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Infections of Rhodococcus equi, a well-known pathogen in animals which causes cavitated pneumonia similar to that caused by mycobacteria, were studied in three HIV-infected patients. This microorganism was isolated in the bronchoalveolar washings of two patients and in the sputum of the third. In two patients, Rh. equi represented the first clinical opportunistic manifestation of HIV disease. One patient died of concomitant Pneumocystis infection. The eradication of the microorganism occurred in two out of three patients. It was found that no isolates were resistant to erythromycin, claritromycin, rifampin, vancomycin, teicoplanin, imipenem, gentamycin or azithromycin (MIC values < or = 0.1 microgram/ml). Moreover, the quinolones (ciprofloxacin and ofloxacin) were found to be less effective, whereas neither the beta-lactam antibiotics nor chloramphenicol were effective therapy for this microrganism. At least two antimicrobial agents should be given contemporaneously to treat these infections for a period of up to several months. Our results suggest that the combinations erythromycin + rifampin or imipenem + teicoplanin are the most effective treatments in Rh. equi infections.
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PMID:Infections due to Rhodococcus equi in three HIV-infected patients: microbiological findings and antibiotic susceptibility. 767 72

Spirochaetal infections have been successfully treated with penicillin; more recently, erythromycin has been used in cases with known penicillin allergy. The discovery of the spirochaete Borrelia burgdorferi and the elaboration of a new generation of macrolides with properties that differ from older macrolides have led to new ways of treating spirochaetal disease with these compounds. This paper presents data on the in vitro and in vivo efficacy of a combination of roxithromycin and co-trimoxazole against B. burgdorferi. In vitro (checkerboard technique; B. burgdorferi strain B31; modified BSK II medium) it was found that while roxithromycin showed excellent efficacy against B. burgdorferi (MIC 0.031 mg/l), co-trimoxazole had no effect. However, the combination of both chemotherapeutics led to a minor synergistic effect, decreasing the MIC for roxithromycin by one dilution step at concentrations of co-trimoxazole from 256 to 8 mg/l. In addition, a clearly reduced growth of microorganisms was seen at concentrations of roxithromycin as low as 0.015 mg/l in combination with 256 to 4 mg/l co-trimoxazole, when compared to the positive controls. Most interestingly, however, the motility of B. burgdorferi was markedly reduced even when the two drugs were combined at very low concentrations. In an in vivo, non-randomised, open, prospective pilot study it was found that of 17 patients with confirmed late Lyme borreliosis (stage II/III), treated with combined roxithromycin (300 mg b.i.d.) and co-trimoxazole for 5 weeks, 13 (76%) recovered completely by the end of treatment, and four continued to have symptoms on follow-up at 6 and 12 months. This success rate is similar to that seen with i.v. penicillin and ceftriaxone. It appears that the reduced motility of B. burgdorferi makes the pathogen more accessible to the immune system.
Infection 1995
PMID:Roxithromycin in the treatment of Lyme disease--update and perspectives. 778 15

The increasing emergence of penicillin-resistant (Pr) strains of Streptococcus pneumoniae could pose a therapeutic problem in the next few years. Ceftriaxone (CRO), a broad-spectrum cephalosporin, exhibits a smaller increase in MICs against Pr S. pneumoniae strains than amoxicillin (AMO) (usually referred as to the "gold standard" therapy for pneumococcal infections). Therefore, we compared their respective efficacies in a leukopenic Swiss mouse model of pneumococcal pneumonia. Infection was induced with two serotype 19 strains: a penicillin-susceptible (Ps) strain (MICs of < 0.01 for penicillin, 0.03 for AMO, and 0.03 for CRO) and a Pr strain (MICs of 4 for penicillin, 2 for AMO, and 0.5 for CRO). Untreated mice died within 2 or 3 days. Against the Ps strain, the minimal protective dose (two subcutaneous injections at 12-h intervals for 3 days) for both CRO and AMO was 5 mg/kg of body weight (87% survivors). Ten-fold-increased doses of CRO (50 mg/kg) gave similar protection (75% survivors) against the Pr strain, whereas 20- and 40-fold-increased doses of AMO protected 0 and 34% of the animals, respectively, against the Ps strain. CRO had a marked and prolonged antibacterial effect in the lungs (2.7-log-unit reduction of CFU in 24 h after a single 50-mg/kg injection) against the Pr strain in comparison with AMO. A standard dosage of 50 mg of CRO per kg in mice resulted in peak levels in serum and protein binding comparable to those observed with 1 g given intravenously in humans. This dosage remained effective against a highly Pr S. pneumoniae strain in this model. The microbiological activity and pharmacodynamic and pharmacokinetic properties of CRO (time during which concentrations exceed the MIC for the test pathogen [delta t MIC], > or less than 8 h; and peak/MIC ratio, >90 for free active drug) accounted for its efficacy relative to AMO (50 mg/kg: delta t MIC, <2; peak/MIC ratio, <25) against the highly Pr S. pneumoniae strain used in this study.
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PMID:In vivo efficacy of a broad-spectrum cephalosporin, ceftriaxone, against penicillin-susceptible and -resistant strains of Streptococcus pneumoniae in a mouse pneumonia model. 781 Oct 3

Penicillin resistance occurred soon after the discovery of penicillin, first in the test tube and subsequently in patients. The prevalence of invasive pneumococcal disease has been estimated to be as high as 15-18/100,000 in the elderly population and even higher in AIDS patients, children and the very old. While prevention with pneumococcal vaccine seems the most reasonable solution, under-utilization of the vaccine and an increase in the number of immuno-compromised individuals has limited the success of this approach. Streptococcus pneumoniae is conventionally classified as penicillin-susceptible (MIC < 0.125 mg/l), penicillin-intermediate (MIC 0.125-1.0 mg/l) and penicillin-resistant (MIC > or = 2 mg/l). In many countries, penicillin resistance in pneumococci is on the increase and in some areas penicillin intermediate and resistant isolates reach 60%. As a consequence, a switch of therapy from penicillin to other agents is mandatory in infections caused by penicillin-resistant strains. Benzyl-penicillin, however, can be used for most infections caused by penicillin-intermediate and all infections caused by penicillin-sensitive strains. Third generation cephalosporins, and in particular cefotaxime, are an optional alternative, particularly in view of their low MICs against penicillin-susceptible and -intermediate and some penicillin-resistant strains, and the easily achievable therapeutic concentrations in serum, pulmonary tissues and other compartments in which pneumococcal infections occur. Third generation cephalosporins have a high safety record and can be administered to children, pregnant women and the elderly.(ABSTRACT TRUNCATED AT 250 WORDS)
Infection 1994
PMID:Treatment of severe infections caused by penicillin-resistant pneumococci. Role of third generation cephalosporins. 784 25

Escherichia coli strains (n = 678 and n = 670) isolated from faecal samples from 90 and 93 healthy volunteers of two cities, Weert and Roermond respectively, were analysed for their susceptibility to 12 antimicrobial agents during a 15-week period. Significant differences between both cities in the distribution of the MIC values were observed for apramycin, chloramphenicol, kanamycin, neomycin, nitrofurantoin, sulfamethoxazole and trimethoprim. For Weert (n = 678) the antibiotic resistance percentages varied from 0.4% for nalidixic acid to 26.7% for sulfamethoxazole. For Roermond (n = 670) the figures varied from 0.6% for nitrofurantoin to 37.5% for sulfamethoxazole. Resistance to amoxicillin/clavulanate was not found in either city. The most frequent pattern was resistance to sulfamethoxazole only, followed by resistance to oxytetracycline, streptomycin and sulfamethoxazole. In each individual there was only a small variation in resistance patterns of the isolates, i.e. the majority had one (n = 51) or two (n = 63) patterns with a maximum of five during the 15-week period. A fully susceptible pattern was found in the strains from 38 individuals.
Infection
PMID:Carriage of antibiotic-resistant Escherichia coli by healthy volunteers during a 15-week period. 792 14

In 1990-1991, in a national surveillance study of bacterial resistance, ciprofloxacin data from geographic and demographically diverse institutions were collected. Most of the isolates were from hospitalized patients. Ciprofloxacin susceptibility was obtained on 154,689 clinical isolates comprising 48 genera and 128 species or groups; 60.2% of the species or groups and 62.3% of the isolates were gram-negative. MIC tests and identification tests also were performed on 12,012 of these isolates, which had been submitted to our in-house laboratory. For all surveillance isolates, 88.2% were susceptible, 4.6% were moderately susceptible, and 7.2% were resistant to ciprofloxacin. Most isolates (96.2%) of the surveillance Enterobacteriaceae were susceptible to ciprofloxacin, as were 87.7% of the Pseudomonas aeruginosa (7.8% resistant). A majority of the methicillin-susceptible strains of Staphylococcus aureus were susceptible (95.7%) or moderately susceptible (1.4%) to ciprofloxacin. But a majority of methicillin-resistant isolates were resistant (76.4%) to ciprofloxacin. Most of the pneumococci (96.5%) were susceptible or moderately susceptible to ciprofloxacin with 92.7% of these isolates having MICs of 1 mg/l (susceptible) or 2 mg/l (moderately susceptible). The ciprofloxacin data for the isolates tested in our in-house laboratory generally confirmed the susceptibility rates of those from the surveillance data. This study shows that, with the exception of methicillin-resistant staphylococci, ciprofloxacin has retained a high level of activity against most bacterial pathogens.
Infection 1994
PMID:Susceptibility of clinical bacterial isolates to ciprofloxacin in the United States. 792 35

Resistance to fluoroquinolone antibacterials has emerged in a limited form, largely amongst certain specific species and often restricted to single clones of these pathogens. Mediated by chromosomal mutation, the major mechanisms are alterations in gyrase subunits and reduced penetration associated with decreased outer membrane protein production. Resistance is most commonly seen to emerge amongst pathogens with higher than average initial MICs, particularly affected species being Pseudomonas aeruginosa and the staphylococci. Resistance is more likely to be encountered when such pathogens are exposed to concentrations at or below the MIC, which may result either from underdosage, the presence of the organism in a sequestered site, e.g. bone or prostate, or from confounding factors such as the presence of pus, indwelling prostheses or interactions which reduce absorption from the gastrointestinal tract. Repetitive use of these agents and continued use of fluoroquinolone precursors, such as nalidixic acid, may also contribute to resistance emergence. Most resistance is appearing amongst hospitalised patients and much of the apparent burden reflects horizontal cross-infection of many patients by a single resistant clone. There is very limited data linking increasing community use of fluoroquinolones with resistance emergence amongst pathogens such as Escherichia coli. In the main, the emergence of resistance can be anticipated and perhaps prevented or avoided for the sorts of risk groups and pathogens described. The use of adequate dosage by appropriate routes of administration in suitable patients and implementation of surveillance procedures for those at risk will minimise such problems. Policies for the effective use of these valuable agents should be part of everyday practice in hospitals.
Infection 1994
PMID:Bacterial resistance to fluoroquinolones: lessons to be learned. 792 33

The profile of antibacterial activity of cefpirome was compared with that of nine other antimicrobial agents against 513 gram-negative bacteria isolated from septicemic patients. All strains were evaluated for their sensitivity by disc diffusion and broth dilution tests (MIC and MBC). Cefpirome was compared to cefazolin, cefuroxime, ceftazidime, ceftriaxone, aztreonam, imipenem, ticarcillin, tobramycin and ciprofloxacin. Among the five cephalosporins tested in this study, cefpirome was the most active against all isolates. The MIC50 and MIC90 of eight isolates of Acinetobacter calcoaceticus were 2 and 4 mg/l and those of 89 Pseudomonas aeruginosa were 2 and 8 mg/l, respectively. The MIC90 values of cefpirome for all other groups of bacteria were < or = 1 mg/l. The activity of cefpirome against gram-negative bacteria is at least as good as that of aztreonam and imipenem. The only drug showing a better profile of activity than cefpirome is ciprofloxacin. The scattergram of the 513 isolates for cefpirome MICs and inhibitory zones with the 30 micrograms disc, showed that only eight isolates were not susceptible to cefpirome. These data suggest that the in vitro activity of cefpirome is comparable to if not better than that of other beta-lactams and tobramycin.
Infection
PMID:Bactericidal activity of cefpirome (HR 810) against 513 gram-negative bacteria isolated from blood of septicemic patients. 800 94

In an open-label controlled study 23 HIV-infected patients (CDC IV A-E) with documented oropharyngeal candidosis were treated with 100 mg fluconazole orally over 5 days (53 episodes; 1-6 treatments/patient). Efficacy data were compared with a control group of 21 patients who received treatment for 10-21 days with 100 mg fluconazole for candidosis. Candida isolates were repeatedly recovered from patients before and after treatment with fluconazole and antifungal susceptibility testing (microbroth-dilution) was done. Inoculum size, medium pH, incubation time and temperature were standardized. Up to 85% of patients responded to therapy clinically and mycologically. Candida albicans was the most important yeast (86%) isolated from cultures of oral washings. In 90% of C. albicans isolates MIC to fluconazole were low (< or = 1.56 mg/l). Primary resistance to fluconazole was not seen, but secondary resistance occurred in two cases clinically and in vitro (MIC > or = 25 mg/l). Short treatment for 5 days was as successful as for 10 to 21 days without leading to significantly more recurrences of oral candidosis in these patients. Selection of Candida spp. other than C. albicans (e.g. Candida krusei, Torulopsis glabrata) under repeated fluconazole treatment occurred rarely. One patient developed clinical signs of chronic recurrent candidiasis, where only C. krusei could be cultured repeatedly.
Infection
PMID:Correlation between antifungal susceptibility testing of Candida isolates from patients with HIV infection and clinical results after treatment with fluconazole. 807 Sep 27

The question of whether ampicillin and sulbactam are able to penetrate sufficiently into costal cartilage tissue was investigated in 21 children undergoing surgery for funnel chest malformations. The concentrations of both compounds were determined in the core and mantle pieces of samples taken 45 min or 120 min after infusion of ampicillin/sulbactam (33.3/16.7 mg/kg bodyweight) preoperatively for antibiotic prophylaxis. Ampicillin was determined by bioassay and sulbactam was determined by gas-chromatography/mass spectrometry. Mean concentrations of ampicillin were 23.3 mg/kg and 10.4 mg/kg at 45 min and at 27.4 mg/kg and 7.8 mg/kg 120 min in the mantle and core piece, respectively. Mean concentrations of sulbactam were at the same time 21.3 mg/kg and 9.7 mg/kg and 17.5 mg/kg and 11.9 mg/kg, respectively. These values indicate that both compounds achieve high concentrations even in bradytrophic tissue such as cartilage. The concentrations exceed the MIC values of important bacterial pathogens involved in postoperative wound infections. Therefore ampicillin protected by sulbactam appears to be a well-suited agent for perioperative prophylaxis in thoracic surgery.
Infection
PMID:Penetration of ampicillin and sulbactam into human costal cartilage. 807 Sep 30


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