Antibiotic resistance to pneumococcal meningitis.
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Biomedical subjects
Publications and source records attributed to G L French.
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The biliary excretion of imipenem-cilastatin studied by endoscopic cannulation of the common bile duct in patients with complete obstruction and in a group without obstruction showed that despite a 24-h prophylaxis, the bile obtained from patients with obstruction immediately after cannulation contained neither imipenem nor cilastatin, while there were 2 and 5% of peak concentrations in serum for imipenem and cilastatin, respectively, in the bile from patients without obstruction. Biliary excretion of both compounds increased rapidly after decompression, reaching a maximum of 15% of peak levels in serum within 2 h. Twenty-four hours after drainage, the biliary excretion of the drugs further improved. We conclude that since biliary obstruction impairs excretion of antibiotics, drainage is necessary for the control of sepsis in obstructed cholangitis.
A typhoid patient was infected with a fully-sensitive, plasmidless strain of Salmonella typhi which acquired resistance to kanamycin, sulfamethoxazole and trimethoprim during cotrimoxazole therapy. The resistant post-treatment strain harboured 4 plasmids of 62, 4.1, 3.8 and 3.0 Md in size. Kanamycin-, sulfamethoxazole- and trimethoprim-resistance were borne on a transferable 62 Md plasmid which was compatible with groups FI, FIme, FII, FIV, H1, H2, B, I1, I2, J, K, M, N, T, X, W and P. Sulfamethoxazole-resistance was also borne on the 4.1 Md plasmid. The 3.8 Md plasmid was not transferable; the 3.0 Md plasmid was transferable but did not confer antibiotic resistance. Excluding the strain described here, only 5 out of 35 other S typhi isolates contained plasmids. This is the first report of trimethoprim-resistant S typhi in Hong Kong.
Data from seven single-day prevalence surveys were used to assess the costs of hospital-acquired infection (HAI) by matching infected cases with controls and reviewing patient case notes for details of mortality, length of hospitalization and antibiotic treatment costs. Many cases with a high risk of HAI could not be matched and probably had inevitable infection. Cases that could be matched had the same risks of HAI as the controls, and these infections were potentially avoidable. Compared with controls, infected patients had an excess mortality rate of 7.4%, an average excess hospital stay of 23 days and an average excess antibiotic expenditure of US$190. By extrapolation we calculate that the annual costs of avoidable HAI at Prince of Wales Hospital is now approximately 130 lives, 42 000 bed-days and US$0.3m of antibiotics; costs of a similar magnitude have already been saved by a programme of hospital infection control. We conclude that hospital-acquired infection is very expensive, infection control is highly cost-effective, and prevalence surveys are practical tools for the measurement of rates and costs of hospital infection.
The storage, retrieval and analysis of hospital infection data is best performed by using computers. Many laboratory mainframe systems have infection control modules and there are some commercial programs for personal computers (PCs). An alternative is to use business and statistical PC software. Because of their large customer base these programs are reliable and easy to use yet extremely sophisticated and flexible, and they can be easily customized for use in infection control. Many combinations of software and hardware are available but the ones described here have been used successfully for several years at the Prince of Wales Hospital in Hong Kong.
We investigated the pharmacokinetics of two intravenous (iv) dose regimens of imipenem/cilastatin in Chinese patients on chronic ambulatory peritoneal dialysis (CAPD), who had an average creatinine clearance of 3.2 ml/min/1.73 m2. Doses of 0.5 and 1.0 g produced mean peak serum imipenem concentrations of 30 and 70 mg/l respectively, about 60% of cilastatin. Peritoneal dialysis fluid (PDF) imipenem concentrations reached 20-30% of the serum peak 4-5 h after iv injection, and the lowest maximum PDF concentrations were 2 mg/l after the 0.5 g dose and 14 mg/l after 1.0 g. Thus both regimes produced PDF imipenem concentrations above the MICs of susceptible pathogens. The half-life of imipenem was 6.4 h and the plasma clearance 66 ml/min; serum and PDF imipenem were in equilibration after about 5 h. Cilastatin had a prolonged half-life of 19 h and a plasma clearance of 10 ml/min, and accumulated in both serum and PDF. With a 0.5 g dose, the pharmacokinetics of imipenem/cilastatin suggest that the combination may prove an effective treatment for peritonitis associated with CAPD.
We examined the in-vitro antibiotic susceptibility of 760 gastroenteric salmonellae and 36 strains of Salmonella typhi isolated in Hong Kong between 1985 and 1988. S. typhi remained susceptible to all the antibiotics tested except for one isolate resistant to chloramphenicol, another to kanamycin and co-trimoxazole, and a third to nalidixic acid. In contrast, resistance and multiple resistance has increased significantly in gastroenteric salmonellae over the last ten years. Seventeen percent were resistant to ampicillin, 61% to tetracycline, 23% to chloramphenicol and 8% to gentamicin. Many ampicillin-resistant strains remained resistant to ampicillin even in the presence of sulbactam (69%) or clavulanic acid (25%). More than 50% of isolates were resistant to two or more antibiotics and one isolate was resistant to eleven. Ampicillin-resistance was usually due to the production of TEM-1 or OXA-1 beta-lactamases but a few isolates produced AER-1, PSE-1 or PSE-2. Genetic determinants for these enzymes were usually borne on plasmids ranging in size from 2 to 143.7 Md but half of the OXA-1 genes were chromosomally located.
Detection of TBSA was attempted in pleural aspirates of 74 patients with tuberculous and 44 patients with nontuberculous pleural effusion by gas chromatography/mass spectrometry with selected ion monitoring. The results were disappointing with a test sensitivity of 67.6 percent and a specificity of 52.3 percent. In contrast, histologic examination of pleural biopsies gave a diagnostic sensitivity of 71.0 percent. Pleural biopsy remains a better investigational procedure for the diagnosis of tuberculous pleural effusion.
In a 5-year prospective study in a Hong Kong teaching hospital there were 344 clinically significant episodes of paediatric septicaemia. Many of the microbiological and clinical features were similar to those reported in Japanese and Western studies but there were some important differences. Half of the episodes (or 70% if neonatal infections are excluded) were community-acquired. The commonest organisms found were Salmonella spp (15% of all and 27% of community-acquired infections); this was related to the high local incidence of salmonellosis and typhoid fever. Salmonella typhi, which was responsible for one-third of the salmonella septicaemias, was usually seen in school-age children, while non-typhoid salmonellae were common in infants. Methicillin-resistant Staphylococcus aureus, which are now endemic in Hong Kong hospitals, was a common cause of hospital-acquired septicaemia. Pneumococcal septicaemia accounted for 22% of episodes in infants and pre-school children, but Haemophilus influenzae was uncommon (2% of all episodes) and there was no case of meningococcal septicaemia. The rarity of invasive infection with H. influenzae and Neisseria meningitidis in Hong Kong children is unexplained.
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Infective endocarditis caused by Streptococcus suis serotype 2 is not uncommon in pigs but is rare in human beings. We describe the case of a pig-farmer with endocarditis due to S. suis serotype 2 and in whom prolapse of the mitral valve was the predisposing cardiac lesion. Streptococcus suis, a possible cause of infective endocarditis in endemic areas, may be confused with other group D streptococci. In suspected cases a history of contact with pigs or raw pork should be sought.
While most authorities agree that methicillin-resistant Staphylococcus aureus (MRSA) are as pathogenic as methicillin-sensitive strains (MSSA), some believe that MRSA are relatively avirulent opportunists, and that their importance has been exaggerated. We present evidence that Hong Kong strains of MRSA and MSSA are equally pathogenic: they have similar virulence in animal models; they are isolated in similar proportions from both deep and superficial clinical sites including blood; in patients with hospital-acquired bacteraemias mortality rates are similar when adjusted for clinical factors; and in both animals and patients with systemic MRSA infection, mortality rates are significantly reduced by vancomycin therapy. Efforts to control the spread of MRSA are justified, and in invasive sepsis early treatment with vancomycin may be life-saving.
Multiple introductions of methicillin-resistant Staphylococcus aureus (MRSA) strains occurred to a new hospital in Hong Kong. Two years of clinical microbiological surveillance of the resulting outbreaks was combined with laboratory investigation by phage and antibiogram typing, and plasmid profiling. The outbreaks on the special care baby (SCBU) and burns (BU) units were studied in detail, and colonization of staff and contamination of the environment were investigated. MRSA were spread by the hands of staff on the SCBU, where long-term colonization of dermatitis was important, but were probably transmitted on the BU by a combination of the airborne, transient hand-borne and environmental routes. Simple control measures to restrict hand-borne spread on the SCBU were highly effective, but control was not successful on the BU.
The biliary excretion of cefoperazone and ceftazidime was studied by endoscopic cannulation of the common bile duct, in patients with complete biliary obstruction and in an unobstructed control group. Patients were given each drug prophylactically for 24 h before endoscopy and as a single dose at the time of cannulation. In unobstructed patients biliary excretion of ceftazidime was passive. At the time of cannulation bile contained 10% of the peak serum concentration, rising to 20% 90 min later. Cefoperazone excretion was active. At cannulation biliary concentrations were 200% of the serum peak, 900% at 60 min and 700% at 90 min. In obstructed patients, bile sampled immediately at decompression contained neither antibiotic. Passive excretion of both drugs occurred rapidly after relief of obstruction and biliary concentrations were 20% of maximum serum levels at 60 min. Twenty-four hours later passive excretion had further improved, but the active excretion mechanism of cefoperazone had still not recovered. We conclude that obstruction impairs active as well as passive biliary excretion of antibiotics, that drainage is essential for the control of sepsis in obstructed cholangitis, and that both cefoperazone and ceftazidime achieve similar and therapeutic concentrations in bile during the 24 h after decompression.
In a five-year prospective study of blood culture-positive septicaemia in a Hong Kong teaching hospital there were 2211 clinically-significant episodes, of which 16% occurred in children less than 15 years old. The microbiology and clinical features were broadly similar to those seen in Europe and North America, but with some important differences. Two-thirds of episodes were community-acquired. The most common organism isolated from community-acquired septicaemias was Escherichia coli and the source, most commonly, the urinary tract. However, the biliary tract was the second most common source of community-acquired infection (25%), reflecting the frequency of liver disease in Hong Kong. Three per cent of community-acquired septicaemias were associated with endocarditis; half of these were with viridans streptococci, usually in patients with rheumatic heart disease, and 40% were in drug addicts with methicillin-sensitive Staphylococcus aureus. The commonest organisms causing community-acquired childhood infections were Salmonella spp. (27%) and Streptococcus pneumoniae (22%), whereas pneumococci accounted for only 3% of adult community-acquired micro-organisms. Haemophilus influenzae infections were uncommon and there was no case of meningococcal or gonococcal septicaemia. The commonest cause of hospital-acquired septicaemia was Staph. aureus (24%), of which 46% were methicillin-resistant. The characteristics of septicaemia in Hong Kong are influenced by the patient population structure, endemic disease patterns, local medical practice and socio-economic factors, but the rarity of Str. pneumoniae in adults and of H. influenzae and Neisseria meningitidis in children is unexplained.
A chemical marker of bacterial meningitis was sought by comparing derivatives of sterile cerebrospinal fluid (CSF) with cultures of organisms in spinal fluid and artificial media. The technique of gas chromatography-mass spectrometry with selected ion monitoring (GC-MS-SIM) was used, optimised for the analysis of fatty acids. Twenty candidate ions were screened, and an ion of mass: charge ratio (m/e) 268 was chosen for detection in clinical specimens. The origin of this marker is unknown, but it is probably the molecular ion of a C16:1 fatty acid. In 135 clinical specimens of CSF examined, the m/e 268 ion was found to be a useful marker for the common organisms that cause bacterial meningitis, giving a sensitivity of 88% and a specificity of 98%. The method was more rapid and more sensitive than conventional microscopy and culture, but CSF containing coagulase-negative staphylococci, Mycobacterium tuberculosis, Cryptococcus neoformans and some other uncommon pathogens gave inconsistent results. Many organisms produced characteristic ion profiles with multiple-ion monitoring, and this method of chemical analysis holds promise for the rapid diagnosis of bacterial infections to genus or species level.
Over five years the Bactec radiometric blood culture method yielded Salmonella typhi in 41 of 45 confirmed cases of typhoid fever, 90% of which were from the first culture set taken. Blood clot culture was positive in 18 (41%) of 44 confirmed cases and stool culture in 24 (59%) of 41. The yield from 2189 Widal clot cultures was only 0.03%. There were 68 positive results in 2258 unpaired Widal tests: 23 of them were falsely positive and 13 falsely negative, but in 11 out of 68 cases the Widal was the only positive laboratory test. It is concluded that routine clot culture is not cost effective if a sensitive blood culture method is used, and that the Widal test is useful only in selected patients.
The Cathra system is a commercial multipoint inoculation method for the identification of aerobic Gram negative bacteria. The system uses a replicator technique in which 21 different agar media can be inoculated simultaneously with 36 organisms. Identifications are made by use of a special computer database. The performance of this system was compared with that of the API 20E for the identification of 372 clinical isolates of Enterobacteriaceae and 133 miscellaneous Gram negative bacteria. For enterobacteria, the Cathra system was in 97% agreement with API 20E at species level and 98% at genus level. For miscellaneous Gram negative strains the two systems were in 59% agreement at species level and 77% at genus level. The Cathra system is suitable for use in diagnostic laboratories, especially those with a heavy workload and a wish to use break-point sensitivity testing. The identification database for miscellaneous Gram negative organisms, however, needs to be expanded.