Causative bacteria of respiratory tract infections in Kuwait by quantitative culture of sputum

To determine the bacterial etiology of lower respiratory tract infections in Kuwait, we performed quantitative culture of sputum and measured the susceptibilities of the isolated bacteria against different antibiotics. A total of 140 sputum samples were collected for a period of 14 months for the study. Single and multiple pathogens as a cause of infection were isolated from 55 and 15 samples, respectively. A total of 53.8% of Streptococcus pneumoniae were penicillin-resistant and 52% and 57% of Hemophilus influenzae and Moraxella catarrhalis were β-lactamase positive, respectively. We concluded that the major pathogens of respiratory tract infections in Kuwait were H. influenzae, M. catarrhalis, S. pneumoniae, and Pseudomonas aeruginosa, and there was an increased resistance among the isolated bacteria against commonly used antibiotics. Received: April 2, 1999 / Accepted: June 23, 1999     

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 β-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 β-lactamase-nonproducing ampicillin (ABPC)-intermediately resistant (BLNAI), 29.1% to be β-lactamase-nonproducing ABPC-resistant (BLNAR), and 4.8% to be β-lactamaseproducing ABPC-resistant (BLPAR) strains. The incidence of extended-spectrum β-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-β-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.     

Antibiotic susceptibility in aerobic gram-negative bacilli isolated in intensive care units in 39 French teaching hospitals (ICU study)

Objective Evaluation of the distribution and antibiotic susceptibility of the aerobic gramnegative bacilli (AGNB) isolated from patients in intensive care units (ICU study).Design and setting Microbiological study carried out in 1991 in 39 teaching hospitals. A standardized method was used to determine the minimum inhibitory concentrations of 12 antibiotics against 3366 strains of AGNB (close to 100 strains per hospital) during a period of 3 months.Results The 2773 initial strains (i.e., the first AGNB isolate for a given species and a given patient) were mainly isolated from the respiratory tract (34.4%), urinary tract (23%), or blood (9.6%) and were mainlyPseudomonas aeruginosa (22.9%),Escherichia coli (22%), Acinetobacter (9.7%), andKlebsiella pneumoniae (8.3%).E. coli was prominent in urine and blood andP. aeruginosa in the respiratory tract. Overall, the rate of susceptibility of AGNB was 58 to 65% to piperacillin, cefotaxime, and gentamicin; 69 to 75% to aztreonam, tobramycin, and ciprofloxacin; 83% to ceftazidime; and 91% to imipenem. The overall rates of susceptibility were higher for the initial strains isolated from blood than for those from the urinary or respiratory tracts, mostly reflecting differences in species distribution. Susceptibility rates were lower for the 593 repeat strains (i.e., all the subsequent isolates for a given species and a given patient) than for the initial strains, mostly due to the higher proportion of resistant species (P. aeruginosa 45.9%) but also due to the difference in susceptibility rates for some species-antibiotic combinations. Concomitant resistance (i.e., resistance to several antibiotics due to independent mechanisms of resistance) was marked between -lactams and aminoglycosides or quinolones, particularly inP. aeruginosa andK. pneumoniae.Conclusions Rates of resistance in AGNB as a whole and in particular species (P. aeruginosa, Klebsiella), as well as frequency of concomitant resistance found in the French ICU study, were higher than those found in ICU studies conducted with the same methodology in Belgium, The Netherlands, and Germany, which may reflect differences in case mix.     

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 β-lactams (four penicillins, three penicillins in combination with β-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 β-lactamase-non-producing ampicillin (ABPC)-intermediately-resistant (BLNAI), 29.1% to be β-lactamasenon-producing ABPC-resistant (BLNAR), and 6.7% to be β-lactamase-producing ABPC-resistant (BLPAR) strains. Extended-spectrum β-lactamase-producing Klebsiella pneumoniae was not isolated. Two isolates (1.2%) of Pseudomonas aeruginosa were found to be metallo-β-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.     

Nationwide surveillance of bacterial respiratory pathogens conducted by the surveillance committee of the Japanese Society of Chemotherapy,the Japanese Association for Infectious Diseases,and the Japanese Society for Clinical Microbiology in 2019–2020: General view of the pathogens' antibacterial susceptibility

The trends and prevalence of antimicrobial susceptibility of pathogens vary by country, region, and time. Long-term regular surveillance is required to investigate trends in the antimicrobial resistance of various isolated bacterial pathogens. We report the results of a nationwide surveillance on the antimicrobial susceptibility of bacterial respiratory pathogens in Japan conducted by the Japanese Society of Chemotherapy, the Japanese Association for Infectious Diseases, and the Japanese Society for Clinical Microbiology. The isolates were collected from clinical specimens obtained from adult patients who visited a collaborating medical facility between June 2019 and December 2020 and were diagnosed with respiratory tract infections by a physician. Antimicrobial susceptibility testing was performed in a centralized laboratory according to the methods recommended by the Clinical and Laboratory Standards Institute.Susceptibility testing was performed for 932 strains (201 Staphylococcus aureus, 158 Streptococcus pneumoniae, 6 S. pyogenes, 136 Haemophilus influenzae, 127 Moraxella catarrhalis, 141 Klebsiella pneumoniae, and 163 Pseudomonas aeruginosa) collected from 32 facilities in Japan. The proportions of methicillin-resistant S. aureus and penicillin-resistant S. pneumoniae were 35.3% and 0%, respectively. In H. influenzae, 16.2% and 16.9% were β-lactamase-producing ampicillin resistant and β-lactamase-negative ampicillin resistant, respectively. Extended-spectrum β-lactamase-producing K. pneumoniae accounted for 5.0% of all K. pneumoniae infections. Carbapenemase-producing K. pneumoniae and multi-drug-resistant P. aeruginosa with metallo-β-lactamase were not detected in this study. This surveillance will be a useful reference for treating respiratory infections in Japan and will provide evidence to enhance the appropriate use of antimicrobial agents.     

Comparative in vitro activity of carbapenem antibiotics against respiratory pathogens isolated in recent years

We investigated the antibacterial activity of 12 antibiotics, including 4 carbapenems, against 200 strains of respiratory pathogens isolated in 1997, and compared the results with those obtained in 1993. The strains examined were 38 strains of methicillin-susceptible Staphylococcus aureus (MSSA), 32 strains of methicillin-resistant S. aureus (MRSA), 22 strains of penicillin-susceptible Streptococcus pneumoniae (PSSP), 10 strains of penicillin-resistant S. pneumoniae (PRSP), 53 strains of Pseudomonas aeruginosa, 19 strains of Moraxella catarrhalis, and 26 strains of Haemophilus influenzae. In 1993, 100 strains were examined. The minimal inhibitory concentration data of the present study showed that imipenem and panipenem were more active than the other agents against gram-positive bacteria, and that meropenem and biapenem were more active than the other agents against gram-negative bacteria. By comparing these results with those obtained in 1993, it was found that increase of resistance to carbapenem antibiotics was not observed against all the strains tested in this study. Thus, it can be stated that carbapenem antibiotics retain their position as the drug of first choice for severe infections. Received: January 4, 1999 / Accepted: May 26, 1999     

Nationwide surveillance of bacterial respiratory pathogens conducted by the surveillance committee of japanese society of chemotherapy,the japanese association for infectious diseases,and the japanese society for clinical microbiology in 2016: General view of the pathogens’ antibacterial susceptibility

The nationwide surveillance on antimicrobial susceptibility of bacterial respiratory pathogens from the patients in Japan was conducted by the Japanese Society of Chemotherapy, the Japanese Association for Infectious Diseases, and the Japanese Society for Clinical Microbiology in 2016.The isolates were collected from clinical specimens obtained from well-diagnosed adult patients with respiratory tract infections during the period between February 2016 and August 2016 by three societies. Antimicrobial susceptibility testing was conducted at the central reference laboratory according to the method recommended by Clinical Laboratory Standards Institute.Susceptibility testing was evaluated in 1062 strains (143 Staphylococcus aureus, 210 Streptococcus pneumoniae, 17 Streptococcus pyogenes, 248 Haemophilus influenzae, 151 Moraxella catarrhalis, 134 Klebsiella pneumoniae, and 159 Pseudomonas aeruginosa). Ratio of methicillin-resistant S. aureus was 48.3%, and those of penicillin-susceptible S. pneumoniae was 99.5%. Among H. influenzae, 14.1% of them were found to be β-lactamase-producing ampicillin-resistant strains, and 41.1% to be β-lactamase-non-producing ampicillin-resistant strains. Extended spectrum β-lactamase-producing K. pneumoniae and multi-drug resistant P. aeruginosa with metallo β-lactamase were 4.5% and 0.6%, respectively.     

In vitro antimicrobial activity and penetration rate into sputum of gatifloxacin, a novel 6-fluoro-8-methoxy quinolone, and its therapeutic efficacy in respiratory infections

The in vitro antimicrobial activity of gatifloxacin against clinical isolates of pathogenic bacteria was evaluated. Minimum inhibitory concentrations of gatifloxacin, ofloxacin, ciprofloxacin, tosufloxacin, sparfloxacin, and rifampicin against 20 strains each of methicillin-susceptible Staphylococcus aureus, methicillin-resistant Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Serratia marcescens, and Pseudomonas aeruginosa, 18 strains of Enterobacter cloacae, 15 strains each of Streptococcus Pneumoniae and Moraxella catarrhalis, 12 strains of Haemophilus influenzae, 18 strains of Mycobacterium intracellulare, and 22 strains each of Mycobacterium tuberculosis and Mycobacterium avium were determined. The minimum inhibitory concentrations₉₀'s of gatifloxacin against the above species were 0.12, 8, ≦0.06, 0.5, 2, 2, ≦0.06, 0.39, 0.05, 0.013, 2, 0.5, and 4 μg/ml, respectively. Gatifloxacin was four times as active as ofloxacin against methicillin-susceptible and -resistant Staphylococcus aureus, and as active as ofloxacin against Enterobacteriaceae and Pseudomonas aeruginosa. Gatifloxacin was as active as tosufloxacin and sparfloxacin against Streptococcus pneumoniae, Moraxella catarrhalis, and Haemophilus influenzae. The antimycobacterial activity of gatifloxacin was similar to that of sparfloxacin. Five patients with chronic respiratory infections and one patient with acute pneumonia received 100–400 mg/day of gatifloxacin orally for 5–12 days (mean, 8.17 days). The clinical effects were excellent in one patient and good in five. One strain of Haemophilus influenzae was eradicated and one strain of Pseudomonas aeruginosa persisted after therapy. Adverse reactions were mild and improved after completion of therapy. In one patient with chronic bronchitis, the maximum sputum concentrations 2–4 h after oral administration of 150 mg of gatifloxacin on days 1 and 6 were 0.88 and 1.45 μg/ml, respectively, and in serum the values were 0.84 and 1.24 μg/ml, respectively. Thus it was found that gatifloxacin possesses potent activity against respiratory pathogens (including Mycobacteriaceae), and shows good penetration rate into sputum, and that it can be used as the drug of first choice in the treatment of respiratory tract infections. Received: October 6, 1998 / Accepted: February 23, 1999     

Antibacterial activity of tosufloxacin against major organisms detected from patients with respiratory or otorhinological infections: comparison with the results obtained from organisms isolated about 10 years ago

The minimum inhibitory concentrations (MICs) of tosufloxacin and other fluoroquinolone antimicrobials for Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella (Branhamella) catarrhalis, isolated, between January 2003 and July 2004, from patients suspected of having respiratory or otorhinological infections were determined. The results were compared with those for these organisms isolated in 1994, plus some H. influenzae strains isolated in 1998. Tosufloxacin was the most potent of all the antibiotics tested for antibacterial activity against S. pneumoniae (including penicillin-intermediate S. pneumoniae and penicillin-resistant S. pneumoniae). The MIC₅₀ and MIC₉₀ values did not differ from those obtained for the strains isolated in 1994. Fluoroquinolones exerted the most potent antibacterial activity against M. (B.) catarrhalis; the MICs for most of the strains were ≦0.06 μg/ml; fluoroquinolones inhibited the growth of all the strains at 0.25 μg/ml or less. Fluoroquinolones showed the most potent antibacterial activity against H. influenzae strains isolated between 2003 and 2004, and in 1994, but, for one H. influenzae strain isolated, between 2003 and 2004, the MICs of fluoroquinolones were high. Some strains of S. pneumoniae and H. influenzae were resistant to fluoroquinolones. Genetic analysis showed that all of these strains had mutations in the quinolone resistance-determining region, but there were no differences according to the years of isolation. These results indicate that tosufloxacin has potent antibacterial activity against major organisms isolated from patients with respiratory or otorhinological infections; further, the results of the present study did not differ from those obtained about 10 years ago.     

Population pharmacokinetics and pharmacodynamics of cefpirome in critically ill patients against Gram-negative bacteria

Objectives To develop a population pharmacokinetics model for cefpirome in ICU patients, to assess pharmacokinetic-pharmacodynamic profiles vs. MIC distribution of likely ICU pathogens, and to assess their expected cumulative fraction of response (CFR). Design and setting Prospective observational study in a multidisciplinary ICU. Measurements and results Twelve patients received 2 g cefpirome intravenously over 12 h. Thirteen blood samples were taken on two occasions. Demographic and creatinine clearance data were collected. Based on the final covariate model obtained using NONMEM, Monte Carlo simulations were undertaken to simulate free-drug concentrations for two administration methods: intermittent bolus administration (IBA) and continuous infusion (CI) with a loading dose of 0.5 g. Concentration-time profiles were evaluated by the probability of achieving free-drug concentrations above the MIC for more than 65% of dosing interval. Using MIC distributions from the EUCAST programme the CFR for each method was evaluated. A three-compartment model with zero-order input best described the concentration-time data. The CFR for Escherichia coli and Klebsiella spp. was greater than 97% in all IBA and CI doses but for Pseudomonas aeruginosa, and Acinetobacter spp. achieved target concentrations of 56% and 46%, respectively. High-dose CI cefpirome (6 g/day) for P. aeruginosa and Acinetobacter spp. was required to achieve CFR of 89%. Conclusion Measured creatinine clearance appears to be a good marker of cefpirome clearance and potentially could be used to individualise cefpirome therapy. When given as IBA or CI for E. coli and Klebsiella spp., cefpirome should be successful. Cefpirome fails to achieve the bactericidal target even when administered at high-doses such as 6 g/day for P. aeruginosa and Acinetobacter spp. Prospective clinical studies are needed to conclusively validate these findings.     

Comparative in-vitro activity of carbapenem antibiotics against respiratory pathogens isolated between 1999 and 2000

We investigated the antibacterial activity of 12 antibiotics, inclusive of four carbapenems, against 167 strains of respiratory pathogens isolated between 1999 and 2000. Thirty strains of methicillin-susceptible Staphylococcus aureus (MSSA), 28 strains of methicillin-resistant S. aureus (MRSA), 11 strains of penicillin-susceptible Streptococcus pneumoniae (PSSP), 29 strains of penicillin-resistant S. pneumoniae (PRSP), 30 strains of Pseudomonas aeruginosa, 14 strains of Moraxella catarrhalis, and 25 strains of Haemophilus influenzae were examined. The minimum inhibitory concentration (MICs)_50/90 (μg/ml) of imipenem, panipenem, meropenem, and biapenem against the clinical isolates obtained between 1999 and 2000 were: 0.06/0.25, 0.12/0.25, 0.12/0.25, and 0.12/0.25, respectively, against MSSA; 16/32, 16/32, 16/32, and 8/32 against MRSA; ≦0.015/0.06, ≦0.015/0.03, 0.03/0.12, and ≦0.015/0.06 against PSSP; 0.12/0.25, 0.03/0.06, 0.25/0.5, and 0.12/0.25 against PRSP; 1/8, 2/8, 0.5/2, and 2/16 against P. aeruginosa; 0.06/0.06, 0.03/0.06, ≦0.015/0.06, and 0.06/0.12 against M. catarrhalis; and 1/4, 1/4, 0.12/0.25, and 2/4 against H. influenzae. A comparison of the antibacterial activity of the four carbapenems with that found in our previous studies showed no significant difference in the susceptibility of clinical isolates, except for a slight decrease in the susceptibility of MSSA. Carbapenems have remained effective for severe infections. The MIC data showed that imipenem and panipenem were more active than meropenem and biapenem against gram-positive bacteria, and that meropenem and biapenem were more active than imipenem and panipenem against gram-negative bacteria. As only meropenem had an MIC₉₀ below the breakpoint of pneumonia against all species except MRSA, meropenem was considered to be the most potent of the four carbapenems studied. Received: February 8, 2001 / Accepted : June 5, 2001     

Antimicrobial susceptibility of pathogens isolated from more than 10 000 patients with infectious respiratory diseases: a 25-year longitudinal study

The Study Group on Antimicrobial Susceptibility of Pathogens Isolated from Respiratory Infections was established in 1981 in Japan to elucidate trends in such susceptibilities in patients with infectious respiratory diseases; the Group has conducted nationwide research in collaboration with 21 medical institutions. Examination of more than 10 000 patients by 2005 allowed a summary of study findings. Streptococcus pneumoniae started to become resistant to penicillin G in the 1990s, and the isolation rate of penicillin-intermediate and penicillin-resistant S. pneumoniae (PISP + PRSP) reached almost 60% in 2001. The proportion of PRSP also increased, reaching 19.4%. Thereafter, the rate of PISP + PRSP decreased somewhat to the mid-30% range. Macrolide resistance was also observed; in 2005, the prevalence of strains highly susceptible to erythromycin with MICs ≦ 0.06 μg/ml had decreased to 15.5%, whereas the proportion of highly resistant strains with MICs ≧ 128 μg/ml exceeded 40%. Among Staphylococcus aureus isolates, the proportion of methicillin-resistant S. aureus (MRSA) strains began to increase rapidly in 1986 and constituted around 60% of all S. aureus strains identified in 1990 and in the following years. In 1993, the prevalence of ampicillin-resistant isolates of Haemophilus influenzae had increased remarkably, presumably related to the outbreak of β-lactamase-negative ampicillin-resistant (BLNAR) H. influenzae strains, and the proportion of these strains among the isolates surpassed 30% in 2002 and thereafter. For Klebsiella pneumoniae, the antimicrobial activity of first- to fourth-generation cephems improved with each generation. The MIC distribution patterns of Pseudomonas aeruginosa shifted towards higher MICs when compared with the MICs for other pathogens. Broad patterns with no distinct peaks reflected the difficulty in treating P. aeruginosa infection. Regarding Moraxella catarrhalis, β-lactamase-producing strains already constituted a majority of the isolates in 1990, and the proportion of strains highly susceptible to ampicillin, with MICs ≦ 0.06 μg/ml, was less than 10% at that time.     

Antibacterial activity of carbapenems against clinical isolates of respiratory bacterial pathogens in the northeastern region of Japan in 2007

As the increasing prevalence of resistant strains of respiratory bacterial pathogens has recently been reported, continuous monitoring of the susceptibility of clinical isolates to antibacterial agents is important. We performed a surveillance study focusing on the susceptibility of major respiratory bacterial pathogens in the northeastern region of Japan to carbapenems and control drugs. A total of 168 bacterial strains isolated from patients with respiratory tract infections in 2007 were collected and the minimum inhibitory concentration (MIC) determined. MIC data were subjected to pharmacokinetic/pharmacodynamic analysis with Monte Carlo simulation to calculate the probability of achieving the target of time above MIC with each carbapenem. All Moraxella catarrhalis, Streptococcus pneumoniae, and methicillin-sensitive Staphylococcus aureus isolates were susceptible to carbapenems. Despite the increasing prevalence of β-lactamase-nonproducing ampicillin-resistant strains, all Haemophilus influenzae isolates were susceptible to meropenem. For Pseudomonas aeruginosa, the susceptibility rates for meropenem and biapenem were 76.7%, and the highest probability of achieving pharmacodynamic target (40% of the time above MIC) was obtained with meropenem 0.5 g three times daily as a 4-h infusion (89.4%), followed by meropenem 0.5 g four times daily as a 1-h infusion (88.4%). Carbapenems have retained their position as key drugs for severe respiratory tract infections.     

Administration of antibiotics via the respiratory tract for the prevention of ICU-acquired pneumonia: a meta-analysis of comparative trials

Introduction  

The administration of prophylactic antibiotics via the respiratory tract is one of several strategies for the prevention of intensive care unit (ICU)-acquired pneumonia. We systematically examined the available evidence regarding the effect of prophylactic antibiotics administered via the respiratory tract on the development of ICU-acquired pneumonia, mortality, colonization of the respiratory tract, emergence of antimicrobial resistance, and toxicity.     

Macrolide-resistant Mycoplasma pneumoniae: characteristics of isolates and clinical aspects of community-acquired pneumonia

Mycoplasma pneumoniae is one of the main pathogens causing community-acquired respiratory tract infections in children and adults. Macrolide (ML) antibiotics are recognized generally as first-choice agents for M. pneumoniae infections, and these antibiotics were thought to have excellent effectiveness against M. pneumoniae for many years. In 2000, however, M. pneumoniae showing resistance to macrolides was isolated from clinical samples obtained from Japanese pediatric patients with community-acquired pneumonia (CAP). Since then, prevalence of ML-resistant M. pneumoniae isolates in pediatric patients has increased rapidly. In 2007, ML-resistant M. pneumoniae isolates were obtained from Japanese adults with CAP; numbers of such isolates also have gradually increased in Japan. Recently, similar antimicrobial resistance in M. pneumoniae has begun to emerge worldwide. In this review, we focus on changes of ML-resistant M. pneumoniae from year to year and consider resistance mechanisms as well as clinical features of patients with resistant M. pneumoniae infection.     

Screening of the antibacterial effects of a variety of essential oils on respiratory tract pathogens, using a modified dilution assay method

The purpose of this study was to examine the antibacterial effects of a wide variety of essential oils on major respiratory tract pathogens. The antibacterial activity of 14 essential oils and their major components was evaluated by agar-plate dilution assay under sealed conditions, with agar used as a stabilizer for homogeneous dispersion. Of the selected strains of four major bacteria causing respiratory tract infection, Haemophilus influenzae was most susceptible to the essential oils, followed by Streptococcus pneumoniae and Streptococcus pyogenes. Staphylococcus aureus was less susceptible. No cross-resistance was observed between penicillin-sensitive and penicillin-resistant S. pneumoniae. Escherichia coli, used as a control bacterium, showed the lowest susceptibility. Essential oils containing aldehyde or phenol as a major component showed the highest antibacterial activity, followed by the essential oils containing terpene alcohols. Other essential oils, containing terpene ketone, or ether, had much weaker activity, and an oil containing terpene hydrocarbon was inactive. Based on these findings, thyme (wild, red, and geraniol types), cinnamon bark, lemongrass, perilla, and peppermint oils were selected for further evaluation of their effects on respiratory tract infection. Received: September 29, 2000 / Accepted: April 4, 2001     

Antimicrobial activities of cefditoren against respiratory pathogens isolated from children in Japan

There is an increasing spread and incidence of penicillin-resistant bacteria that are becoming less susceptible to commonly prescribed oral antimicrobials, including extended-spectrum cephalosporins. Against this background, we undertook this study to determine the prevalence of penicillin resistance in Streptococcus pneumoniae and the in-vitro activity of oral antimitrobials. Between April 1996 and December 1997, in 245 children with respiratory tract infections (bronchitis in 61, pharyngitis in 115, and tonsillitis in 69), 119 strains of Haemophilus influenzae, 89 strains of Streptococcus pyogenes, 61 strains of Streptococcus pneumoniae, 36 strains of Staphylococcus aureus, and 34 strains of Moraxella catarrhalis were isolated from the pharynx. The antimicrobial susceptibility of these isolates was assessed by a broth microdilution method. The isolation incidence of penicillin-intermediately resistant S. pneumoniae (PISP) and penicillin-highly resistant S. pneumoniae (PRSP) was 59.0% and 13.1%, respectively. Most strains of PISP and PRSP were highly resistant to cefaclor, cefpodoxime, cefteram, cefdinir, clarithromycin, ampicillin, and minocycline, but susceptibile to ofloxacin and cefditoren (CDTR). The in-vitro activity of CDTR was superior to that of other cephalosporins, such as cefaclor, cefdinir, and cefpodoxime, when tested against both the β-lactamase-positive and -negative H. influenzae isolated. CDTR was also active against all the other strains, including methicillin-sensitive S. aureus, S. pyogenes, and M. catarrhalis. This study suggested that CDTR was a useful oral antibiotic for pediatric respiratory tract infections. Received: June 11, 1998 / Accepted: September 7, 1998     

In-vitro antibacterial activities of cefpiramide and other broad-spectrum antibiotics against 440 clinical isolates in China

The in-vitro antibacterial activity of cefpiramide was compared with those of 15 other broad-spectrum cephalosporins. A total of 440 clinical strains of bacteria, including 9 bacterial species, were isolated from our hospital in 1998. The minimum inhibitory concentrations (MICs) of cefpiramide and five other antibiotics were determined for each species, using the agar-dilution method. The MIC of cefpiramide for Escherichia coli and Klebsiella pneumoniae was higher than those of three other third-generation cephalosporins, (ie, cefoperazone, ceftazidime, and ceftriaxone). Fifty-one percent (26/51) of Enterobacter cloacae isolates were resistant to cefpiramide. Cefoperazone/sulbactam and cefepime had greater activity against E. cloacae (resistance, 3.9% and 19.6%, respectively) than cefpiramide. Cefpiramide was more active against Pseudomonas aeruginosa (resistance rates, 12%) than cefoperazone, ceftazidime, ceftriaxone, aztreonam, and cefepime. Cefpiramide-resistant P. aeruginosa strains were resistant to ceftazidime, but 27% of ceftazidime-resistant strains were susceptible to cefpiramide; 15.3% of cefpiramide-resistant S. maltophilia strains were also susceptible to ceftazidime, but 50% of ceftazidime-resistant strains were still susceptible to cefpiramide. Cefoperazone/sulbactam was the most active agent against Acinetobacter baumannii, showing a resistance rate of 2%. Ampicillin/sulbactam, ceftazidime, and cefpiramide were the second most active agents, and about 50% of the tested strains were susceptible to these three antibiotics. Cefpiramide had an activity comparable to that of all tested β-lactams against oxacillin-susceptible Staphylococcus aureus (MIC₉₀, 2 μg/ml). Against Streptococcus pneumoniae and Haemophilus influenzae, cefpiramide had good activity, with an MIC₉₀ concentration at which 90% of the strain was inhibited of 1 μg/ml and 0.5 μg/ml, respectively. These results indicated that cefpiramide was more active against glucose non-fermenting bacteria than against Enterobacteriaceae, and was very active against oxacillin-susceptible Staphylo-coccus aureus, S. pneumoniae, and H. influenzae. Thus, cefpiramide may be a good choice of drug for the treatment of patients with infections with glucose non-fermenting bacteria and community acquired infections. Received: July 30, 1999 / Accepted: January 24, 2000     

Evaluation of dosing designs of carbapenems for severe respiratory infection using Monte Carlo simulation

Using the Monte Carlo simulation method, the influence of various doses and dosing frequencies of carbapenems on the antimicrobial activities against Streptococcus pneumoniae, Haemophilus influenzae, and Pseudomonas aeruginosa, which are the main causative organisms of respiratory infections, was studied with the aim of identifying optimized effectiveness. Based on pharmacokinetic (PK) parameters of individual carbapenems in healthy adults, data on changes in the respective blood concentrations in 2000 cases were simulated by applying a lognormal distribution to probability distributions of their volume of distributions and half-life periods. Based on minimum inhibitory concentration (MIC) distribution data of the individual carbapenems against these strains, MICs in the 2000 cases were also simulated. Using these data in blood concentrations and MICs, the probabilities of attaining various percentages of the dosing interval during which drug concentrations remain above MIC (T > MIC) were calculated at several dosing regimens. Considering the probabilities of attaining the bactericidal effect (50% T>MIC) and daily drug costs, imipenem (IPM) at 500 mg i.v. BID, panipenem (PAPM) at 500 mg i.v. BID, and biapenem (BIPM) at 300 mg i.v. BID against Streptococcus pneumoniae; meropenem (MEPM) at 500 mg i.v. BID or TID against Haemophilus influenzae infections; and MEPM at 500 or 1000 mg i.v. TID against Pseudomonas aeruginosa, each over 30 min, were determined as appropriate empirical treatments. Selecting carbapenems with superior antimicrobial activities and optimizing their dose regimens are important to improve the efficacy. Application of Monte Carlo simulation to MIC distributions allows determination of appropriate empiric therapy even if drug susceptibility of a causative organism in individual patients is unknown.     

Bacterial translocation of intestinalPseudomonas aeruginosa in post-burn infection of mice

The significance of intestinalPseudomonas aeruginosa as a pathogen of post-burn infection in mice was established. Mice with and withoutP. aeruginosa intestinal colonization were scorched with a deep dermal burn by ethanol flame on the shaven back, involving approximately 25% of the total body surface area. Eight hours later,P. aeruginosa of a serotype similar to that previously administered (per os) was detected in the burn site, liver, and spleen ofP. aeruginosa-treated, but not the control, animals. Within three post-burn days, 33.3% of theP. aeruginosa-treated, burned mice died of infection-derived sepsis, whereas none of the control mice died. In addition, when the orally nonabsorbable antibiotics, polymyxin B (12 mg/kg) and vancomycin (30 mg/kg), were administered by intragastric injection toP. aeruginosa-treated mice immediately after burn exposure, the mortality rate significantly decreased to 16.1±6.1% compared with 35.0±5.0% in similarly colonized, burned mice not given these oral antibiotics (P<0.05). These findings suggest thatP. aeruginosa colonized in the intestinal tract is noxious and can be fatal as a pathogen of post-burn infection. Furthermore, our report suggests that selective digestive decontamination (decontamination of endogenous pathogens in the intestinal tract) is essential in preventing post-burn infection associated with bacterial translocation.