Antimicrobial Drug Therapy Research Articles

Empyema Thoracis fromSalmonellaCholeraesuis

Empyema Thoracis from<i>Salmonella</i>Choleraesuis

Neisseria meningitidisEndotoxin and Capsule Transmission by Transplantation

<i>Neisseria meningitidis</i>Endotoxin and Capsule Transmission by Transplantation

Staphylococcus lugdunensisPacemaker-related Infection

We report the first known case of a device-related bloodstream infection involving Staphylococcus lugdunensis small-colony variants. Recurrent pacemaker-related bloodstream infection within a period of 10 months illustrates the poor clinical and microbiologic response even to prolonged antimicrobial drug therapy in a patient infected with this staphylococcal subpopulation.

Quorum-sensing control in Staphylococci – a target for antimicrobial drug therapy?

Today, we find ourselves in an urgent need for novel antibacterial drugs, as many important human pathogens have acquired multiple antibiotic resistance factors. Among those, Staphylococcus aureus and S. epidermidis play a major role as the leading sources of nosocomial infections. Recently, it has been suggested to develop therapeutics that attack bacterial virulence rather than kill bacteria. Such drugs are called “antipathogenic” and are believed to reduce the development of antibiotic resistance. Specifically, cell-density-dependent gene regulation (quorum-sensing) in bacteria has been proposed as a potential target. While promising reports exist about quorum-sensing blockers in gram-negative bacteria, the use of the staphylococcal quorum-sensing system as a drug target is now seen in an increasingly critical way. Inhibition of quorum-sensing in Staphylococcus has been shown to enhance biofilm formation. Furthermore, down-regulation or mutation of the Staphylococcus quorum-sensing system increases bacterial persistence in device-related infection, suggesting that interference with quorum-sensing would enhance rather than suppress this important type of staphylococcal disease. The chemical nature and biological function of another proposed staphylococcal quorum-sensing inhibitor, named “RIP”, are insufficiently characterized. Targeting quorum-sensing systems might in principle constitute a reasonable way to find novel antibacterial drugs. However, as outlined here, this approach requires careful investigation in every specific pathogen and type of infection.

Antibiotics, new pathogens, new drug resistance

The 20th century is the century of the discovery of numerous pathogenic microorganisms. It is also the century of discovery of antimicrobial drugs and the beginning of the antibiotic era. While the development of antifungal drugs and of antivirals is on its rise, many infectious disease physicians and microbiologists feel that we might be on the edge of the beginning of the post-antibiotic era--50 years after antibiotic use in man and animals. Antibiotics have certainly been a major progress in modern medicine. Mortality and morbidity from many infectious diseases have been substantially reduced by effective antimicrobial therapy. The use of antibiotics has also been a prerequisite for major advances in clinical oncology, transplantation medicine, and surgery. The emergence and spread of resistant pathogens, however, has necessitated the development of broader and more active drugs and has resulted in excessive antimicrobial drug use with consequent selective pressure. Every 3rd patient admitted to a hospital is given antibiotics--often in the form of stepwise escalated therapy eventually including combinations of expensive agents. If the aim is to minimize the emergence of resistance and to contain costs, a much more critical indication for antimicrobial drug therapy will be necessary. Also, programmes on a local, regional, and perhaps even national level will be needed to help rationalize antimicrobial drug use.

Preventing catheter-related bacteriuria: should we? Can we? How?

Up to 25% of hospitalized patients undergo urinary catheterization, and about 5% develop bacteriuria each day of catheterization. Catheter-related bacteriuria is associated with increased morbidity and mortality. We performed an evidence-based synthesis of the literature on preventing catheter-associated urinary tract infections (UTIs) to develop recommendations for clinicians. Catheterization should be avoided when not required and when needed, should be terminated as soon as possible. Use of suprapubic and condom catheters may be associated with a lower risk of UTI than use of urethral catheters. Aseptic catheter insertion and a properly maintained closed drainage system are crucial to reducing the risk of bacteriuria. Instillation of antimicrobial agents into the bladder or urinary drainage bag and rigorous meatal cleansing seem to be of little benefit. Use of urinary catheters coated with silver alloy may reduce the risk of UTI. Systemic antimicrobial drug therapy seems to prevent UTIs, but primarily for patients catheterized for 3 to 14 days. Antibiotic drug prophylaxis is especially valuable in patients undergoing transurethral resection of the prostate or renal transplantation. Using these methods, urinary catheter-associated UTI can often be prevented for weeks, but not longer terms.

Microbiologic characteristics of persistent otitis media.

To identify the pathogens isolated from children with acute otitis media who did not respond to antimicrobial drug therapy. Retrospective analysis of cultures obtained by tympanocentesis from 46 children. Organisms were recovered from 34 children (74%), and 43 isolates were recovered from these individuals. The organisms were Streptococcus pneumoniae (16 isolates), Haemophilus influenzae non-type b (12 isolates), Moraxella catarrhalis (5 isolates), Streptococcus pyogenes (5 isolates), Staphylococcus aureus (3 isolates), and Peptostreptococcus species (2 isolates). Resistance to the antimicrobial agent used was found in 27 (63%) of 43 isolates found in 22 patients (48%). Of patients who did not respond to amoxicillin therapy, H influenzae predominated. Streptococcus pneumoniae was recovered from 5 (56%) of 9 of those who did not respond to trimethoprim and sulfamethoxazole therapy, 4 (44%) of 9 patients after azithromycin therapy, 3 (25%) of 12 patients after amoxicillin therapy, and 2 (40%) of 5 patients after cefixime therapy. Streptococcus pyogenes was recovered from 2 (40%) of 5 patients after trimethoprim and sulfamethoxazole therapy and from 2 (40%) of 5 patients after cefixime therapy. The data illustrate the relation between resistance to antimicrobial drug therapy and failure of patients with otitis media to improve. They also highlight the importance of diagnostic tympanocentesis in establishing the presence of resistant microorganisms.

Bacterial Urinary Tract Infections

Bacterial urinary tract infection rarely is the initial cause of lower urinary tract disease in cats; however, a substantial number of cats with various lower urinary tract disorders develop urinary infections as a complication of the underlying disease or its treatment. Examination of urine sediment for pyuria is a good screening test for urinary tract infection, but results of urine cultures are needed to diagnose such infections reliably, as well as to guide therapeutic decisions. Appropriate antimicrobial drug therapy is the cornerstone of treatment for urinary tract infection. Treatment of the underlying urinary disorder also is important, and follow-up urine cultures should be performed to determine therapeutic outcome.

Personal Computer-based Expert System for Quality Assurance of Antimicrobial Therapy

A personal computer (PC)-based expert system developed to monitor the appropriateness of antimicrobial therapy is described. Susceptibility test data and antimicrobial therapy data are downloaded daily from the microbiology department and pharmacy department computer systems. Relational database software allows for the indexing, sorting, and manipulation necessary for analysis. The expert system accomplishes its analyses using (1) databases of organisms, antimicrobial drugs, and susceptibility cutoff values, (2) programs for evaluating pathogenicity and therapy, and (3) algorithms that determine the timing and sequence of the analysis. System output consists of discrepant therapy reports that indicate that no therapy is being given despite the presence of pathogens, that the pathogens isolated are resistant to the therapy being given, that the therapy cannot be matched with susceptibility data on the isolates, or that the therapy was discontinued too quickly. The expert system has been in continuous operation at an 800-bed referral hospital since July 1991. During an 11-month period, the system generated 1538 discrepant therapy reports. The percentage of isolates resulting in reports varied substantially with the source of the isolate. Therapy was more likely to be improved when the physician was contacted about the potential problem indicated by the report than when the physician was not contacted. A PC-based expert system using data from unlinked pharmacy and microbiology computer systems automatically evaluated the appropriateness of antimicrobial drug therapy in light of susceptibility test data.

Red cell transfusion therapy for anemia in patients with AIDS and ARC: incidence, associated factors, and outcome

The records of the San Francisco General Hospital (SFGH) Blood Bank were reviewed, and 263 likely AIDS and AIDS-related complex (ARC) patients were identified, who received 1545 units of packed red cells (PBRCs) between July 1, 1987, and June 30, 1988. A probability sample of 80 of these patients was selected randomly for detailed chart review. Of this sample, 78 (98%) were confirmed to have AIDS (86%) or ARC (14%). On the basis of the yearly census of the SFGH AIDS clinic, a transfusion incidence of 0.89 PRBC units per patient per year for patients with AIDS and 0.27 PRBC units per patient per year for those with ARC was estimated. Whereas 26 percent of the 177 transfusions studied in detail involved more than one associated (possibly causative) factor, antimicrobial drug therapy, zidovudine therapy, and disseminated Mycobacterium avium complex (MAC) infection were the sole associated factors in 20, 14, and 12 percent of the transfusions, respectively. To assess the role of MAC, the 263 transfused patients were compared with the 574 patients whose blood was submitted to the SFGH Mycobacteriology Laboratory during the same period. Patients whose blood yielded MAC had a relative risk of 5.2 for transfusion-requiring anemia. In 80 percent of cases, the patient returned home after transfusion. Most PRBC transfusions administered to AIDS or ARC patients were optimal therapy.

The surgery for pulmonary tuberculosis.

The surgery for pulmonary tuberculosis.

Relationship of inappropriate drug prescribing to increased length of hospital stay

The relationship of inappropriate drug prescribing to increased length of hospital stay was studied. The medical records of 77 cases of pyelonephritis were reviewed retrospectively. Appropriateness of antimicrobial drug therapy was judged by three types of explicit screening criteria: drug-specific, patient-specific, and match of drug to infecting organism. Patients whose therapy passed all the criteria were hospitalized, on the average, two days less than those whose therapy failed one or more of the criteria. This was a significant difference (p less than 0.05). Age, seriousness of the pyelonephritis, or method of payment appeared to have no significant moderating effect on this result. However, the increased length of stay may not have been associated with only inappropriate prescribing, because the inappropriately prescribing physicians kept their patients hospitalized longer beyond the point of symptom remission than did the appropriately prescribing physicians. The study suggest that successful interventions for improving drug therapy could result in large cost savings.

Antimicrobial Drug Therapy in Pediatric Practice

Knowledge of the interactions of drugs and bacteria, the undesired side effects of antibacterial agents, and the host factors important for optimal results have contributed to better understanding of the effects of antimicrobial agents on host and parasite and is the basis for intelligent use of these drugs. The current status of antibacterial therapy of acute pyogenic bacterial diseases is summarized.

Pelvic tuberculosis

The 132 cases reviewed give further evidence of the effectiveness of antimicrobial drug therapy in the treatment of pelvic tuberculosis. The patient, in most instances, should receive the initial treatment in a sanatorium, and although the stay need not be prolonged, the drug therapy must be continued for 18 to 21 months. Surgery has now largely a diagnostic role to play in the management of pelvic tuberculosis.The failure of any of the patients in this series to achieve an intrauterine pregnancy after treatment is not evidence of therapeutic failure because, in most instances, the Fallopian tubes have been irreparably damaged before antimicrobial drug therapy has been started.

Surgical treatment of mycotic aneurysms.

Mycotic aneurysms are uncommon arterial lesions that arise as a complication of septicemia, usually that of subacute bacterial endocarditis. 1,10,12 Before the advent of antimicrobial drug therapy, blood stream infections rarely healed and metastatic abscesses of the arterial wall appeared almost invariably as terminal phenomena; even if the lesions were recognized before death, the clinical course often made repair impossible or rendered the result fruitless. The loss of life and limb following surgical intervention—consisting of ligation, excision, or aneurysmorrhaphy—was high. 8,13 The introduction of antibiotics profoundly changed the clinical outlook of septicemias, and with the therapeutic means at hand to sterilize the blood stream mycotic aneurysms assumed a more favorable position from the viewpoint of surgical treatment. The development of techniques of vascular replacement afforded opportunity for the surgeon to remove the aneurysm and restore arterial continuity. With the newer vascular procedures available, attempts at the cure of mycotic

The rôle of surgery in the treatment of pulmonary tuberculosis: Anderson W. Med. Press and Circular, 1935, 96, 125

The records of 9939 patients hospitalized for tuberculosis between 1963 and 1972 inclusive were reviewed with respect to patients who were treated surgically. During this period there was a steady decline in the number of patients thus treated; the success of antimicrobial drug therapy has altered the frequency of various surgical procedures, and pulmonary resection is now the procedure of choice, with a growing reluctance to perform segmental resection. Morbidity and complications among the patients in this series have been within acceptable limits. The problem of residual space has been minimal. Bronchopleural fistula with empyema (incidence, 3.1%) has been the most serious complication, accounting for the largest proportion of deaths. The mortality of 2.8% is comparable to that reported in the literature. Though mild to moderate respiratory insufficiency developed in some patients, none was seriously incapacitated. The majority of surviving patients have remained well, with their disease under control. In a number of patients reactivation of the disease occurred, probably because of conservative resection and discontinuance of drug therapy due to misunderstanding between patient and physician.