Pneumococcal disease in the Maltese islands: focus on drug-resistance

Abstract

Drug-resistance can be visualized as a modem global threat, which is menancing world populations. Common infections, which for decades have been treated successfully with antimicrobial agents, do not respond to treatment, as microorganisms acquire resistance. Streptococcus pneumoniae is a Gram-positive bacterium, which commonly infects young children (notably, those \< 5years), as well as the elderly (>/60 years). Immunocompromised people, typically those with sickle-cell disease, splenectomy as well as other predisposing conditions, are also targets for pneumococcal infections. Important risk factors for developing a drug-resistant Str. pneumoniae (DRSP) infection, (in addition to the ones mentioned above), includes: previous antibiotic use, day-care centre attendance, clonal dissemination and inhabiting a high prevalence area. (Lynch, 1999) In the United States alone, it has been estimated that annually, there are more than 7 million cases of otitis media, 500,000 cases of pneumonia, 50,000 cases of bacteraemia and 3,000 cases of meningitis, due to Str. pneumoniae. (CDC, 1995) Pneumococcal infections are responsible for about one million deaths annually, among very young children worldwide, especially in developing countries. (Health Horizons 1999/2000) The first occurrence of Drug-resistant Streptococcus pneumoniae (DRSP) dates back to 1969, in the remote village of Anguganak, New Guinea. Here, a penicillin-resistant isolate (capsular type 4) was isolated from a three-year old child. (Tomasz A, 1999) Subsequently, resistant strains appeared in South Africa, United States, Europe and all throughout the rest of the world. The most widely spread epidemic clones of DRSP include the Spanish/USA serotype 23F, serotypes 14, 9V and 6B. Mechanisms of resistance depend on the antibiotic. Hence, pneumococcal resistance to penicillin is manifested by a change in the affinity of the penicillin-binding proteins (PBPs). Other mechanisms of resistance, as in macrolide antibiotics, include active efflux (encoded by the mefE gene) and target site modification (encoded by ermAM). The presence of an ermAM gene confers resistance to all macrolide antibiotics and this is described as MLSB (macrolides, azalides, lincosamides, streptogramin B-type antibiotics) phenotype. This work investigated the local scenario for DRSP and to establish the resistance rates for different antibiotics. In addition, information retrieved from patient medication records sought to portray whether particular trends were evident and consistent with resistant strains. Finally, antibiotic usage (calculated in defined daily doses) during the years 1997- 2000, for the government health services were obtained. It was shown that, highest consumption rates were obtained with co-amoxiclav, followed by amoxicillin, erythromycin, cephalexin and ciprofloxacin. Hence, during the period September 2000 up to April 2002, 129 a-haemolytic strains were collected and tested. From these, 74 were proven to be pneumococcal strains. In total, 50% (37174) of the strains proved to be resistant to at least one of the antibiotics tested. Penicillin-intermediately resistant strains (ie 0.12-1.0Jlg/ml, NCCLS Jan 2002) accounted for 27% (20174) of cases. Highly-resistant penicillin strains (ie >/ 2.0µg/ml, NCCLS Jan 2002) were not isolated. Pneumococcal isolates demonstrating resistance to erythromycin equalled 31.1 % (23/74). In addition, high-level resistance to erythromycin and clindamycin accounted for 18.9% (14174) of all the pneumococci isolated. Overall, isolates demonstrating multidrug-resistance to penicillin, erythromycin and clindamycin accounted for 8.1 % (6/74) of all isolates.

Even though the number of isolates tested was not large, these findings are still alarming and clearly indicate that DRSP is present in the Maltese Islands. This study hence calls for: • More judicious usage of antibiotics • Establishment of policies which should reflect these findings and which should be updated periodically • Vaccination schedules which should include pneumococcal vaccines for target populations • Local on-going surveillance programmes which monitor assiduously DRSP liasing closely with similar institutions in other countries • Educating the general public as well as health care professionals on DRSP, as well as drug-resistant infections, in general.