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PubMed1979

Cefuroxime: a review of its antibacterial activity, pharmacological properties and therapeutic use.

Cefuroxime is a new semisynthetic cephalosporin for parenteral administration. It is resistant to destruction by beta-lactamases produced by staphylococci and most Gram-negative aerobic bacteria and is active against many bacteria resistant to cephalothin. Cefuroxime is the most active of the cephalosporins against gonococci and Haemophilus influenzae particularly against beta-lactamase producing strains. Given by intramuscular or intravenous injection cefuroxime is effective against a wide variety of infections caused by Gram-positive or Gram-negative aerobes, but has no effect against infections caused by Pseudomonas aeruginosa or B. fragilis. Cefuroxime is of value in the treatment of respiratory infections due to Haemophilus influenzae and Streptocococcus pneumoniae and is useful against cephalosporin-resistant Klebsiella and Enterobacter infections. Cefuroxime is an alternative to spectinomycin for the treatment of beta-lactamase producing Neisseria gonorrhoeae infections. It is generally well tolerated and appears not to be nephrotoxic when given alone at usual dosages.

Adult↗
PubMed1985

Norfloxacin. A review of its antibacterial activity, pharmacokinetic properties and therapeutic use.

Norfloxacin is one of the new 4-quinolone antibacterial agents. A fluorinated piperazinyl-substituted congener of nalidixic acid, it demonstrates a much wider in vitro antibacterial spectrum and greater potency than the parent compound. Its antibacterial activity against most Gram-negative pathogens is enhanced in comparison to nalidixic acid, but is similar to that of some of the other new 4-quinolones like enoxacin, and slightly less than that of ciprofloxacin. Unlike nalidixic acid, norfloxacin is also active against Pseudomonas aeruginosa and some Gram-positive organisms. In acute or uncomplicated urinary tract infections, norfloxacin has repeatedly been shown to be as effective as co-trimoxazole. Single studies have demonstrated a significantly better bacteriological cure rate with norfloxacin than with pipemidic acid, and similar cure rates with norfloxacin and both a nalidixic acid/sodium citrate mixture and amoxycillin. Similar results were found in a few studies comparing norfloxacin to pipemidic acid or amoxycillin in patients with chronic and/or complicated urinary tract infections. Norfloxacin is as effective as spectinomycin in gonorrhoea due to penicillin-resistant N. gonorrhoeae, and cures bacterial gastroenteritis caused by several gastrointestinal pathogens. Norfloxacin appears to be well tolerated and may have a low propensity to select for bacterial resistance during clinical use, although the latter needs further confirmation.

Antifungal Agents↗
PubMed1989

Sultamicillin. A review of its antibacterial activity, pharmacokinetic properties and therapeutic use.

Sultamicillin is the tosylate salt of the double ester of sulbactam plus ampicillin. Sulbactam is a semisynthetic beta-lactamase inhibitor which, in combination with ampicillin, extends the antibacterial activity of the latter to include some beta-lactamase-producing strains of bacteria that would otherwise be resistant. The combination of sulbactam plus ampicillin for parenteral use has previously been shown to be clinically and bacteriologically effective in a variety of infections. The chemical linkage of sulbactam and ampicillin has now produced an orally effective compound, sultamicillin, with antibacterial activity and clinical efficacy which are similar to those of the parenteral formulation. Sultamicillin has been shown to be clinically effective in non-comparative trials in patients with infections of the respiratory tract, ears, nose and throat, urinary tract, skin and soft tissues, as well as in obstetric and gynaecological infections, and in the treatment of gonorrhoea. In a small number of controlled trials, sultamicillin has shown comparable clinical efficacy to phenoxymethyl penicillin (penicillin V) and to amoxycillin (alone and in combination with clavulanic acid) in the treatment of paediatric streptococcal pharyngitis and acute otitis media, respectively; to cefaclor in the treatment of acute otitis media in adults; and to bacampicillin, cloxacillin and flucloxacillin plus ampicillin in skin and soft tissue infections in adults, children and adult diabetic patients, respectively. Sultamicillin was superior in efficacy to bacampicillin in the treatment of chronic respiratory infections, to cefaclor in the treatment of acute otitis media in adults, and to cefadroxil in the treatment of patients with complicated urinary tract infections. However, in single-dose treatment of uncomplicated gonorrhoea, sultamicillin (1500mg plus probenecid 1g) was inferior to a 2g intramuscular dose of spectinomycin. While in several studies the incidence of diarrhoea associated with sultamicillin was greater than that with comparative antibacterials, sultamicillin-associated diarrhoea was generally mild and transitory, although occasionally severe enough to necessitate discontinuation of treatment. Further studies in larger groups of patients are needed to clarify the therapeutic efficacy and safety of sultamicillin in comparison with other antibacterial regimens, and to determine the optimum single dosage for the treatment of gonorrhoea. Nonetheless, sultamicillin appears to provide a similar pharmacodynamic and pharmacokinetic profile to that of parenteral sulbactam plus ampicillin and, as such, will extend the therapeutic efficacy of ampicillin, with the further advantage of allowing treatment of patients with an oral formulation, thus avoiding the potentially adverse clinical and financial effects of prolonged parenteral therapy.

Ampicillin↗
PubMed2006

Development of a toxicogenomics in vitro assay for the efficient characterization of compounds.

In vitro toxicogenomics represents a useful approach for evaluating the toxic properties of new drug candidates early in the drug discovery process using minimal amounts of compounds. The aim of this study was to develop in vitro-based gene expression assays for two prototypical toxicological classes: aryl hydrocarbon receptor (AhR) agonists and peroxisome proliferator activated receptor alpha (PPAR alpha) agonists. Primary rat hepatocytes were exposed to a number of class-specific compounds, including 3-methylcholanthrene, aroclor, and beta-napthoflavone as AhR agonists, bezafibrate, clofibrate, and Wy-14643 as peroxisome proliferators, and chlorpheniramine, penicillin and spectinomycin as negative controls. Global gene expression profiles were generated with microarrays for each class of compounds. Using linear discriminant analysis coupled with permutation-based t-test, gene signatures were established to classify compounds according to a discriminant score. The final gene signatures consist of eight genes for AhR agonism and 11 genes for PPAR alpha agonism, and were further validated using additional compounds. The assay was initially developed using a microarray platform. The authors then evaluated whether it could be transferred to a more cost-effective platform with higher throughput. The results indicate that a small set of genes can be used to quantitatively assess the degree to which a compound falls into a certain mechanistic toxicological class. While this study only focused on two classes, it could be expanded to encompass other toxicological mechanistic classes as well. Furthermore, by adapting this type of assay to a higher throughput platform, in vitro toxicogenomics can represent an effective approach to generate robust toxicological data early in the drug discovery process.

Animals↗
PubMed2006

Evaluation of changes in antimicrobial susceptibility patterns of Pasteurella multocida subsp multocida isolates from pigs in Spain in 1987-1988 and 2003-2004.

OBJECTIVE: To determine the susceptibility of strains of Pasteurella multocida subsp multocida isolated from lung specimens of pigs with pneumonia to 20 antimicrobials and to evaluate the emergence of resistance to those antimicrobials in Spain during the past 2 decades. SAMPLE POPULATION: 63 isolates recovered from 1987 to 1988 and 132 isolates recovered from 2003 to 2004. PROCEDURE: A broth microdilution method was used to determine minimal inhibitory concentration (MIC) range and values for MIC50 and MIC90. Resistance of a strain to an antimicrobial agent was determined by use of the breakpoint value when available. RESULTS: Isolates were generally susceptible to penicillin, ampicillin, ceftiofur, gentamicin, apramycin, neomycin, spectinomycin, chlortetracycline, erythromycin, tilmicosin, enrofloxacin, and florfenicol, and most isolates were resistant to clindamycin, tylosin tartrate, and tiamulin regardless of the time period. A substantial increase in resistance to sulfa-chlorpiridazine, sulfadimethoxine, sulfathiazole, and trimethoprim-sulfamethoxazole was observed, and a minor increase in resistance to oxytetracycline was also detected. Several multiresistance patterns were observed, most frequently among isolates recovered in the 2003 to 2004 interval. CONCLUSIONS AND CLINICAL RELEVANCE: Ceftiofur, florfenicol, and enrofloxacin are recommended for treatment of infections caused by P multocida subsp multocida in Spain. Increased frequency of resistance to oxytetracycline and sulfonamide drugs may be a contraindication for their use.

Animals↗
PubMed1996

Ultraviolet radiation-induced production of superoxide radicals by selected antibiotics.

The ability of certain drugs and chemicals to induce cutaneous phototoxicity and DNA damage has been attributed to free radical formation during photolysis. In this context we have observed that the synergistic action of commonly used antibiotics and ultraviolet radiation (UVR) exhibited strong superoxide radical (O2-) generation potential in the following order: benzylpenicillin > amphotericin > ampicillin > nystatin > spectinomycin > gentamicin. Commercially available penicillin, nystatin, ampicillin and gentamicin also generated O2- under similar conditions. The results suggest that due precaution are necessary to avoid UVR after the intake of photoreactive drugs.

Anti-Bacterial Agents↗
PubMed2005

A survey on antibiotic usage in dairy herds in Pennsylvania.

A survey was conducted (July 2001 to June 2002) on antibiotic usage of 113 dairy herds from 13 counties in Pennsylvania. Fifty percent of dairy farms surveyed maintained antibiotic treatment records. Only 21% of dairy producers had written plans for treating sick animals. Thirty-two percent of dairy producers sought veterinarian advice before administering antibiotics and on most farms (93%), antibiotics were administered by the owner/manager or designated herdsman. Twenty-four percent of the dairy producers said they always completed the course of antibiotic treatment. Any extra-label use of antibiotics was administered only on the guidelines of a veterinarian on majority of the farms. Comprehensive records from 33 dairy farms indicated that antibiotic usage was largest for calves with enteritis (36%) followed by pneumonia in calves (25%) and foot rot in cattle (16%). Twenty-four antibiotics including beta-lactams, spectinomycin, florfenicol, and tetracyclines were used on these farms. Beta-lactam antibiotics were used mostly for dry cow therapy, clinical mastitis, and on some farms for pneumonia and metritis. On 18% of the dairy herds surveyed, ceftiofur was used in an extra-label manner to treat mastitis in lactating cattle. On 70% of farms, calves were fed medicated milk replacers containing oxytetracycline and neomycin. The results of this study suggest that antibiotics are used extensively on dairy herds for both therapeutic and prophylactic purposes. Beta-lactams and tetracyclines were the most widely used antibiotics. There is considerable variation in the management practices associated with antibiotic use on dairy farms. It is anticipated that the findings of this survey will permit developing new strategies for prudent use of antibiotics on dairy herds.

Animals↗
PubMed1997

Annual report of the Australian Gonococcal Surveillance Programme 1996.

In 1996 the Australian Gonococcal Surveillance Programme (AGSP) examined 2,753 isolates of Neisseria gonorrhoeae. The source of isolates, site of infection and antibiotic susceptibility patterns showed considerable regional variation. Strains examined in Adelaide, Sydney and Melbourne were predominantly from male patients where rectal and pharyngeal isolates were common. Cases in other centres had a much lower male:female ratio and most were genital tract isolates. Resistance to the penicillin and quinolone groups of antibiotics was highest in Sydney and Melbourne. Gonococcal resistance to the penicillins was similar to previous years. Quinolone-resistant Neisseria gonorrhoeae (QRNG) were isolated mostly from overseas travellers. However, some local transmission of QRNG was documented in Sydney. All isolates were sensitive to spectinomycin and ceftriaxone.

Australia↗
PubMed1997

Antimicrobial resistance in gonococci, WHO Western Pacific Region, 1996. The WHO Western Pacific Region Gonococcal Antimicrobial Surveillance Programme.

The World Health Organization (WHO) Western Pacific Region Gonococcal Antimicrobial Surveillance Programme is a multicentric long term programme for continuous surveillance of the antimicrobial susceptibility of Neisseria gonorrhoeae. In 1996 the programme examined the susceptibility of 8,421 isolates of gonococci to various antimicrobials in 17 focal points. A trend toward increased resistance noted in earlier years continued. The proportion of quinolone resistant gonococci reported from most centres either remained stable or increased. More than 50% of isolates in Hong Kong, China, Korea, Cambodia and the Philippines had altered quinolone susceptibility. Resistance to the penicillins was again widespread, and chromosomal mediated resistance was of increasing importance. Penicillinase producing Neisseria gonorrhoea were present in all but one centre. All isolates were sensitive to the third generation cephalosporins and only a very few isolates were spectinomycin resistant. A high proportion of isolates in a number of centres had high level tetracycline resistance, but the proportion of tetracycline resistant Neisseria gonorrhoea in most centres was less than 10%.

Asia, Southeastern↗
PubMed1998

Annual report of the Australian Gonococcal Surveillance Programme, 1997.

The Australian Gonococcal Surveillance Programme (AGSP) examined 2,817 isolates of Neisseria gonorrhoeae in the period 1 January to 31 December 1997, a number similar to that reported in 1996. The biggest change in incidence of gonococcal disease occurred in New South Wales and Queensland where a 20% rise in the number of isolates was noted. In the latter case this was due to improved surveillance, but in the former represented a real increase. The sites of infection and antibiotic susceptibility patterns varied considerably between regions reflecting considerable differences between rural and urban gonorrhoea in Australia. Strains examined in South Australia, New South Wales and Victoria were predominantly from male patients and rectal and pharyngeal isolates were common. In other centres the male to female ratio was lower and most isolates were from the genital tract. Resistance to the penicillin and quinolone groups of antibiotics were also highest in urban centres, but penicillins remained suitable for use in many parts of rural Australia. Quinolone resistance in gonococci continued to increase. This was particularly so in Sydney where quinolone resistant N. gonorrhoeae (QRNG) accounted for about 15% of all isolates and spread of QRNG was predominantly by local contact. QRNG in other centres continued to be isolated at a lower frequency, mostly from overseas travellers. All isolates remained sensitive to spectinomycin and ceftriaxone.

Australia↗
PubMed1999

Annual report of the Australian Gonococcal Surveillance Programme, 1998.

The Australian Gonococcal Surveillance Programme examined 3,583 isolates of Neisseria gonorrhoeae in 1998. Again in 1998 the rates and sites of infection and antibiotic susceptibility patterns varied considerably between regions, reflecting considerable differences between rural and urban gonorrhoea in Australia. Resistance to the penicillin and quinolone groups of antibiotics was highest in urban centres, but penicillins remained suitable for use in many parts of rural Australia. Quinolone-resistant gonococci continued to be concentrated in New South Wales (NSW) where sustained domestic transmission of these strains was maintained but at a lower rate than in 1997. Endemic transmission of Quinolone-resistant gonococci in homosexually active men was found for the first time. Quinolone-resistant gonococci in other centres continued to be isolated mostly from overseas travellers and at a lower frequency. All isolates remained sensitive to spectinomycin and ceftriaxone. Strains showing high level tetracycline resistance increased by 300% in NSW and were acquired predominantly through local contact. A significant increase in the number of isolates was recorded in NSW and Victoria in 1998, this increase being mainly attributable to an increase in gonorrhoea in homosexually active males. Strains examined in South Australia (SA), NSW and Victoria were predominantly from male patients and rectal and pharyngeal isolates were common. In other centres the male to female ratio was lower, and most isolates were from the genital tract in rates similar to those occurring in 1997.

Australia↗
PubMed2000

Surveillance of antibiotic resistance in Neisseria gonorrhoeae in the WHO Western Pacific Region, 1998. The WHO Western Pacific Gonococcal Antimicrobial Surveillance Programme.

Effective treatment of gonorrhoea in the World Health Organization's Western Pacific Region is hampered by the emergence and spread of antibiotic resistant strains of Neisseria gonorrhoeae. A programme of surveillance of gonococcal susceptibility to antibiotics (GASP) continued in the region in 1998. A high proportion of isolates in many participating countries was resistant to quinolones and penicillins, continuing trends observed by this programme since 1992. Resistance to the later generation cephalosporins and to spectinomycin was absent or infrequent. Options for effective treatment of gonorrhoea in the region have been severely compromised by antibiotic resistance.

Asia, Southeastern↗
PubMed2000

Annual report of the Australian Gonococcal Surveillance Programme, 1999.

The primary aim of the Australian Gonococcal Surveillance Programme (AGSP) is to monitor the antibiotic susceptibility of Neisseria gonorrhoeae. In 1999 the AGSP examined 3,740 isolates of gonococci from all States and Territories. The rates and sites of infection and antibiotic susceptibility patterns varied considerably between regions, reflecting the considerable differences between non-urban and urban gonorrhoea in Australia. Resistance to the penicillin and quinolone groups of antibiotics was highest in urban centres. Although penicillins remained suitable for use in many parts of non-urban Australia, enhanced surveillance is required as levels of resistance increase. Endemic transmission of quinolone-resistant gonococci (QRNG) in homosexually active men increased substantially in New South Wales and Victoria where more then 90% of all QRNG were found. QRNG in other centres continued to be isolated mostly from overseas travellers and at a low frequency. All isolates remained sensitive to spectinomycin and ceftriaxone. A further increase in the number of gonococcal isolates from homosexually active men was recorded in New South Wales and Victoria. Strains examined in South Australia, New South Wales and Victoria were predominantly from male patients and rectal and pharyngeal isolates were common. In other centres the male to female ratio of cases was lower, and most isolates were from the genital tract in rates similar to those occurring in previous years. The impact of non-culture based detection methods will adversely affect the ability of the AGSP to monitor trends in gonococcal disease in future years.

Australia↗
PubMed2001

Annual report of the Australian Gonococcal Surveillance Programme, 2000.

The Australian Gonococcal Surveillance Programme (AGSP) monitors the antibiotic susceptibility of Neisseria gonorrhoeae isolated in all States and Territories. In 2000 the in vitro susceptibility of 3,468 isolates of gonococci was determined by standardised methods. Antibiotic susceptibility patterns varied considerably between regions. Resistance to the penicillins was highest in larger urban centres and warrants close attention in those rural centres where treatment with the penicillins continues. Quinolone resistance in gonococci became more widespread in Australia in 2000. Endemic cycles of transmission of quinolone-resistant gonococci (QRNG) in homosexually active men continued in Victoria but declined in New South Wales. Heterosexual endemic transmission of QRNG increased substantially in New South Wales and the proportion of all gonococci represented by QRNG also increased markedly in Queensland and Western and South Australia. All isolates remained sensitive to spectinomycin, but a small number of isolates in a number of jurisdictions showed some decreased susceptibility to ceftriaxone. Strains examined in South Australia, New South Wales and Victoria were predominantly from male patients and rectal and pharyngeal isolates were common. In other centres the male to female ratio of cases was lower, and most isolates were from the genital tract.

Anti-Bacterial Agents↗
PubMed2001

Surveillance of antibiotic resistance in Neisseria gonorrhoeae in the WHO Western Pacific Region, 2000.

A long-term program of surveillance of antimicrobial resistance in Neisseria gonorrhoeae isolated in the World Health Organization's Western Pacific Region (WHO WPR GASP) continued in 2000. About 11,000 gonococci were examined in 15 focal points. Widespread resistance to the penicillin group of antibiotics was confirmed. Resistance to quinolone antibiotics, already widely dispersed, increased further with a shift to higher levels of resistance in many centres. Gonococci with decreased susceptibility to third generation cephalosporins were observed in 5 centres. Spectinomycin resistance was infrequently encountered. Options for cheap and effective treatment of gonorrhoea in the WPR are increasingly limited.

Anti-Bacterial Agents↗
PubMed2002

Annual report of the Australian Gonococcal Surveillance Programme, 2001.

The Australian Gonococcal Surveillance Programme monitors the antibiotic susceptibility of Neisseria gonorrhoeae isolated in all States and Territories. In 2001 the in vitro susceptibility of 3,641 isolates of gonococci from public and private sector sources was determined by standardised methods. Antibiotic susceptibility patterns again varied considerably between regions. Resistance to the penicillins remained high in larger urban centres and warrants close attention in those rural centres where treatment with the penicillins continues. Quinolone resistance in gonococci (QRNG) became more widespread in Australia in 2001 and MICs increased. Nationally, 17.5 per cent of all isolates were QRNG. Endemic cycles of transmission of QRNG in homosexually active men declined further, but heterosexual transmission increased substantially. All isolates remained sensitive to spectinomycin. A small number of isolates in a number of jurisdictions again showed some decreased susceptibility to ceftriaxone. A high proportion of gonococci examined in larger urban centres were from male patients, and rectal and pharyngeal isolates were common. In other centres and in rural Australia the male to female ratio of cases was lower, and most isolates were from the genital tract.

Australia↗
PubMed2003

Annual report of the Australian Gonococcal Surveillance Programme, 2002.

The Australian Gonococcal Surveillance Programme (AGSP) monitors the antibiotic susceptibility of Neisseria gonorrhoeae isolated in all states and territories. In 2002 the in vitro susceptibility of 3,861 isolates of gonococci from public and private sector sources was determined by standardised methods. Antibiotic susceptibility patterns again varied considerably between jurisdictions and regions. Resistance to the penicillins nationally was at 18 per cent but ranged up to 22 per cent in larger urban centres. Quinolone resistance in gonococci (QRNG) remained widespread. Nationally 10 per cent of all isolates were QRNG, and most of this resistance was at high MIC levels. All isolates remained sensitive to spectinomycin. A small number of isolates demonstrated some decreased susceptibility to ceftriaxone (MIC 0.06 mg/L or more) and were concentrated in New South Wales. Patterns of infection were unaltered from previous years. A high proportion of gonococci examined in larger urban centres were from male patients and rectal and pharyngeal isolates were common. In other centres and in rural Australia the male to female ratio of cases was lower, and most isolates were from the genital tract.

Anti-Bacterial Agents↗
PubMed2004

Annual report of the Australian Gonococcal Surveillance Programme, 2003.

The Australian Gonococcal Surveillance Programme monitors the antibiotic susceptibility of Neisseria gonorrhoeae isolated in all Australian states and territories. In 2003 the in vitro susceptibility of 3,772 isolates of gonococci from public and private sector sources was determined by standardised methods. Antibiotic susceptibility patterns again varied considerably between jurisdictions and regions. Resistance to the penicillins nationally, was 17 per cent but ranged up to 27 per cent in larger urban centres. Quinolone resistance in gonococci (QRNG) remained widespread and increased in most states but most markedly in Victoria. Nationally, 14.4 per cent of all isolates were QRNG, and most of this resistance was at high MIC levels. All isolates remained sensitive to spectinomycin. A small number of isolates showed some decreased susceptibility to ceftriaxone (MIC 0.06 mg/L or more) and were concentrated in New South Wales. A high proportion of gonococci examined in larger urban centres were from male patients and rectal and pharyngeal isolates were common. In other centres and in rural Australia the male to female ratio of cases was lower, and most isolates were from the genital tract. In New South Wales, the number of available cultures decreased and represented 30 per cent of the national total. In Victoria, the number of isolates increased and was 25 per cent of all gonococci examined.

Adolescent↗