Author: David Hansman
Hansman, David, 2024 Antimicrobial drug resistance in pneumococcus Streptococcus pneumoniae, Flinders University, College of Medicine and Public Health
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The studies described here include the first reports of antibiotic resistance in the pneumococcus Streptococcus pneumoniae. The development of resistance was important clinically because of the high prevalence of pneumococcal infections, especially pneumococcal pneumonia, which, in low and middle income countries, was often fatal in both children and adults. When these studies began, in the 1960’s, pneumococcal pneumonia was probably the commonest infectious cause of death in these countries
Of other serious infections caused by pneumococci, meningitis was especially important. The pneumococcus was a leading cause of bacterial meningitis in both children and adults, with high mortality rates in all regions. Survivors often suffered from permanent sequelae, including mental impairment and severe deafness.
The first drugs effective and safe in the treatment of pneumococcal infections were the sulphonamides, introduced in the 1930’s. These proved useful in a variety of infections, including pneumococcal pneumonia. Although by the early 1940’s sulphonamide resistance was becoming more common, penicillin, introduced in 1944, proved even more effective In the treatment of pneumococcal infections.
When my studies began, in the 1960’s, several antibiotics were available for the treatment of pneumococcal and streptococcal infections: tetracyclines, chloramphenicol, erythromycin and lincomycin, as well as penicillin. Resistance to these agents was unknown, so pneumococcal infections, including bacteraemic pneumonia and meningitis, could be treated with these antibiotics, with the confidence that most patients would respond well to therapy.
Parenteral penicillin was the antibiotic usually given in severe pneumococcal infections. Any material decrease in susceptibility was potentially important. This was especially so in patients with pneumococcal meningitis: because of the blood brain barrier, penetration of penicillin into cerebrospinal fluid [CSF] is poor.
Amongst other antibiotics used to treat pneumococcal infections in the 1960’s, the tetracyclines were prominent. In 1963 Evans and I reported the isolation of a tetracyclineresistant pneumococcus, from the CSF of a young child with meningitis. This was soon followed by reports of similar strains from the United Kingdom [UK]. It had long been recognised that pneumococci could cause family and institutional outbreaks of pneumococcal infection. In 1963/64 a hospital outbreak of pneumococcal
respiratory disease, including cases of pneumonia, caused by tetracycline-resistant pneumococci of several serotypes occurred in Sydney, which Andrews and I reported. Also in 1963, a similar hospital outbreak caused by a tetracycline-resistant pneumococcus occurred in the UK.
The first report of a pneumococcus with reduced susceptibility to penicillin, from a young woman with hypogammaglobulinaemia, was made in 1967, by Bullen and me. Subsequently, studies of pneumococci isolated from New Guineans in 1969, and later, showed that pneumococci with reduced susceptibility to penicillin were relatively common in Papua New Guinea [PNG]. These RSP pneumococci, which belonged to several serotypes, were present in coastal, highland and island communities. That such strains
could be fully virulent was shown by their isolation from patients with fatal infections.
Some seven years elapsed before reports appeared of RSP strains in other regions. From 1974 pneumococci with reduced susceptibility to penicillin were reported from the United States [US], UK, Canada and South Africa.
In 1978 I reported the isolation of pneumococci showing dual or multiple drug resistance, from patients in Adelaide, Melbourne and Sydney, during the four-year period, 1972 through 1975. Several resistance patterns were encountered, involving chloramphenicol, erythromycin, lincomycin, penicillin and tetracycline.
Once widespread drug resistance had been demonstrated, in the 1970’s, clinical laboratories began to test the susceptibility of clinical isolates to penicillin and other antibiotics. This was of particular importance in patients with severe infections, especially bacteraemic pneumonia, meningitis and other invasive infections, so that inappropriate chemotherapy could be avoided. It could no longer be assumed that pneumococci were invariably susceptible to antibiotics.
Fortunately, the introduction of first polysaccharide and then conjugated pneumococcal vaccines provided an effective method of preventing pneumococcal infections. This was especially important in infants and young children in whom the bulk of invasive pneumococcal disease occurs.
Keywords: ANTIMICROBIAL, DRUG RESISTANCE, PNEUMOCOCCUS, STREPTOCOCCUS, PNEUMONIAE
Subject: Medicine thesis
Thesis type: Doctor of Philosophy
Completed: 2024
School: College of Medicine and Public Health
Supervisor: Professor David Gordon