Pseudomonas aeruginosa endophthalmitis after lung transplantation for cystic fibrosis.
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Biomedical subjects
Publications and source records attributed to A S Prince.
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The kil and kor genes of RK2 are novel genetic determinants further that the kil and kor network constitutes a replication regulon, and that perhaps the function of this regulon is to ensure expression of trfA at appropriate levels. The complexity of this regulon may reflect an ability of the system to adapt to the intracellular environments of a variety of hosts. Indeed, there is tantalizing evidence that regions encoding kil or kor genes are important to host range (1,2,6,28; Schmidhauser and Helinski, pers. comm.). We are therefore hopeful that the study of these genes and the eventual determination of the molecular basis of their actions will lead to a complete understanding of the replication control and broad host range capability of IncP plasmids.
In broad host-range plasmid RK2, korA function prevents the lethal effect of kilA on Escherichia coli host cells and inhibits expression of trfA, the essential replication gene. From gene fusion and promoter replacement studies, we determined that control of kilA is also mediated at the level of gene expression and that the target resides in the kilA promoter region. The nucleotide sequence of this region shows the same two operator-like palindromes present in the previously sequenced promoters of trfA and korA. One of the palindromes (5'-GTTTAGCTAAAC-3') at the -10 position is sufficient to confer sensitivity to korA function. The presence of the same sequences in the korA promoter region suggested that korA might also regulate its own expression. Using the structural gene for chloramphenicol acetyltransferase (cat) fused to the korA promoter, we found that korA gene expression is indeed autoregulated. The results show that korA gene product is very likely a repressor that negatively regulates expression of at least three different genes by interacting with an operator-like sequence in their promoter regions. Coordinate regulation of host-lethal gene kilA and essential replication gene trfA by a common mechanism also supports our hypothesis that these genes are functionally related.
Replication functions with IncP2 specificity were identified on a 3-kilobase DNA fragment isolated from the 400-kilobase Pseudomonas megaplasmid pMG2.
The new penicillins have not been a breakthrough for the pediatrician. Indeed, 20 years ago with the introduction of ampicillin and methicillin and 15 years ago with the introduction of carbenicillin, the pediatrician was given the penicillins that he has used so well to treat trivial and life-threatening infections. The drugs discussed in this article are small steps forward, and whether mezlocillin, azlocillin, or piperacillin will prove more helpful to the pediatrician than have carbenicillin or ticarcillin will be learned in the next few years.
Azlocillin, a semisynthetic ureidopenicillin that inhibits many Gram-negative and Gram-positive bacteria and many Pseudomonas aeruginosa resistant to carbenicillin, was used to treat 23 episodes of infection in 20 patients. The majority of the patients had severe underlying diseases, including marked reduction in renal function in a number of the patients. Infection sites were lung, urinary tract, skin and primary bacteraemia. Seven patients had bacteraemia. Clinical cure or improvement was achieved in 87% of infections, all patients with bacteraemia due to Pseudomonas spp., Escherichia coli, Listeria spp. and Streptococcus faecalis were cured. Cure was achieved with azlocillin against carbenicillin-resistant Ps. aeruginosa infections. Serum and urine levels were easily maintained in excess of the accepted minimal inhibitory concentrations of the susceptible organism (less than or equal to 64 mg/l). Adverse effects were minor. Azlocillin was a safe, well-tolerated and effective agent to treat suspected or proven infections due to Ps. aeruginosa and other susceptible bacteria.
Cloning of specific regions of RK2, a broad host range incompatibility group P plasmid, has revealed three genes: kilA, kilB, and kilC. Each of these genes can cause loss of viability of an Escherichia coli host. This effect on the host is normally prevented by the functions of three additional RK2 genes: korA, korB, and korC. Each kor gene is specific for a particular kil gene. The kil and kor genes are located in four distinct regions of the RK2 genome. The three kil genes are not clustered and, with the possible exception of kilA, they are also well separated from their corresponding kor genes. We have found that the korA and korB determinants are not peculiar to RK2 but instead are highly conserved throughout the incompatibility group P plasmids.
Cloning the gene for gentamicin resistance from Pseudomonas aeruginosa plasmid pMG35 on the high-copy-number Escherichia coli cloning vehicle pMK20 allowed detection of 6'-N-acetyltransferase activity that was not readily detected when the parent plasmid was present either in P. aeruginosa or E. coli.
The in vitro activities of gentamicin, tobramycin, amikacin, azlocillin, carbenicillin, mezlocillin, piperacillin, ticarcillin, cefotaxime, ceftizoxime, cefoperazone, cefsulodin, moxalactam, ceftazidime, ceftriaxone, and N-formimidoyl thienamycin were measured against 62 isolates of Pseudomonas aeruginosa obtained from patients with cystic fibrosis. Ceftazidime and N-formimidoyl thienamycin were the most active of these agents.
Piperacillin sodium, a semisynthetic penicillin that inhibits many Klebsiella and Pseudomonas aeruginosa organisms resistant to carbenicillin, was used to treat 41 episodes of infection in 35 patients. Infectious sites included lungs, urinary tract, and tissue, including peritonitis. Seven patients had bacteremia. Clinical and bacteriological cures were achieved in 85% of infections. Cure was achieved with piperacillin in patients infected with carbenicillin-resistant P aeruginosa and Klebsiella organisms. Adverse effects were minor and included rash in two patients. Serum levels were easily maintained above the inhibitory levels for susceptible organisms. Piperacillin was a safe, well-tolerated, and effective antimicrobial agent.
Aspergillus fumigatus endocarditis developed in a 2 1/2-year-old girl after repair of tetralogy of Fallot. There have been 14 other cases of Aspergillus endocarditis in children described in the literature. Fever and embolic phenomenon, particularly to the CNS, were the most common presenting manifestations. Consumptive coagulopathy developed in this patient as it has in other children and should suggest the diagnosis of Aspergillus endocarditis inasmuch as blood cultures are uniformly negative. Antemortem diagnosis was made in four of 15 patients. Only one patient survived the infection. Environmental surveillance is crucial when a case is encountered. Survival of the infected patient occurs only with early diagnosis and surgical removal of the infected tissue.
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The fluid management of 50 children with Haemohpilus influenzae type B meningitis was reviewed. Clinical hydration status on admission, serum sodium values, and overall fluid balance was assessed to determine the contribution of empiric fluid restriction in preventing the development of syndrome of inappropriate antidiuretic hormone (SIADH). Thirty-three of 50 patients were well hydrated on admission. Sixteen of 50 patients (32%) initially had signs of dehydration and five out of 16 were in shock. Only two patients had evidence of SIADH. Twenty patients were empirically fluid restricted, including one who proceeded to develop SIADH; thirteen were not fluid restricted, and sixteen who were dehydrated received replacement fluids in addition to the usual maintenance fluids. None of these patients developed SIADH. As fluid depletion was more common than excessive fluid retention in our patients, empiric fluid restrictions could not be justified. Careful, individualized monitoring of the clinical state of hydration, electrolytes and osmolaities is suggested to guide the fluid management in these patients.
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Antibiotic-associated colitis is a rare complication of antimicrobial therapy in children. Ampicillin, penicillin, and clindamycin are the drugs most frequently reported to cause pseudomembranous colitis in pediatric patients. This diagnosis should be suspected in any child with significant diarrhea during or after a course of antimicrobial therapy, especially if the diarrhea persists after the drug has been discontinued. The diagnosis is established by proctoscopic findings of typical plaques of pseudomembranes. Most cases resolve promptly when the implicated antibiotic is stopped; however, the disease can be fulminant, progressing to toxic megacolon, peritonitis, and shock. Therapy of patients who have persistent diarrhea after the offending antibiotic has been discontinued should include oral vancomycin. Close fluid management is crucial for survival.
Moxalactam was evaluated as the sole therapy of 45 episodes of infection in 41 patients due primarily to bacteria resistant to older antibiotics. Infections included bacteremias, pulmonary, skin and soft tissue infections, osteomyelitis, and meningitis. Clinical and bacteriological cure was achieved in 69% of infections. Cure was achieved with moxalactam in patients infected with cefazolin-resistant, carbenicillin-resistant, chloramphenicol and gentamicin-resistant organisms. Although adverse reactions were generally mild, diarrhea developed in five patients, a major increase in prothrombin time and bleeding in three patients and a disulfiram reaction in two patients.
Twelve patients who underwent 26 episodes of lower respiratory tract infection due to Pseudomonas aeruginosa were treated with aztreonam. Infectious episodes were severe in 11 patients, moderate in 10 patients, and mild in five patients. In 85% of the episodes, significant clinical improvement occurred, but in four severe episodes, the clinical response was unsatisfactory. The mean interval between initiation of treatment and improvement was seven days. Aztreonam was as clinically effective in the treatment of infections due to organisms susceptible to penicillins active against Pseudomonas as it was in the treatment of infections due to organisms resistant to these agents. P. aeruginosa was not permanently eradicated from the sputum of any of the patients treated with aztreonam. It did not cause any major adverse effects, and the only laboratory abnormality found was an increase in alkaline phosphatase, which occurred during 12 (46%) courses of therapy. Levels of alkaline phosphatase returned to normal after conclusion of treatment. Aztreonam was shown to be clinically effective in the treatment of lower respiratory infections due to P. aeruginosa in patients with cystic fibrosis.