Emergence of ciprofloxacin resistance during treatment of Salmonella osteomyelitis in three patients with sickle cell disease.

The treatment of salmonella osteomyelitis in sickle cell disease (SCD) is difficult and the emergence of antibiotic resistance in Salmonella spp presents further problems for clinicians treating SCD. Three patients presented with salmonella bacteraemia. Treatment with several intravenous antibiotics did not prevent the subsequent development of osteomyelitis. Emergence of resistance to multiple antibiotics, including ciprofloxacin, during the treatment of salmonella osteomyelitis in SCD patients is reported here for the first time. Ceftriaxone 2 g once daily given for 3 months to 3 years was an effective and convenient treatment for osteomyelitis caused by multiply-resistant salmonella. Two of these patients gave a definite history of diarrhoea, and stool cultures confirmed the presence of Salmonella spp in one. Our experience shows that salmonella osteomyelitis may not be prevented by early treatment of bacteraemia in SCD patients. Other measures to reduce the risk of salmonella infection are therefore necessary.

Activity of sucralfate (sucrose octa-sulphate), an anti-ulcer agent, against opportunistic gram-negative bacilli.

The in-vitro activity of sucralfate (sucrose octa-sulphate) in suspension was examined against 128 strains of Gram-negative bacilli. Inhibitory activity was demonstrated against all isolates and bactericidal activity was demonstrated for 68. Sucralfate has inhibitory and bactericidal antibacterial activity which may contribute to its in-vivo clinical efficacy.

Epidemiology, bacteriology and control of an outbreak of Nocardia asteroides infection on a liver unit.

An outbreak of Nocardia asteroides infection affecting seven patients is described. Over a 5-week period, five patients with liver disease admitted to a ward developed clinical and laboratory evidence of nocardiosis, and two further cases were diagnosed 3 and 5 months later. Three out of the five patients who received specific antimicrobial therapy responded to treatment; in three patients nocardia infection was considered to have contributed to death. In six out of the seven patients, nocardiosis followed immunosuppression. A common-source outbreak was considered to be responsible for infection in the first five patients. In two patients, presentation of infection 5 and 7 months after the first case may have been due to prolonged colonization or subclinical infection with Nocardia. Biotyping of the seven isolates using a fluorogenic biochemical method identified three distinct strains of N. asteroides. The most probable source of Nocardia was contaminated brick and plaster dust arising from building work in an area adjacent to the ward. However, samples of air, dust and water failed to yield N. asteroides. Infection control measures included ward closure followed by thorough cleaning, and formaldehyde fumigation.

The in-vitro activity of ceftibuten against 475 clinical isolates of gram-negative bacilli, compared with cefuroxime and cefadroxil.

The in-vitro activity of ceftibuten was compared with cefuroxime and cefadroxil against 475 clinically-significant, epidemiologically-distinct isolates of Gram-negative bacilli: 170 from blood, 212 from urine and 93 from a supplementary collection of multiply-resistant strains known to have resistance plasmids, to have caused sporadic or epidemic nosocomial infection, or both. Ceftibuten MICs ranged from 0.003 to greater than 32 mg/l, with a modal MIC of 0.01 mg/l: 95% of all isolates had ceftibuten MIC values of less than or equal to 8 mg/l, the sensitivity breakpoint suggested by the manufacturer. Ninety per cent of isolates had MICs of less than or equal to 1 mg/l and 49% had MICs of less than or equal to 0.03 mg/l. All isolates of Klebsiella, Serratia, Proteus and Providencia spp., and Morganella morganii had MIC values of 8 mg/l or less. Only two of 124 isolates of Escherichia coli tested, and only one of 23 Citrobacter spp., had MICs of greater than 8 mg/l (16, 16 and greater than 32 mg/l respectively). Resistance MIC greater than 16 mg/l) was more frequent among Enterobacter and Acinetobacter spp. Thirteen of 52 Enterobacter spp., and seven of 18 Acinetobacter calcoaceticus had MICs of at least 32 mg/l. MIC ranges, modal MICs and MIC90s indicated that ceftibuten was, with the exception of only two strains, consistently more active in-vitro than cefuroxime, which was in turn more active than cefadroxil.

The in-vitro activity of cefadroxil, and the interpretation of disc-susceptibility testing.

Minimum inhibitory concentrations (MICs) of cefadroxil were determined for 749 defined clinically-significant bacteria isolated in a London teaching hospital and for 63 strains from an international collection of Gram-negative bacilli. Assuming a breakpoint of 16 mg/l, for the hospital isolates 81.8% of Gram-negative bacilli and 83.4% of Gram-positive cocci were sensitive. No significant difference between in-patient, out-patient or community-acquired isolates was found. Ninety-five and a half per cent of Escherichia coli, Klebsiella aerogenes (including gentamicin-resistant strains), Proteus mirabilis, and (with the exception of Streptococcus faecalis and methicillin-resistant Staphylococcus aureus) all Gram-positive cocci were sensitive. Of 41 strains of Enterobacter spp., were resistant. Most indole-positive Proteus, and all Serratia and Acinetobacter spp. were resistant, including 36 additional strains taken from an international collection. Of 30 strains of Haemophilus influenzae, only six had MICs of 16 mg/l or less. For disc susceptibility testing, the standard disc containing 30 micrograms of cefadroxil reliably gave zones of greater than 17 mm for organisms with MICs of less than 16 mg/l. A zone of less than 14 mm corresponded to MICs of greater than 64 mg/l. Despite a lack of controlled clinical trials, the results of this study (taken with favourable pharmacokinetics) suggest that cefadroxil has potential as an oral cephalosporin in hospital practice in the U.K.

Ceftazidime in the treatment of serious Pseudomonas aeruginosa sepsis.

28 patients with serious Pseudomonas aeruginosa sepsis were enrolled into a prospective open study using ceftazidime (CAZ). 10 patients had rapidly fatal underlying pathology, including 5 neutropenic (neutrophils less than 1.0 X 10(9)/l) patients with malignancy. 9 patients including all those with neutropenia also received concomitant therapy with other active antipseudomonal antibiotics (mainly aminoglycosides). All isolates were initially sensitive to CAZ. A favourable response was seen in 18/27 (67%) evaluable cases. Genitourinary infection and osteomyelitis responded well with 100% and 83% favourable responses respectively. Soft tissue and respiratory tract infection responded less well. Results with biliary sepsis were disappointing (all 3 failed therapy). Of the 9 patients failing treatment 5 responded to alternative antibiotics (usually combination therapy of ureidopenicillin plus aminoglycoside). 2 died primarily from underlying pathology and 2 as a direct result of Ps. aeruginosa sepsis. Toxicity was minimal. In the few cases observed other agents and underlying pathology possibly contributed. The most disturbing feature of the study was the emergence of multiple beta-lactam resistance in organisms whilst treated with CAZ. 5 cases occurred, 4 in the infected strain and 1 in a superinfecting strain, occurring in 4 patients within 10 days of starting therapy. 2 cases occurred in patients receiving concomitant aminoglycosides.