoscope reprocessor

An outbreak of Pseudomonas aeruginosa infections occurred after thoracic surgeries performed between May and June 2003. Clinical data of seven patients were reviewed and the fact was revealed that bronchoscopes were used during endotracheal intubation for one-lung ventilation in most patients. P. aeruginosa was recovered from the sputum of these patients at a very early stage post-operation. Environmental samples from bronchoscopes and an automated endoscope reprocessor (AER) were cultured and P. aeruginosa strains were recovered from all of them. All of these strains were confirmed to be identical by pulsed-field gel electrophoresis (PFGE). Inspection of the sterilization cycles of bronchoscopes revealed inappropriate management of bronchoscopes and a flaw in the AER; once its detergent tank was contaminated, it was not possible to disinfect it. After all the bronchoscopes had been disinfected, and the washing machine had been remodeled, with the washing process confirmed to be appropriate, the outbreak finally ended. This outbreak had two causes, a flaw in the AER and inappropriate disinfection procedures. Outbreaks associated with bronchoscopic examinations have been reported elsewhere. Bronchoscopes are widely used to facilitate endotracheal intubation, especially for one-lung anesthesia. Although they are used for only a short time during anesthetic procedures, we should handle them more carefully.     

Evaluation of the Binax NOW Streptococcus pneumoniae urinary antigen assay in intensive care patients hospitalized for pneumonia

Objective To evaluate the diagnostic performance of Binax Now S. pneumoniae urinary antigen rapid immunochromatographic membrane test (ICT) for patients with suspicion of community-acquired pneumonia hospitalized in intensive care and to assess the impact of prior antibiotics on its diagnostic performance.Design and setting Retrospective study in a medicosurgical ICU in a 700-bed general hospital.Patients Charts of patients with ICT performed (result blinded) were reviewed between May 2002 and July 2004. ICT has been performed in 140 of the 1,006 patients hospitalized in the unit; two-thirds had received antibiotics prior to admission.Measurements and results Diagnosis of pneumonia was made according to usual criteria. All patients had at least one microbiological test. Pneumonia diagnosis confirmed in 108 patients including 32 pneumococcal. ICT was positive in 23 of 32 patients with pneumococcal pneumonia, in 11 of 108 without, and in none of the 32 patients without pneumonia, resulting in sensitivity, specificity, and positive and negative predictive values of, respectively: 72%, 90%, 68% and 92%. Positive likelihood ratios were comparable among patients with or without prior antibiotics (respectively 6 and 12 for 7 in the overall population).Conclusions This first clinical evaluation of ICT in intensive care patients hospitalized for suspicion of community-acquired pneumonia, demonstrated performance in accordance with published data even in the case of prior antibiotics. Its clinical interest and impact on antibiotics policy remain to be refined.     

The characteristics of NDM-producing Klebsiella pneumoniae from Canada

After recent hospitalization in India (New Delhi and Mumbai), 2 patients, on their return to Canada, presented with lower urinary tract infections due to multiresistant Klebsiella pneumoniae that produced New Delhi metallo-β-lactamase and CTX-M-15. The organisms belonged to clones ST147 and ST340, and were positive for aac(6′)-Ib-cr, as well as for the ccdAB and vagCD addiction systems. The bla_NDM plasmid was located on the IncFIIA and IncA/C replicon groups of plasmids. Clones ST147 and ST340 are also responsible for harbouring bla_KPC, and it is possible that they played an important role in the intercontinental spread of antimicrobial resistance.     

In vitro and in vivo activities of sparfloxacin and reference drugs againstChlamydia pneumoniae

The activities of sparfloxacin and reference drugs againstChlamydia pneumoniae were compared by using in vitro and in vivo methods. The minimum inhibitory concentration (MIC) (μg/ml) ranges of sparfloxacin, levofloxacin, tosufloxacin, grepafloxacin, AM-1155, DU-6859a, clarithromycin, azithromycin, and minocycline for sixC. pneumoniae strains (two standard and four clinical strains) were 0.031 to 0.063, 0.25 to 0.5, 0.063 to 0.125, 0.063 to 0.125, 0.063 to 0.125, 0.031 to 0.063, 0.016 to 0.031, 0.125 to 0.25, and 0.016 to 0.031, respectively. The in vitro potency of sparfloxacin againstC. pneumoniae was similar to that of clarithromycin, minocycline, and DU-6859a, and higher than that of the other fluoroquinolones and azithromycin. Fatal pneumonia was induced in cyclophosphamide-treated leukopenic mice by intranasal inoculation withC. pneumoniae KKpn-2. Infiltration of the lung by neutrophils and lymphocytes was confirmed by histopathologic examination. Oral treatment with the various antichlamydial agents was given for seven days; sparfloxacin and minocycline had the lowest ED₅₀ (effective treatment dose in 50% of the mice; given as mg/kg per dose) (1.11 each), followed by DU-6859a (1.92), tosufloxacin (2.09), grepafloxacin (2.41), clarithromycin and azithromycin (2.48 each), AM-1155 (2.77), and levofloxacin (>10). These results suggest that sparfloxacin may be an effective agent forC. pneumoniae infection in humans.     

Bactericidal activity of 5 beta-lactam antibiotics againstStreptococcus pneumoniae

Assays were performed to determine bactericidal activity as a function of time (1, 3, 5, and 7 hours) and of the concentration (1, 2, 4, and 8 MIC) of antibiotics for 2 penicillin-sensitive strains ofStreptococcus pneumoniae (MIC<0.06 mg/L), 2 strains with moderate penicillin sensitivity (MIC=0.125 mg/L) and 2 penicillin-resistant strains (MIC-2 mg/L). The beta-lactam antibiotics studied were penicillin, amoxicillin, cefotaxime, imipenem and cefpirome. Imipenem was the antibiotic with the greatest antibacterial activity, followed by amoxicillin. The bactericidal activity of all the antibiotics was greater against the penicillin-sensitive strains than against those strains with some degree of resistance. However, the bactericidal activity observed for cefpirome suggests that further studies are necessary to determine the value of this antibiotic in the treatment of severeS. pneumoniae infections.     

Macrolide resistance of Streptococcus pneumoniae isolated during long-term macrolide therapy: difference between erythromycin and clarithromycin

Longterm macrolide therapy (LTMT) has been employed as an effective therapy both for diffuse panbronchiolitis in Japan and for cystic fibrosis in European countries. However, effects on antibiotic susceptibility profiles of microorganisms, associated with such long-term administration of antibiotics, are of concern. We retrospectively identified 57 pneumococcal isolates, recovered from the same number of patients receiving either LTMT with 400mg of clarithromycin daily (CAM group; n = 31) or 600mg of erythromycin daily (EM group; n = 26) by reviewing the patients records at Nara Medical University. On analysis, we found that all isolates recovered from the CAM group and 25 of the 26 recovered from the EM group were resistant to EM, showing either an MLSB or an M phenotype. Interestingly, isolates exhibiting the M phenotype were much less frequent in the CAM group (2 of 31; 6.5%) than in the EM group (15 of 26; 57.7%). No increase in the rate of penicillin resistance was observed in either group. The macrolide resistance profiles of microorganisms may be influenced differently according to differences in the kind of macrolide antibiotics used.     

Optimized serodiagnosis of Mycoplasma pneumoniae infections

Serologic methods are well established for the diagnosis of Mycoplasma pneumoniae infections in humans, but they are less sensitive than polymerase chain reaction (PCR). To improve their sensitivity, a new panel of antigens was tested. Compared with PCR results, up to 92% of PCR-positive patients were confirmed by our immunoblotting approach having a specificity between 92.6% and 100%.     

Serotype distribution and antimicrobial resistance patterns of Streptococcus pneumoniae isolated from children in China younger than 5 years

This study examined the epidemiology, antibiotic susceptibility, and serotype distribution of Streptococcus pneumoniae associated with invasive and noninvasive pneumococcal disease in children in China. A total of 451 clinical isolates from children (age, <5 years) were collected from 8 cities from January 2005 to December 2006, including 31 isolated from invasive disease. In vitro susceptibility to 14 antimicrobial agents was determined by the agar dilution method. Among all isolates tested, 64.3% were resistant to penicillin, and for invasive isolates, the resistance rate was 55.2%. Isolates from Wuhan and Nanjing showed the highest prevalence of penicillin resistance (89.6% and 85%), followed by those from Shenzhen (72.4%) and Chengdu (56.7%). Multidrug resistance rates to tetracycline, erythromycin, and clindamycin reached 90%. The 6 most common serotypes were 19F, 19A, 14, 6B, 23F, and 15. These accounted for 80.7% of the isolates. Resistance to penicillin varied among the 6 leading serotypes, ranging from 20% in serotype 15 to 87.3% in serotype 19F. Each of the 8 cities had different serotype distribution. The potential coverage by 7-, 10-, and 13-valent pneumococcal conjugate vaccine were 63.6%, 64.8%, and 79.6%, respectively.     

A specific polymerase chain reaction test for the identification of Streptococcus pneumoniae

Using an approach based on the comparison of arbitrary primer polymerase chain reaction (PCR) genomic profiles from oral streptococci and Streptococcus pneumoniae strains, we identified a 434-bp genomic fragment apparently specific for S. pneumoniae. From the nucleotidic sequence of this common fragment, a pair of primers was designed and tested on a set of strains comprising the major Streptococcus species. One species, S. anginosus, gave an amplification product of the same length as S. pneumoniae. Sequence comparison of the S. anginosus and S. pneumoniae amplicons revealed several variations which were used to define a new set of primers giving a 181-bp S. pneumoniae-specific fragment. The amplified fragment contains the 5' terminal part of a gene encoding a putative sugar-specific permease and an intergenic sequence. The PCR test was evaluated on 257 strains of invasive S. pneumoniae corresponding to clinical isolates and on 153 non-pneumoniae oral streptococci strains; in addition, 3 S. pseudopneumoniae strains were tested. With these primers, an amplification product was only obtained with the S. pneumoniae strains. Moreover, the test was successfully evaluated on 10 atypical S. pneumoniae strains related to pneumococcal diseases. In this study, we therefore established the capacity of a simple PCR test to discriminate S. pneumoniae from other Streptococci (including S. pseudopneumoniae), thus allowing rapid and accurate diagnosis.     

Pharmacokinetics-pharmacodynamics of quinolones against Streptococcus pneumoniae in patients with community-acquired pneumonia

Exposure-response analyses were performed using data from 89 patients (10 clinical trials) with Streptococcus pneumoniae community-acquired pneumonia who received quinolones. Relationships between the free-drug AUC/MIC ratio and clinical and microbiologic response were identified. Such data may be useful to establish prior expectations for the no-treatment effect when conducting noninferiority clinical trials.