The synthesis of large numbers of antibiotics over the past three decades has caused complacency about the threat of bacterial resistance. Bacteria have become resistant to antimicrobial agents as a result of chromosomal changes or the exchange of the exchange of genetic material via plasmids and transposons. Streptococcus pneumoniae, Streptococcus pyogenes, and staphylococci, organisms that cause respiratory and cutaneous infections, and members of the Enterobacteriaceae and Pseudomonas families, organisms that cause diarrhea, urinary infection, and sepsis, are now resistant to virtually all of the older antibiotics. The extensive use of antibiotics in the community and hospitals has fueled this crisis. Mechanisms such as antibiotic control programs, better hygiene, and synthesis of agents with improved antimicrobial activity need to be adopted in order to limit bacterial resistance.

https://science.sciencemag.org/content/sci/257/5073/1064.full.pdf

The Crisis in Antibiotic Resistance

In the last several years, the frequency and spectrum of antimicrobial-resistant infections have increased in both the hospital and the community. Certain infections that are essentially untreatable have begun to occur as epidemics both in the developing world and in institutional settings in the United States. The increasing frequency of drug resistance has been attributed to combinations of microbial characteristics, selective pressures of antimicrobial use, and societal and technologic changes that enhance the transmission of drug-resistant organisms. Antimicrobial resistance is resulting in increased morbidity, mortality, and health-care costs. Prevention and control of these infections will require new antimicrobial agents, prudent use of existing agents, new vaccines, and enhanced public health efforts to reduce transmission.

https://science.sciencemag.org/content/sci/257/5073/1050.full.pdf

Epidemiology of Drug Resistance: Implications for a Post—Antimicrobial Era

Background Before the introduction of the conjugate vaccines, Haemophilus influenzae type b was the major cause of bacterial meningitis in the United States, and meningitis was primarily a disease of infants and young children. We describe the epidemiologic features of bacterial meningitis five years after the H. influenzae type b conjugate vaccines were licensed for routine immunization of infants. Methods Data were collected from active, population-based surveillance for culture-confirmed meningitis and other invasive bacterial disease during 1995 in laboratories serving all the acute care hospitals in 22 counties of four states (total population, more than 10 million). The rates were compared with those for 1986 obtained by similar surveillance. Results On the basis of 248 cases of bacterial meningitis in the surveillance areas, the rates of meningitis (per 100,000) for the major pathogens in 1995 were Streptococcus pneumoniae, 1.1; Neisseria meningitidis, 0.6; group B streptococcus, 0.3; Listeria mono...

Bacterial Meningitis in the United States in 1995

Background In the early 1990s there was an increase in erythromycin resistance among group A streptococci in Finland. In response, policies regarding outpatient antibiotic therapy were changed, and nationwide recommendations were issued that called for reductions in the use of macrolide antibiotics for respiratory and skin infections in outpatients. We studied the effect of this policy on the pattern of erythromycin resistance throughout Finland. Methods From 1991 through 1996, a total of 39,247 group A streptococcal isolates from throat swabs (82 percent of the isolates) and pus samples (18 percent) and 290 isolates from blood cultures were studied in regional microbiology laboratories. The susceptibility of the isolates to erythromycin was tested by the disk-diffusion or the screening-plate method. Results Consumption of macrolide antibiotics decreased from 2.40 defined daily doses per 1000 inhabitants per day in 1991 to 1.38 in 1992 (P = 0.007) and remained near the lower level during the study period....

The Effect of Changes in the Consumption of Macrolide Antibiotics on Erythromycin Resistance in Group A Streptococci in Finland

Background Fluoroquinolones are now recommended for the treatment of respiratory tract infections due to Streptococcus pneumoniae, particularly when the isolates are resistant to β-lactam antibiotics. Although pneumococci with reduced susceptibility to fluoroquinolones have been identified, their prevalence has not been determined in a defined population. Methods We performed susceptibility testing on 7551 isolates of S. pneumoniae obtained from surveillance in Canada in 1988 and from 1993 to 1998. Pneumococci with reduced susceptibility to fluoroquinolones (defined as a minimal inhibitory concentration of ciprofloxacin of at least 4 μg per milliliter) were further characterized. We also examined antibiotic prescriptions dispensed in Canadian retail pharmacies. Results Between 1988 and 1997, fluoroquinolone prescriptions increased from 0.8 to 5.5 per 100 persons per year. The prevalence of pneumococci with reduced susceptibility to fluoroquinolones increased from 0 percent in 1993 to 1.7 percent in 1997 a...

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Decreased Susceptibility of Streptococcus pneumoniae to Fluoroquinolones in Canada

The oropharyngeal carriage of Haemophilus influenzae type b (Hib) was studied among 725 healthy 3-year-old children who had or had not been immunized with an Hib conjugate vaccine. Oropharyngeal swabs were collected during the childrens' well-child visit to their local child health center. Fourteen (3.5%) of the 398 unvaccinated children were oropharyngeal carriers of Hib, whereas none of the 327 children who had received Hib conjugate vaccine carried Hib (P less than .001). Carriage rates of non-type b H. influenzae (19%) or Streptococcus pneumoniae (18%) were the same irrespective of the Hib vaccination status of the children. Thus Hib conjugate vaccine, unlike Hib polysaccharide vaccine, seems to be able to prevent oropharyngeal colonization by Hib.

Reduction of Oropharyngeal Carriage of Haemophilus influenzae Type b (Rib) in Children Immunized with an Rib Conjugate Vaccine

Background. The use of erythromycin in Finland nearly tripled from 1979 to 1989. In 1988, we observed an unusually high frequency of resistance to erythromycin in group A streptococci in one geographic region. Because routine testing does not detect the sensitivity of these organisms to antibiotics, we initiated a national study to evaluate the extent of this resistance. Methods. We studied 272 isolates of group A streptococci obtained from blood cultures from 1988 through 1990. In 1990 we collected from six regional laboratories 3087 consecutive isolates from throat swabs and 1349 isolates from pus samples. Resistance was indicated by growth on blood agar containing 2 μg of erythromycin per milliliter after incubation in 5 percent carbon dioxide. We also evaluated the clinical importance of erythromycin resistance in a retrospective study of consecutive patients with pharyngitis. Results. The frequency of resistance to erythromycin in group A streptococci from blood cultures increased from 4 per...

https://www.nejm.org/doi/pdf/10.1056/NEJM199201303260503

Resistance to erythromycin in group A streptococci.

Three different phenotypes of erythromycin-resistant Streptococcus pyogenes in Finland

Respiratory and otitis isolates of 807 Streptococcus pneumoniae, 816 Haemophilus influenzae and 446 Moraxella catarrhalis were collected from 21 clinical microbiology laboratories for antimicrobial susceptibility testing in 1995. After a period of relative stability in 1981 and 1987-1990, beta-lactamase production increased in H. influenzae. Among middle ear isolates from children under 6 years, beta-lactamase production increased from 8% to 24% in H. influenzae and from 81% to 96% in M. catarrhalis since the survey in 1987-1990. 1.2% of S. pneumoniae were penicillin-resistant and 4.2% intermediately resistant; 5 years earlier among otitis isolates of children only 1.7% intermediate resistance was found. Ampicillin resistance was seen among 1.9% of non-beta-lactamase-producing strains of H. influenzae. Resistance to trimethoprim-sulphamethoxazole occurred in 9.4% of S. pneumoniae, 7.4% of H. influenzae and 0.7% of M. catarrhalis. Frequencies of azithromycin resistance were 3.0% in S. pneumoniae and 1.6% in H. influenzae, and those of tetracycline resistance were 6.7% in S. pneumoniae and 1.2% in H. influenzae.

Increasing antimicrobial resistance in Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis in Finland.

The frequency of beta-lactamase production was analyzed in a study of 1,452 strains of Moraxella catarrhalis and 2,738 strains of Haemophilus influenzae isolated from middle-ear fluid of children < 6 years of age at Tampere University Hospital in Tampere, Finland, between 1978 and 1993. In addition, 401 isolates of M. catarrhalis from similar samples collected in different parts of Finland in 1988-1990 were tested for beta-lactamase production; minimal inhibitory concentrations of ampicillin, cefaclor, cephalothin, erythromycin, tetracycline, and trimethoprim-sulfamethoxazole for these strains were determined. These data were compared with figures for the annual consumption of beta-lactam antimicrobials in the community in 1978-1993. A bimodal increase in the proportion of strains of M. catarrhalis producing beta-lactamase was detected: from 0 to 60% in 1978-1983 and from 60% to 80% in 1988-1990. Concurrently with the second increase, the consumption of cephalosporins increased substantially in the community. The frequency of beta-lactamase-producing strains of H. influenzae did not increase between 1978 and 1993.

Antti Nissinen

Papers

Reduction of Oropharyngeal Carriage of Haemophilus influenzae Type b (Rib) in Children Immunized with an Rib Conjugate Vaccine

Resistance to erythromycin in group A streptococci.

Three different phenotypes of erythromycin-resistant Streptococcus pyogenes in Finland

Increasing antimicrobial resistance in Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis in Finland.

Development of β-Lactamase-Mediated Resistance to Penicillin in Middle-Ear Isolates of Moraxella catarrhalis in Finnish Children, 1978–1993