Mucormycosis during deferoxamine therapy is a siderophore-mediated infection. In vitro and in vivo animal studies.

This study investigates the pathophysiology of mucormycosis caused by Rhizopus, which has been reported in 46 dialysis patients, while treated with deferoxamine (DFO). This drug aggravates mucormycosis, which we experimentally induced in guinea pigs and which lead to a shortened animal survival (P < or = 0.01). The drug's effect on Rhizopus is not mediated through the polymorphonuclear cells. Fe.DFO, the iron chelate of DFO, abolishes the fungistatic effect of serum on Rhizopus and increases the in vitro growth of the fungus (P < or = 0.0001). This effect is present at Fe.DFO concentrations > or = 0.01 microM, at which fungal uptake of radioiron from 55Fe.DFO is observed. A 1,000-fold higher concentration of iron citrate is required to achieve a similar rate of radioiron uptake and of in vitro growth stimulation as observed with Fe.DFO. These in vitro effects of Fe.DFO (1 microM) in serum on radioiron uptake and on growth stimulation are more striking for Rhizopus than for Aspergillus fumigatus and are practically absent for Candida albicans. For these three fungal species, the rates of radioiron uptake from 55Fe.DFO and of growth stimulation in the presence of Fe.DFO in serum are directly related (r = 0.886). These results underscore the major role of Fe.DFO in the pathogenesis of DFO-related mucormycosis. Pharmacokinetic changes in uremia lead to a prolonged accumulation of Fe.DFO after DFO administration, which helps explain the increased sensitivity of dialysis patients to DFO-related mucormycosis.

Surveillance of aminoglycoside resistance. European data.

The susceptibility patterns of gram-negative aerobic organisms to aminoglycosides differ widely from one European health care center to another and depend upon local antibiotic prescribing policies. Reports of the susceptibility of Pseudomonas aeruginosa to gentamicin and tobramycin have ranged from as low as 49.8 percent and 77.7 percent, respectively, in Greece, to as high as 96.6 percent and 99.2 percent, respectively, in the United Kingdom. The susceptibility of P. aeruginosa to gentamicin, tobramycin, and amikacin decreased in our hospital from 73.1 percent, 94.8 percent, and 95.6 percent, respectively, in 1982, to 43.1 percent, 70.6 percent, and 74.3 percent, respectively, in 1984. A prospective surveillance study of the susceptibility of gram-negative aerobic bacilli to four aminoglycosides (gentamicin, tobramycin, amikacin, and netilmicin) was performed over a period of 17 months. Gentamicin and tobramycin were freely used, while the use of amikacin was restricted throughout the hospital during a four-month baseline period (May through August 1984). Gentamicin and tobramycin accounted for 94 percent of the aminoglycoside use. During the following 13 months (September 1984 through September 1985), amikacin was used as the first-line aminoglycoside and accounted for more than 97 percent of the aminoglycoside usage. A total of 1,866 organisms were analyzed during the baseline period; 5,429 were analyzed during the amikacin-usage period. The overall susceptibility to gentamicin, tobramycin, amikacin, and netilmicin increased from 86.9 percent, 90.4 percent, 94.2 percent, and 88.3 percent, respectively, to 92.3 percent, 94.0 percent, 97.3 percent, and 92.3 percent, respectively. P. aeruginosa isolates had the most striking changes, with the susceptibility to gentamicin, tobramycin, amikacin, and netilmicin increasing from 43.1 percent, 70.6 percent, 74.3 percent, and 50.6 percent, respectively, during the baseline period, to 64.5 percent, 81.6 percent, 90.8 percent, and 65.1 percent, respectively, during the amikacin-usage period. The use of amikacin as a first-line aminoglycoside, while use of the other aminoglycosides was restricted, seemed to have a favorable influence on the susceptibility pattern of gram-negative aerobic isolates in our hospital.

Temocillin in the treatment of gram-negative septicaemia.

The effectiveness of temocillin in the treatment of culture-proven Gram-negative septicaemia was investigated in 22 adult patients, most of whom were elderly with serious underlying diseases. Administration of temocillin 2g twice daily to 15 patients or 1g twice daily to 7 patients resulted in clinical cure in 15 patients (68%), while 4 responded partially (18%) and 3 were considered failures (14%). The original pathogen was eradicated from 20 of 21 assessable patients (95%), 1 patient was unassessable and 1 was considered a failure. Superinfection was documented in 4 patients, originating twice in a central venous catheter, once in the urinary tract and once in an unidentified source. No clinical nor biological side effects were observed except for pain at the injection site in 1 patient who received the drug intramuscularly. We conclude that temocillin in monotherapy can be used effectively for proven Gram-negative septicaemia, and that the safety of the drug makes it particularly valuable in the elderly.

In vitro activity of temocillin against clinical isolates.

The minimum inhibitory concentrations of temocillin against more than 1000 clinical isolates were determined by an agar dilution method. Temocillin showed excellent activity against Haemophilus influenzae, pathogenic Neisseria species and Branhamella catarrhalis, including beta-lactamase producing strains, but showed very low activity or was inactive against Gram-positive cocci and Campylobacter, Bacteroides, Acinetobacter and Pseudomonas species. Good activity was obtained against 702 Enterobacteriaceae, including isolates resistant to the other penicillins and first- and second-generation cephalosporins, with 92% of all the strains inhibited at a concentration of 8 mg/L. However, the most striking property of temocillin was its high beta-lactamase stability which resulted in both a very narrow range of MICs within which all the isolates were inhibited, and a small influence of inoculum size on the MICs.

Effect of renal function and dialysis on temocillin pharmacokinetics.

Temocillin pharmacokinetics in renal impairment were investigated following an intravenous bolus injection of 15 mg/kg. The 28 patients were divided into 5 groups of varying renal function, from normal to uraemic [including a group being treated with haemodialysis and a group on continuous ambulatory peritoneal dialysis (CAPD)]. The distribution of temocillin into the tissues was not affected by renal dysfunction. Uraemia as compared to normal renal function resulted in a 4.3-fold decrease in temocillin clearance and a 3.1-fold decrease in urinary recovery over 24 hours, as well as a 5- and 3.7-fold increase in the beta half-life and the area under the curve (AUC), respectively. Haemodialysis doubled the serum clearance and halved the beta half-life of temocillin in the uraemic subject, but CAPD over 24 hours eliminated only 8% of the temocillin dose, resulting in a minimal change in pharmacokinetics. Temocillin dosage adjustments in renal failure are proposed.

Nasal and cutaneous carriage of Staphylococcus aureus in hemodialysis patients: the effect of nasal mupirocin.

Fifteen of 20 hemodialysis patients who carried Staphylococcus aureus in their nares also carried the organism on their hands; 2 of 20 patients who did not carry S aureus in their nares carried S aureus on their hands (P < .001). Eighty-seven percent of patients who carried S aureus in their nares and on their hands carried the same strain at both sites. Intranasal mupirocin eliminated S aureus from both sites.

Epidemiology of Staphylococcus aureus infections in patients on hemodialysis.

OBJECTIVE: To determine the epidemiology of Staphylococcus aureus infections in hemodialysis patients. METHOD: S aureus isolates from surveillance cultures and from sites of infection were evaluated by both bacteriophage typing and restriction endonuclease digestion of plasmid DNA. SETTING: A hemodialysis unit in Brugge, Belgium. ORGANISMS: S aureus isolates from 11 chronic hemodialysis patients who had participated in the placebo arm of a previously reported placebo-mupirocin comparative study. RESULTS: Of 75 S aureus isolates evaluated, 63 were from cultures of nares and 12 from infections (three arteriovenous fistula infections, four wound infections, and five bacteremias). All isolates were typed by bacteriophages and 56 (75%) had plasmids. Three patients developed 12 infections. Eleven infections were caused by isolates previously identified in surveillance cultures. Only one infection was caused by a strain not identified previously in surveillance cultures. CONCLUSION: These results support the hypothesis that S aureus isolates causing infections in hemodialysis patients are of endogenous origin.

Recurrent bacteremia by Chryseobacterium indologenes in an oncology patient with a totally implanted intravascular device.

Chryseobacterium indologenes was isolated from the blood cultures of an oncological patient with a totally implantable device. Because a catheter-related infection was suspected, the Port-A-Cath was removed after a 10-day course of piperacillin-tazobactam. Differences in susceptibility may exist if either the criteria for either Pseudomonas or Enterobacteriaceae are used.

The use of nasal mupirocin ointment to prevent Staphylococcus aureus bacteraemias in haemodialysis patients: an analysis of cost-effectiveness.

Nasal carriage of Staphylococcus aureus is a risk factor for the development of infections caused by S. aureus in haemodialysis patients. This study compared the incidence of bacteraemia caused by S. aureus during 6 months of use of nasal 2% calcium mupirocin ('Nasal Bactroban') 3-times a week for nasal carriers with the incidence observed previously in the same dialysis unit without the use of mupirocin. Nasal mupirocin led to the total eradication of nasal carriage of S. aureus, a 4.26-fold reduction in the incidence of S. aureus bacteraemia, and a substantial cost saving. After a cumulative experience of nasal mupirocin in haemodialysis patients of more than 43 patient-years, the development of mupirocin resistance was not observed.

Staphylococcus aureus infections in haemodialysis patients: pathophysiology and use of nasal mupirocin for prevention.

Staphylococcus aureus is the most frequently (42%) isolated micro-organism during bacteraemic episodes in haemodialysis patients. Nasal carriage of S. aureus is of major importance in determining the risk of subsequent infections. Indeed, nasal carriage of S. aureus is highly prevalent in uraemic patients from the onset of maintenance dialysis therapy. The strains isolated simultaneously from the nares and the hands are usually the same. Likewise, infecting S. aureus strains and those isolated from nasal surveillance cultures obtained in the same patient are usually similar. S. aureus infections in haemodialysis patients are thus mostly to be considered as auto-infections. The nares are therefore an elective site for the prevention of S. aureus infections in haemodialysis patients. This has been demonstrated with oral rifampin, and more recently with nasal mupirocin, which is highly effective. Long-term application of nasal mupirocin (e.g. once per week) is cost-effective and is only rarely associated with the emergence of mupirocin-resistance in S. aureus.

In vitro of cefotaxime against cephalothin-resistant clinical isolates.

Cefotaxime is more active than six other cephalosporins against 150 cephalothin-resistant Enterobacteriaceae strains and is the only drug which is more active than ampicillin against Haemophilus. It shows a potentially useful activity against Pseudomonas.

A blood-free medium for isolation of thermophilic Campylobacter species.

A blood-free medium for the recovery of thermophilic Campylobacter was compared with Butzler Medium Virion during a one-year study using 2,893 human feces samples. Ninety Campylobacter strains (3.1%) were isolated after incubation for 48 h at 42 degrees C in a candle jar atmosphere. Three strains of Campylobacter jejuni were isolated on the blood-free medium only and one on Butzler Medium Virion only. Fecal flora was equally well inhibited on both media except for gram-positive organisms, which were completely inhibited only on the blood-free medium.

In vitro susceptibility of Capnocytophaga species to 29 antimicrobial agents.

A hemoglobin-supplemented medium composed of Columbia agar base supplemented with 1% hemoglobin and 1% Polyvitex was used to investigate the in vitro activity of 29 antimicrobial agents against Capnocytophaga species. Clindamycin was the most active agent, with all strains being inhibited by 0.06 microgram/ml or less. Amoxicillin-clavulanic acid and imipenem were the most active among the beta-lactam antibiotics (MIC for 90% of strains tested [MIC90], 0.50 microgram/ml); other very active drugs were BMY 28142, cefpirome, cefotaxime, ceftazidime, and ceftriaxone (MIC90, 0.06 to 0.50 micrograms/ml), although at least one strain showed resistance to each of these antibiotics (MIC, greater than or equal to 16 micrograms/ml). Ciprofloxacin was the most active among the quinolones, with all strains being inhibited by 0.50 microgram/ml. The MICs of the other four drugs ranged from 0.12 to 4 micrograms/ml. Ampicillin, penicillin G, ticarcillin, aztreonam, and temocillin were moderately active (MIC90, 1 to 8 micrograms/ml; MIC range, less than or equal to 0.03 to greater than 128 micrograms/ml). All strains were uniformly resistant to the aminoglycosides, polymyxin B, vancomycin, trimethoprim, and amphotericin B. Three strains produced beta-lactamase. No significant difference was found between the susceptibility of strains isolated from various sources or patients.

Pharmacokinetic evaluation of ofloxacin in serum and tonsils.

The bioavailability of ofloxacin in tonsil tissue, after a single oral dose of 200 mg 2 h before surgery, was evaluated in 14 patients undergoing tonsillectomy for recurrent or chronic infection. A blood specimen was obtained just before drug administration and at the time of tonsillectomy, together with a specimen of tonsil tissue. The mean values of the serum and tonsil concentrations 2 h after a single dose of 200 mg were 1.17 mg/l +/- 0.47 and 1.61 mg/l +/- 0.62 respectively with a mean tonsil/serum ratio of 1.40 +/- 0.19. These values indicate good penetration of ofloxacin into tonsil tissue. No clinical or biological side-effects were observed.

The importance of the quinolones in antibacterial therapy.

New quinolones have obtained a definite position in the treatment of certain sexually transmitted diseases, urinary tract infections, prostatitis, gastrointestinal infections, nosocomially acquired pulmonary infections with resistant organisms, pseudomonas infections in cystic fibrosis, and osteomyelitis. The role of the new quinolones in upper respiratory tract infections, acute or chronic bronchitis and community acquired pneumonia is far less established. Their role in selective decontamination of the gastrointestinal tract in neutropenic patients is under investigation. Future modifications may increase their usefulness for treatment of mycobacterial infections, chlamydial infections, and mycoplasma and ureaplasma infections. The structural relationship of the new quinolones with antimalarial drugs may open new perspectives for the treatment of falciparum malaria.

Comparison of three rapid methods, tributyrine, 4-methylumbelliferyl butyrate, and indoxyl acetate, for rapid identification of Moraxella catarrhalis.

Moraxella catarrhalis can easily be differentiated from other oxidase-positive, gram-negative cocci with tributyrine, 4-methylumbelliferyl butyrate, or indoxyl acetate. All M. catarrhalis give positive reactions, and all Neisseria spp. give negative reactions. The 4-methylumbelliferyl butyrate tube test and indoxyl acetate strip test provide same-day identification of M. catarrhalis isolates.

Multiple dose pharmacokinetics of intravenous acyclovir in patients on continuous ambulatory peritoneal dialysis.

Once daily 60 min iv infusions of acyclovir at 2.5 mg/kg were administered to six uraemic patients (three male, three female of mean age 52 years and body weight 60 kg) treated by continuous ambulatory peritoneal dialysis (CAPD). Blood and dialysate samples were taken for analysis of acyclovir by radio-immunoassay. A three-compartment pharmacokinetic model was found necessary to explain the profiles obtained. Steady-state was reached by the third day, with little change in mean peak or trough plasma levels between day one (25 and 3 microM) and day five (29 and 4 microM). Mean total plasma clearance was 46 ml/h/kg, of which 12% was due to peritoneal dialysis. The model parameters predicted efficient transfer of acyclovir from the peritoneum to plasma, such that hypothetical peritoneal dosing might give 91% bioavailability. In patients treated by CAPD, iv acyclovir should be administered at 2.5 mg/kg/day.