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PubMed1985

Aztreonam in the treatment of serious orthopedic infections.

Aztreozam was evaluated in the treatment of a variety of orthopedic infections. Included were 17 patients with osteomyelitis, three with purulent arthropathy with prostheses, and 16 with superficial infections secondary to trauma or surgical procedure. Pathogens were gram-negative bacilli sensitive to aztreonam. Concomitant antibiotics were administered for gram-positive cocci that were present initially or by superinfection. Infecting organisms included Pseudomonas aeruginosa (minimal inhibitory concentration 4 to 16 micrograms/ml), Serratia marcescens, Enterobacter cloacae, Enterobacter sakazakii, Morganella morganii, Citrobacter freundii, Proteus vulgaris, Proteus rettgeri, Acinetobacter calcoaceticus and others (all with minimal inhibitory concentrations less than 1.0 microgram/ml). Dosage of aztreonam was 2 to 8 g per day administered intravenously or intramuscularly for five to 52 days. Clinical and bacteriologic responses were adequate in all instances. Recurrences were observed in two individuals with osteomyelitis and one with purulent arthropathy. Adverse clinical or laboratory observations were infrequent and inconsequential.

Adult↗

PubMed1985

New beta-lactam antibiotics in granulocytopenic patients. New options and new questions.

Infectious complications are a frequent cause of morbidity and, at many centers, the major cause of death in patients with cancer. The increased risk and severity of infectious sequelae result from profound alterations in normal host defenses that occur secondary to the underlying malignancy and the treatment thereof. During the last decade, early empiric antibiotic therapy has become standard practice in the initial management of febrile granulocytopenic patients and has contributed significantly to the improved outcome among patients undergoing cancer therapy. Although early death due to unsuspected or inadequately treated bacterial infection has been largely overcome, new problems--also with life-threatening implications--have emerged. As the use of cancer chemotherapy continues to increase, new populations of patients are being placed at increased risk of infection. Defining the host and environmental factors that contribute to this risk assumes central importance for delineating those patients who require the most intense surveillance. Changing medical practices (e.g., increased use of indwelling catheters) have contributed to the emergence of new pathogens. Recent drug developments (e.g., the third-generation cephalosporins and extended-spectrum penicillins) offer new treatment options, as well as generate controversy and confusion. For example, authorities disagree on the optimal duration and modifications in treatment that are required by cancer patients who remain granulocytopenic and who thus are at continued risk of multiple infectious episodes or superinfections. A question of current interest is whether combination therapy with synergistic agents is important in light of the development of the third-generation cephalosporins and extended-spectrum penicillins. Several of these new antibiotics have an exceedingly broad spectrum of activity that includes Pseudomonas aeruginosa, as well as Enterobacteriaceae, Serratia, Citrobacter, indole-positive Proteus, and anaerobes (including Bacteroides fragilis). However, the third-generation cephalosporins are not as active against staphylococci and streptococci as are the first-generation cephalosporins, and none is effective against enterococci. Nonetheless, these agents achieve serum levels that can be 10 to 100 times greater than the minimal inhibitory and bactericidal concentrations of gram-negative bacteria, raising the possibility that these drugs might be effective as single agents. The advantages of the third-generation cephalosporins are their minimal toxicity and long serum half-lives.(ABSTRACT TRUNCATED AT 400 WORDS)

Agranulocytosis↗

PubMed1986

Susceptibility of aerobic gram-negative bacilli to aminoglycosides. Effects of 45 months of amikacin as first-line aminoglycoside therapy.

Amikacin was instituted as the primary empiric aminoglycoside at the San Juan Veterans Administration Medical Center in January 1982; at that time, 16 percent of the strains at the hospital were gentamicin-resistant. A prospective surveillance study was designed to correlate detection of bacterial resistance with aminoglycoside use. In the current report, the baseline period, during which gentamicin was the first-line aminoglycoside, accounting for 61 percent of overall aminoglycoside use, is compared with the period from January 1982 to September 1985, during which the first-line aminoglycoside was amikacin, accounting for 85 percent of overall use. This study is ongoing. During the two periods, the patient population did not differ with regard to aminoglycoside therapy, indications, or overall aminoglycoside use (541 versus 680 patient days per month). Among the gram-negative bacilli isolated, the percent of strains resistant to amikacin was as follows: pre-baseline period/baseline period, 0.8/0.2 percent; amikacin-usage period, 3.6 percent. Resistance to gentamicin and tobramycin during the period of amikacin use decreased from 16 to 11 percent for gentamicin and from 17 to 11 percent for tobramycin. The decrease in resistance of the gram-negative bacilli to gentamicin varied among strains: the resistance of Escherichia coli decreased from 8 to 4 percent; that of Proteus mirabilis, from 12 to 5 percent; that of indole-positive Proteus, from 19 to 12 percent; that of Acinetobacter, from 57 to 23 percent; that of Citrobacter, from 15 to 7 percent; and that of Pseudomonas aeruginosa, from 24 to 16 percent. During the amikacin-usage period, amikacin resistance was unchanged for most strains, with the exception of P. aeruginosa, the resistance of which increased from 4.5 to 7.8 percent. Of the 4,795 strains isolated, 174 were resistant to amikacin; of these, 29 Pseudomonas strains were studied for all mechanisms of resistance. Changes in permeability were exhibited by 11 of the 29 strains; 14 strains exhibited the AAC(6')-I enzyme, 10 strains exhibited the APH(3')-II enzyme, and two strains exhibited ANT(2") in addition to some other unidentified mechanism. Multiple enzyme production was found in 15 of the strains. The use of amikacin as a first-line aminoglycoside is associated with a decrease in resistance to other aminoglycosides and a slight increase in overall resistance to amikacin among aerobic gram-negative bacilli. The usefulness of amikacin has not been affected at our institution.

Acetyltransferases↗

PubMed1986

Aminoglycosides plus beta-lactams against gram-negative organisms. Evaluation of in vitro synergy and chemical interactions.

Combination antibiotic therapy has been used mainly to broaden the antibacterial spectrum and prevent the development of resistance. Antibiotic combinations proven to be synergistic in vitro are associated with a significantly better in vivo response, particularly in the compromised host in whom traditional treatment combines an antipseudomonal penicillin plus an aminoglycoside. Several investigators have examined combining new agents, such as the third-generation cephalosporins (cefotaxime, ceftriaxone, ceftizoxime, ceftazidime, cefoperazone, and moxalactam), aztreonam, or the ureidopenicillins, with amikacin. When compared with combinations of an older cephalosporin, carbenicillin or ticarcillin, plus gentamicin or tobramycin, these newer combinations produce higher rates of clinically meaningful synergy and rapid enhancement of in vitro bactericidal activity against the difficult-to-treat Enterobacteriaceae (i.e., Serratia, Citrobacter, Enterobacter, Providencia, and indole-positive Proteus species). This effect, without any evidence of antagonism, has been reported even for strains moderately or completely resistant to the former antibiotics. Unsatisfactory and unpredictable synergistic interactions against both resistant and susceptible strains of Pseudomonas aeruginosa--the most difficult nosocomial pathogen to treat--have been noted with combinations of tobramycin or gentamicin plus cefotaxime, moxalactam, or cefoperazone. Conversely, the use of amikacin plus various beta-lactams against multi-resistant strains is more frequently synergistic. Agents have been observed to exhibit such synergy in the following order of activity, from most to least synergistic: ceftazidime, ceftriaxone, moxalactam, aztreonam, cefotaxime, azlocillin, cefoperazone, cefsulodin, and carbenicillin. The combination of amikacin plus imipenem or ciprofloxacin against strains of P. aeruginosa resistant to the former and moderately resistant to the latter was recently reported to have a low probability of synergy; the combination of two of the newer beta-lactams had mostly an unpredictable or even antagonistic result. In vitro studies have also demonstrated that high concentrations of the antipseudomonal penicillins can inactivate the aminoglycosides. Among the latter compounds, the inactivation order, from most to least inactivated, was as follows: tobramycin, gentamicin, netilmicin, and amikacin. To date, the reports of aminoglycoside inactivation by the newer cephalosporins have been rather contradictory; only moxalactam has been shown produce a significant decrease in activity.

Amikacin↗

PubMed1986

Antibiotics in the second half of the 1980s. Areas of future development and the effect of new agents on aminoglycoside use.

Articles in this supplement have examined in detail the role of aminoglycosides in the therapy of infections, addressing problems of resistance, toxicity, and efficacy. This article discusses other agents and their potential utility and effect on aminoglycosides. Penem antibiotics, which have activity against only aerobic gram-negative bacteria, have recently been synthesized. These agents have proved effective in animal experiments; to date, however, results of human clinical trials are not available. Carboxypenicillins and ureidopenicillins will still have to be administered with aminoglycosides in patients with serious life-threatening infections or in those institutions in which organisms such as Klebsiella, Enterobacter, and Pseudomonas exhibit high levels of resistance. What will be the role of aminothiazolyl cephalosporins? In some institutions, these agents might be used as sole therapy, particularly if they become less costly as a result of competition. In other settings, concern over the resistance of organisms, such as Enterobacter cloacae, Citrobacter freundii, Serratia marcescens, and Pseudomonas aeruginosa, will result in the use of aminoglycosides with these relatively beta-lactamase-stable cephalosporins. It will be necessary to monitor the development of resistance to the new antibiotics and to determine whether the use of aminoglycosides plus third-generation cephalosporin combinations results in decreased resistance. Other agents to be considered include the directed therapy monobactams aztreonam and carumonam, the broad-spectrum carbapenem imipenem, and the penems under development. It is unclear whether these compounds might be used with aminoglycosides in critically ill, infected patients. It is also unclear what role oral beta-lactamase-stable cephalosporins will have in the therapy of nosocomial infections, since they probably will not be effective against many of the urinary or cutaneous infections that are treated with aminoglycosides. Quinolone agents can be used successfully against many infections. However, the likelihood of bacterial resistance developing and their potential for toxicity are still unknown. Thus, despite the emergence of many new agents, it appears that the time-tested aminoglycosides will continue to play an important role in antimicrobial therapy for some time to come.

Aminoglycosides↗

PubMed1990

Aztreonam susceptibility testing. A retrospective analysis.

Aztreonam is a structurally and immunologically unique beta-lactam antibiotic with activity exclusively against aerobic gram-negative micro-organisms. Between 1983 and 1988, its antimicrobial spectrum was evaluated against more than 5,800 fresh clinical isolates at a 300-bed community teaching hospital. Only 1.1 percent of Enterobacteriaceae isolates were resistant to aztreonam over the five-year study period, an incidence similar to that observed with aminoglycoside antibiotics. Aztreonam was found to be more active than third-generation cephalosporins and comparable with mezlocillin against Enterobacter spp., Morganella, and Citrobacter freundii. Although aztreonam was somewhat less active against nonfermenting gram-negative bacilli, such as Pseudomonas and Acinetobacter, overall more than 90 percent of Pseudomonas aeruginosa isolates were susceptible. Ceftazidime was the most active beta-lactam tested against nonfermenters. Against aerobic gram-positive cocci, aztreonam possessed no clinically useful activity. No significant change in susceptibility to aztreonam was observed over the five-year study period for Enterobacteriaceae. For third-generation cephalosporins, however, a trend toward increased resistance was noted, particularly for Enterobacter spp. and C. freundii. A 50 percent increase in resistance to aztreonam was observed over the five-year study period for nonfermenters, particularly P. aeruginosa and Acinetobacter anitratus. Similar increases in resistance were seen with other beta-lactams and gentamicin. Based on its potent in vitro activity, aztreonam appears to be a useful agent and a desirable alternative to aminoglycoside antibiotics for the treatment of pure aerobic gram-negative bacillary infections, or as a component in combination therapy against mixed infections.

Ampicillin↗

PubMed1990

Serious pediatric infections.

Third-generation cephalosporins are important additions to the range of antibiotics available for treating children with serious bacterial infections. They are highly active against the common pathogens, which cause bacterial meningitis in children. Strains of Haemophilus influenzae type b resistant to both ampicillin and chloramphenicol, and Streptococcus pneumoniae relatively resistant to penicillin remain susceptible to cefotaxime and ceftriaxone. Escherichia coli, Klebsiella pneumoniae, Citrobacter diversus, as well as the other more common gram-negative bacilli isolated from neonates and children are susceptible to these agents. However, Listeria monocytogenes is not cephalosporin-sensitive. Ceftazidime is the only third-generation cephalosporin useful for treating serious infections due to Pseudomonas aeruginosa in children. As with other beta-lactam antibiotics, the clearance of cephalosporins is prolonged in neonates, particularly premature babies. Cefotaxime and ceftriaxone are equivalent to ampicillin and chloramphenicol for the treatment of bacterial meningitis in children over two to three months of age with respect to neurologic outcome and safety, despite the in vitro activity of cefotaxime and ceftriaxone being much greater than the standard antibiotics for the meningeal pathogens. Cefotaxime and ceftriaxone are effective in the treatment of serious gram-negative infections in children. In many instances, ceftriaxone can be administered once daily, which allows for more convenient therapy, particularly on an outpatient basis. Although controversial, ceftazidime has been used as single-agent therapy for empiric treatment of neutropenic immunocompromised children with fever.

Bacterial Infections↗

PubMed1993

A survey of a functional amino acid of class C beta-lactamase corresponding to Glu166 of class A beta-lactamases.

The class C beta-lactamase of Citrobacter freundii GN346 is a typical cephalosporinase comprising 361 amino acids. The aspartic acid at position 217 and glutamic acid at position 219 in this beta-lactamase were, respectively, previously shown not to be the counterpart of Glu166 (ABL166) in class A beta-lactamases, even though sequence alignment of class A and C enzymes strongly suggested this possibility [(1990) FEBS Lett. 264, 211-214; (1990) J. Bacteriol. 172, 4348-4351]. We tried again to assign candidates for the counterpart of Glu166 through sequence alignment based on other criteria, the glutamic acids at positions 195 and 205 in the class C beta-lactamase being selected. To investigate this possibility, these two glutamic acids were changed to glutamine, lysine or alanine, respectively. All the mutant enzymes showed more than 50% of the activity of the wild-type enzyme, indicating that the possibility was ruled out. These results strongly suggested the possibility that the class C beta-lactamase lacks a functional acidic residue corresponding to Glu166 in class A enzymes.

Alanine↗

PubMed1985

Efficacy of bicozamycin in preventing traveler's diarrhea.

Bicozamycin was compared with a placebo in a prospective, randomized, double-blind study of the prevention of acute diarrhea among 30 American travelers newly arrived in Guadalajara, Mexico. None of the 11 subjects given bicozamycin orally for 3 wk at a dosage of 500 mg four times a day developed diarrhea as compared with an incidence of 53% diarrhea (10 of 19 subjects) in the placebo group (p = 0.003). Bicozamycin was well tolerated. Studies of changes in predominant aerobic fecal flora among the 11 subjects treated with bicozamycin showed the appearance of only one highly resistant Citrobacter freundii at the end of 1 wk of therapy and only a total of six resistant isolates at the end of 3 wk. All resistant isolates failed to transfer this resistance to a recipient Escherichia coli. Bicozamycin seems to be well suited and safe as a prophylactic agent against traveler's diarrhea.

Acute Disease↗

PubMed1979

Faecal pollution of surface waters in Jakarta.

Profuse numbers of Enterobacteriaceae were found in samples of surface waters from the Ciliwung River and adjoining canals which criss-cross metropolitan Jakarta and are used widely for domestic purposes by the poorer sections of its population. 15 of the 20 specimens gres E. coli, Klebsiella were isolated from seven and Citrobacter from four. Using enrichment culture procedures, Salmonella sp. were grown from 10 (48%) of 21 water samples examined, and 12 (63%) of aquatic sediments collected at the same sites. Altogether 14 serotypes and 37 Salmonella isolations were recorded. This high degree of faecal contamination of the environment is a major cause of the immense problem of gastro-intestinal infections in that city and probably in many similar cities in developing countries in the tropics.

Enterobacteriaceae↗

PubMed1980

Bacterial colonization of the upper intestine in mild tropical malabsorption.

The bacterial flora of the upper intestine has been examined in symptomatic expatriate adults with mild tropical malabsorption, without steatorrhoea, persisting for many months after return to a western environment. Seven of the 11 patients had enterobacteria in luminal fluid or mucosal samples in numbers ranging from 10(3) to 10(8) per ml or per g. The most common isolate was Klebsiella pneumoniae (in four cases); Citrobacter freundii, Serratia marcescens and Pseudomonas spp. were also detected. The signficance of bacterial colonization in the pathogenesis of mild tropical malabsorption is discussed.

Adult↗

PubMed1986

Magnesium-dependent plaque formation by bacteriophage P1cinC(-) on Escherichia coli C and Shigella sonnei.

Phage P1C(-), in a state of the phage not infective to Escherichia coli K12, was able to form plaques on a wild-type strain of E. coli C and on Shigella sonnei in the presence of Mg2+. Citrobacter freundii, Enterobacter aerogenes, and a Salmonella typhimurium galE mutant were not lysed by, but were lysogenized with P1cinC(-), whereas Klebsiella pneumoniae, Proteus rettgeri, and S. typhimurium LT2 were not susceptible to either P1cinC(-) or P1cinC(+). The lipopolysaccharide structure of E. coli C and Sh. sonnei is discussed with reference to receptors for P1cinC(-) and P1cinC(+).

Bacteriophages↗

PubMed1987

Cell turnover and colon tumor development.

The proliferative characteristics of the large bowel are determined genetically and can vary over a wide range, the lower range being resistant to chemically induced tumors and the upper range expressing susceptibility. Basically, the colon has a relatively high level of cell renewal. It can be further elevated or depressed by a number of dietary and environmental conditions. A hyperproliferative state has been induced by the presence of carrageenan, Citrobacter freundii, nonspecific injury, or dietary factors such as high levels of bile acids. The effect of high proliferation levels is to produce more S-phase cells, which are sensitive to DNA damage, to increase the risk of neoplastic transformation and to shorten the tumor latency period. In animal models, hyperactivity has meant enhanced tumor incidence. A hypoproliferative state has been induced in the colon of man and mouse. Experimentally, the net effect of lower proliferative levels has been to reduce colon tumor incidence. It remains to be determined whether clinical trials involving hypoproliferation can be maintained chronically and are an effective means of reducing colon tumor incidence in high-risk groups.

Animals↗

PubMed1988

The distribution and divergence of DNA sequences related to the Tn21 and Tn501 mer operons.

The mercury resistance (mer) operons of the Gram-negative bacterial transposons, Tn21 and Tn501, are phenotypically indistinguishable and have extensive DNA identity. However, Tn21 mer has an additional coding region (merC) in the middle of the operon which is lacking in Tn501 and there is also a discrete region of the mercuric ion reductase gene (merA) which differs markedly between the two operons. DNA fragment probes were used to determine the distribution of specific mer coding regions in two distinct collections of mercury-resistant (Hgr) Gram-negative bacteria. Colony blot hybridization analysis showed that merC-positive operons occur almost exclusively in Escherichia, although merC-negative operons can also be found in this genus. The merC-negative operons were found in Citrobacter, Klebsiella, and Enterobacter and in some Pseudomonas. Most of the Pseudomonas did not hybridize detectably with either of the two operons studied, indicating that they harbor an unrelated or more distantly related class of mercury resistance locus. Southern hybridization patterns demonstrated that the merC-positive mer operon is well conserved at the DNA level, whereas the merC-negative operons are much less conserved. The presence of merC also correlated with conservation of a specific variant region of the merA gene and with an antibiotic resistance pattern similar to that of Tn21. Tn501 appears to be an atypical example of the merC-negative subgroup of Hgr loci.

Blotting, Southern↗

PubMed1990

Dysgonic fermenter 3-associated abscess in a diabetic patient.

We report a case in which a strain of the U.S.A. Centers for Disease Control (CDC) dysgonic fermenter (DF) 3, together with Citrobacter freundii, was isolated from an abscess in a diabetic patient. DF 3 may be easily overlooked due to its fastidious nature, a characteristic shared with two former DF groups now placed in the genus Capnocytophaga. To our knowledge, this is the first European case report of DF 3-associated infection.

Abscess↗

PubMed1989

The microbial ecology of soybean soaking for tempe production.

Soybeans soaked in tap water for 24 to 36 h at 20, 30 or 37 degrees C underwent a natural fermentation that was characterized by the growth of microorganisms to 10(8)-10(10) cfu/ml (depending on temperature) and a reduction of pH from 6.5 to 4.5. Lactobacillus casei, Streptococcus faecium, Staphylococcus epidermidis and Streptococcus dysgalactiae dominated the fermentation but, significant contributions were also made by Klebsiella pneumoniae, Klebsiella ozaenae, Enterobacter cloacae, Enterobacter agglomerans, Citrobacter diversus and Bacillus brevis, and the yeasts Pichia burtonii, Candida didensiae and Rhodotorula rubra. Fermentation of surface-decontaminated beans in sterile water with pure cultures of these isolates showed L. casei, Strep. faecium and Staph. epidermidis to be the main species responsible for the pH reduction. Soybeans were the main source of microorganisms for the fermentation. Boiled beans did not undergo an acid fermentation.

Bacteria↗

PubMed1991

A new plate medium for rapid presumptive identification and differentiation of Enterobacteriaceae.

A new selective differential agar medium for rapid presumptive identification of Enterobacteriaceae from water and food samples is described (EMX ID agar). By a combination of fluorogenic and chromogenic substrates, the medium detects the presence of beta-D-glucuronidase, beta-D-galactosidase, beta-D-xylosidase, tryptophane deaminase and H2S; additionally, cytochrome-oxidase and indole production can be demonstrated. This medium provides an inexpensive means for simple and rapid presumptive identification of E. coli and coliforms and for the differentiation within the Klebsiella-Enterobacter and the Proteus-Providencia-Morganella group. Furthermore, it allows to distinguish between the H2S-positive Enterobacteriaceae Citrobacter freundii, Salmonella spp., S. arizonae, Edwardsiella, Proteus mirabilis, P. vulgaris and some oxidase-positive bacteria.

Agar↗

PubMed1993

Detection of Salmonella in animal protein by Rappaport-Vassiliadis broth using indirect impediometry.

Indirect impedance methodology for the detection of Salmonella was investigated using a rapid automated bacterial impedance technique (RABIT) system. Four commercially available Rappaport-Vassiliadis (RV) enrichment broths were evaluated for their sensitivity and selectivity in detecting Salmonella using this technique. The RV from Lab M and Oxoid (new) gave the shortest detection times and showed good correlation between Salmonella numbers and detection times. Using Lab M medium, the indirect impedance technique could distinguish between Salmonella spp. and the closely related genera, Proteus and Citrobacter. The impedance technique showed recoveries of Salmonella from processed animal protein and raw meats equivalent to, or better than, those obtained with RV used in a conventional Salmonella isolation procedure.

Animal Feed↗