Clinical resistance to penicillin in Streptococcus pneumoniae was first reported by researchers in Boston in 1965; subsequently, this phenomenon was reported from Australia (1967) and South Africa (1977). Since these early reports, penicillin resistance has been encountered with increasing frequency in strains of S. pneumoniae from around the world. In South Africa strains resistant to penicillin and chloramphenicol as well as multiresistant strains have been isolated. Similar patterns of resistance have been reported from Spain. Preliminary evidence points to a high prevalence of resistant pneumococci in Hungary, other countries of Eastern Europe, and some countries in other areas of Europe, notably France. In the United States most reports of resistant pneumococci come from Alaska and the South, but resistance is increasing in other states and in Canada. Pneumococcal resistance has also been described in Zambia, Japan, Malaysia, Pakistan, Bangladesh, Chile, and Brazil; information from other African, Asian, and South American countries is not available. The rising prevalence of penicillin-resistant pneumococci worldwide mandates selective susceptibility testing and epidemiological investigations during outbreaks.

Antimicrobial Resistance in Streptococcus pneumoniae: An Overview

In 1990 it was estimated that 4123 million of the world's 5267 million population—78%—lived in developing countries. Of the 39.5 million deaths in the developing world, 9.2 million were estimated to have been caused by infectious and parasitic disease; infections of the lower respiratory tract were the third most common cause of death worldwide, and diarrhoeal diseases were the fourth.1 Ninety eight per cent of deaths in children occur in the developing world, mostly as a result of infections.

Projections of disability adjusted life years (that is, the years of life without disability) for the year 2020 show great improvement in developing regions: people are living longer without disabilities.2 However, even the most pessimistic model analysed did not take into account the possibility that the development of new antimicrobial drugs might slow or cease, and that rates of drug resistance in bacteria such as pneumococci, Mycobacterium tuberculosis , or Staphylococcus aureus might increase. We chart the progress and impact of bacterial resistance to antimicrobial drugs in the developing world. The information in this review has been assembled from searches of the computerised databases Medline and Bath Information and Data Services, discussions with colleagues, and personal knowledge.

#### Summary points

Although even the most potent and recently developed antimicrobial drugs are available throughout the world, …

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Antimicrobial resistance in developing countries.

Background Penicillin-resistant strains of Streptococcus pneumoniae are now found worldwide, and strains with resistance to cephalosporin are being reported. The appropriate antibiotic therapy for pneumococcal pneumonia due to resistant strains remains controversial. Methods To examine the effect of resistance to penicillin and cephalosporin on mortality, we conducted a 10-year, prospective study in Barcelona of 504 adults with culture-proved pneumococcal pneumonia. Results Among the 504 patients, 145 (29 percent) had penicillin-resistant strains of S. pneumoniae (minimal inhibitory concentration [MIC] of penicillin G, 0.12 to 4.0 μg per milliliter), and 31 patients (6 percent) had cephalosporin-resistant strains (MIC of ceftriaxone or cefotaxime, 1.0 to 4.0 μg per milliliter). Mortality was 38 percent in patients with penicillin-resistant strains, as compared with 24 percent in patients with penicillin-sensitive strains (P = 0.001). However, after the exclusion of patients with polymicrobial pneumonia an...

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Resistance to penicillin and cephalosporin and mortality from severe pneumococcal pneumonia in Barcelona, Spain.

Multiple antimicrobial resistance in pneumococci was detected in Johannesburg in July, 1977, and prompted an investigation of the prevalence of resistant strains in two hospitals. Carriers of Types 6A and 19A penicillin-resistant pneumococci, resistant to antibiotic concentrations ranging between 0.12 and 4 microgram per milliliter were found in 29 per cent of 543 pediatric patients and 2 per cent of 434 hospital staff members. Multiply resistant Type 19A strains, resistant to beta-lactam antibiotics, erythromycin, clindamycin, tetracycline and chloramphenicol, were isolated from 128 carriers, and were responsible for bacteremia in four patients. Isolates from 40 other carriers were resistant to penicillin alone or to penicillin and chloramphenicol or to penicillin, chloramphenicol and tetracycline. Pneumococci can be screened for penicillin resistance with a modified Kirby--Bauer technic; the strains with zones of less than 35 mm around 6-microgram penicillin disks or less than 25 mm around 5-microgram methicillin disks should be tested for sensitivity to penicillin by measurements of minimum inhibitory concentration.

Emergence of multiply resistant pneumococci.

Streptococcus pneumoniae, type 23F, resistant to penicillin (MIC, 2 micrograms/mL) and multiple other antimicrobic agents, was isolated from middle ear fluid of a child with otitis media attending a day care center in Ohio. To determine the extent of spread of this strain, nasopharyngeal culture surveys were done, and 52 carriers were identified among 250 children attending the index day care center. No carriers were found among 121 children at two other day care centers in the same urban area. Use of prophylactic doses of antibiotics (P < .001) and frequent use of antibiotics (P < 0.001) were risk factors for nasopharyngeal carriage. Carriers were more likely to have had frequent otitis media episodes (P < .02) and otitis media not responsive to antimicrobial therapy (P < .001). Strategies to limit the spread of highly resistant pneumococcal strains should include encouraging judicious use of antimicrobic agents and reevaluating indications for prophylactic use of antimicrobic agents.

The Spread of Multiply Resistant Streptococcus pneumoniae at a Day Care Center in Ohio

Streptococcus pneumoniæ resistant to penicillin and chloramphenicol

of possible tuberculous infection than a contrast series: and that it approaches that of a group of patients suffering from pulmonary tuberculosis. Bass and Vader (1957), in Eindhoven, collected a series of 128 patients with sarcoidosis, the diagnosis being made on clinical grounds mainly, biopsy evidence being positive in 16. Contact with active tuberculosis, often with longer intervals than two years, within and without the family totalled 23 (18%), to which they added contact with inactive tuberculosis in 17 (13%X,) and with cattle in 6 (5%), giving them a total of 36% with tuberculous contacts; both latter groups were inaccessible in our patient questionary retrospective survey. It seems that their higher incidence may be partly due to different means of selection of the patients, different definition of contact history, and the advantages of a full radiological survey of the possible contacts. These significant findings clearly bear upon the problem of the part which tuberculous infection may play in the genesis of sarcoidosis. They suggest that contact with tuberculosis may well be a substantial rather than a minor cause; for, if the contact history is a mere coincidence, it is difficult to explain why it should differ from that of the contrast group. This evidence of a relationship between tuberculous infection and the onset of sarcoidosis raises many further problems. It may, for instance, well be that the role of infection with M. tutbercuiilosis is catalytic for an immune process of a highly specific type. Evidence for altered immune reactions in patients with active sarcoidosis has been recorded by Greenwood et al. (1958). The familial aspects of tuberculosis in this series of patients with sarcoidosis lends support to this in that there seems to be some evidence of inherited resistance to tuberculosis. There are five families in this series with sarcoidosis. The relationship is close in all of them, and yet in only one of these families is another relative known to have tuberculosis, and there the contact was not recent. Although this is a small experience it does suggest that there may well be an immune process which is determined genetically. There seems to be a place for a longer survey of the contacts of patients with tuberculosis, particularly where the population is compact and stable.

https://www.bmj.com/content/bmj/2/5215/1759.full.pdf

Kwashiorkor in African children in Durban.

Shigella infection in African and Indian children with special reference to Shigella septicemia

A prospective study was undertaken over a period of six months to determine the spectrum of infection, sensitivity of organisms isolated, and suitability of antibiotics chosen in 520 consecutive patients admitted to a paediatric unit. Culture and sensitivity of stool, urine and blood yielded 752 isolates; in 147 cases, more than one pathogen was isolated from the same or different sites. High rates of resistance to chloramphenicol, ampicillin, and kanamycin were seen in salmonellae other than Salmonella typhi, which differed in retaining its original sensitive susceptibility profile. Most Enterobacteria were sensitive to gentamicin. Penicillin-resistance was seen in 9% of meningococci, and several Haemophilus influenzae strains (20%) were resistant to ampicillin. Methicillin-resistance was encountered in 13% of Staphylococcus aureus strains and 17% of pneumococci were resistant to penicillin G. The sensitivity pattern of organisms isolated was probably directly related to widespread use of antibiotics.

J.N. Scragg

Papers

Streptococcus pneumoniæ resistant to penicillin and chloramphenicol

Kwashiorkor in African children in Durban.

Shigella infection in African and Indian children with special reference to Shigella septicemia

The spectrum of infection and sensitivity of organisms isolated from African and Indian children in a Durban hospital

Serum vitamin B12 concentrations in megaloblastic anemia associated with kwashiorkor and marasmus.