Treatment Of Established Infection Research Articles

Immunotherapy and immunoprophylaxis in bone marrow transplantation

Immunotherapy can be defined as treatment directed at augmenting host immune defence mechanisms. Non-antimicrobial therapies and immunoprophylaxis in bone marrow transplantation (BMT) can be subdivided into three broad categories: passive immunotherapy with intravenous immunoglobulin (IVIG); cytokine therapy; and anti-endotoxin-directed treatments. Most studies using IVIG in BMT are prophylactic and suffer from variability in study design, type of IVIG and dosing regimens. Various effects on viral and bacterial infections and graft-versus-host disease (GVHD) have been reported but few if any have shown benefit in terms of improved patient survival. Moreover the immunomodulatory effect of immunoglobulin G preparations is frequently overlooked. With the exception of cytomegalovirus (CMV) pneumonitis, there is little evidence of benefit in the treatment of established infections and the relative benefits of hyperimmune preparations are poorly established. The development of haemopoietic growth factors has led to the widespread use of cytokines in BMT. The benefits of these agents both in the prevention of fever and infection and as adjuvants to standard antimicrobial therapy in established infection (e.g. invasive mycoses) are rapidly becoming apparent. Both human recombinant granulocyte-macrophage colony-stimulating factor (rhGM-CSF) and granulocyte colony-stimulating factor (rhG-CSF) have been shown to accelerate granulocyte recovery following BMT and reduce fever days, antibiotic usage and hospitalization. RhGM-CSF appears superior in these respects. The roles of interleukin 1 (IL1), IL3, IL6 and interferons are also under evaluation. As with the much publicised studies using anti-endotoxin antibodies as therapy in sepsis, there is little evidence of benefit in the few studies performed in BMT patients. Other strategies using prophylactic IVIG enriched for anti-endotoxin antibodies appear more promising. The concept of neutralizing the production of cytokines with monoclonal antibodies, receptor antagonists or other biological modifiers, is mainly directed at reducing tissue damage during the preparative regimen with the aim of reducing subsequent GVHD. Any effect this may have on infectious complications such as CMV disease has yet to be investigated. Cloned T cells cytotoxic against CMV have also been developed and studies using these preparations are underway.

Host defense mechanism in the pathogenesis of UTI and UTI in immunocompromised patients

Defects in the immune system determine the clinical manifestations and severity of urinary tract infections (UTI) and the rates of complication but they only have an indirect role in influencing susceptibility to infection. The rates of UTI in diabetics, renal transplant, recipients, neutropenic patients, and patients with AIDS are primarily determined by the degree and duration of urinary tract manipulation and the higher perineal prevalence of potential pathogens that result from frequent hospitalization and antimicrobial use. Prompt recognition and treatment of established infections is critical to prevent life-threatening complications (e.g. bacteremia, emphysematous pyelonephritis) but routin screening for asymptomatic bacteriuria is indicated only in kidney recipients less that 3 monhts post-transplantation.

Development of a 14C-urea breath test in ferrets colonised with Helicobacter mustelae: effects of treatment with bismuth, antibiotics, and urease inhibitors.

A 14C-urea breath test analogous to its clinical counterpart is described for use in ferrets naturally or experimentally infected with Helicobacter mustelae. The test is performed within a sealed glass metabolism chamber through which air is drawn at a constant rate and expired breath collected into sodium hydroxide. Peak 14CO2 production occurred approximately 1 hour after substrate administration. Both inter- and intra-animal responses were highly reproducible, with mean coefficients of variation less than 10%. Other than enhancing peak 14CO2 levels very slightly, fasting had little influence on the response. In infant animals challenged with H mustelae, breath test activity increased linearly with the total count of culturable bacteria isolated from the antrum. Treatment of established infections with colloidal bismuth subcitrate (DeNol) for 4 weeks resulted in clearance of all detectable bacteria but retention of some breath test activity. Subsequent regrowth of bacteria was parallelled by an increase in the breath test response. Inclusion of amoxycillin and metronidazole in the treatment regimen, however, eradicated all the bacteria and almost totally eliminated 14CO2 production. This response parallels the clinically observed suppressive effect on H pylori achieved with bismuth alone relative to the total eradication seen with triple therapy. A single oral dose of the urease inhibitor, flurofamide, inhibited over 90% of the response for at least 24 hours. Acetohydroxamic acid was less effective. These findings suggest that in the ferret H mustelae model, breath test analysis can be a useful, non-invasive alternative to endoscopy for evaluation of agents affecting either growth of the organism or urease activity.

Differential response to benzylpenicillin in vivo of tolerant and non-tolerant variants of Streptococcus sanguis II

A variant that was highly tolerant to benzylpenicillin was obtained from a non-tolerant clinical isolate of Streptococcus sanguis II by repeated exposure to penicillin. The rabbit model of endocarditis was used to investigate the efficacy of a high dose regimen of benzylpenicillin (250 mg/kg; peak serum concentration c. 25 mg/l) in the prophylaxis and treatment of endocarditis during challenge or infection with the non-tolerant parent strain or its tolerant variant. The two strains exhibited a similar capacity to initiate infection. A single dose of penicillin administered 0.5 h before bacterial challenge protected six of nine rabbits infected with the non-tolerant parent strain, but none of nine infected with the tolerant variant. Treatment of established infection with penicillin administered twice daily for four days cured eight of 13 (61%) rabbits infected with the non-tolerant parent strain, but only one of 14 (7%) rabbits infected with the tolerant variant. These results support the view that tolerance to penicillin has therapeutic implications.

Oral chemotherapy of fatal B virus (herpesvirus simiae) infection

Acyclovir and ganciclovir, which were only about 10-fold less effective against B virus than herpes simplex virus type 1 in VERO cells, were tested in vivo in B virus-infected rabbits. Untreated control rabbits became paralysed from 8 days and died from 10 days. Oral acyclovir at a dose rate of 500 mg/kg/day for 21 days prevented death; acyclovir prevented disease at 700 mg/kg/day. In B virus-infected humans such a high dose of acyclovir could not be given by mouth. Nevertheless, high dose oral acyclovir is suggested for immediate prophylaxis when monkey handlers have been exposed to potentially fatal B virus infection. Should signs or symptoms of disease occur then high dose intravenous acyclovir has been recommended. Since ganciclovir was found to be more effective than acyclovir, intravenous ganciclovir might be preferred for the treatment of established infection.

Colorectal Trauma

Colorectal injury remains a source of significant morbidity and mortality. Gunshot and stab wounds are the most common etiologic agents. Diagnosis is usually established on clinical grounds. For the purposes of management, the large bowel can be considered as colon and rectum. Minor colon injuries can be repaired primarily; management of major colon injuries or injuries associated with multiple organ involvement, significant blood loss, or massive contamination should be individualized. Diversion or exteriorization remains the gold standard of treatment when there is any doubt. Rectal injury should be repaired when feasible and diverted and the presacral space drained. Distal rectal washout is of proven merit. Antibiotics provide an important adjunct to therapy. They should be initiated early (preoperatively), ended quickly (12 to 72 hours postoperatively), and provide a broad spectrum of coverage. The treatment of established infection should be guided by bacterial culture. Postoperatively, aggressive support is important for a good outcome. The significant incidence of complications even in the face of optimal management demands continued vigilance and aggressive intervention by the operating surgeon.

Vascular-Access Infections in Hospitalized Patients

Vascular catheters are a common source of nosocomial infections, although many of these infections are potentially preventable. A long duration of catheterization, multiple catheter manipulations, the inexperience of some inserters, use of transparent plastic dressings, violations of aseptic technique, the use of multilumen catheters, and inadequate sterilization of reusable pressure transducers all increase the risk of these infections. The only interventions that have been proved to reduce the risk are standardized insertion and maintenance technique by an intravenous-therapy team, preinsertion skin preparation with chlorhexidine gluconate, and the use of topical antibiotics at the insertion site. The goal of the physician should be to prevent catheter infection, because the treatment of established infection can be difficult and costly. Treatment must be individualized for each patient on the basis of the clinical presentation and the causative organism.

Single-dose prophylaxis for vaginal and abdominal hysterectomy

The practice of administering perioperative antimicrobials to uninfected patients undergoing elective surgical procedures has been subjected to careful prospective investigative scrutiny during the past two decades. A wound classification system was developed, helping to identify procedures for which prophylaxis did not provide benefit to the patient. Guidelines for prophylaxis in hysterectomy were proposed and risk factors were sought. Pharmacokinetics and spectrum of antibacterial activity, although variables of paramount importance in predicting success in the treatment of established infections, were discovered to have questionable impact on prophylactic efficacy. Duration of antimicrobial administration has gradually diminished from the total length of hospital stay to a single preoperative dose without increased risk of infection; efficacy may be related to route of administration. The wisdom of using newer agents for prophylaxis is addressed and questioned.

Role of granulocytes in the prevention and therapy of experimental Streptococcus sanguis endocarditis in rabbits.

The contributions of granulocytes to the prevention and therapy of Streptococcus sanguis endocarditis with procaine benzylpenicillin (PBP) was investigated in rabbits. Depletion of granulocytes by treatment with mechlorethamine appeared to have no significant effect on either the prophylactic or therapeutic activities of PBP. Administration of 3,000 IU of PBP before inoculation with S. sanguis retarded the course of the endocarditis for only 24 h whether granulocytes were normal or depressed in numbers. Prophylaxis with either 15,000 or 30,000 IU of PBP was equally effective in non-granulocytopenic and granulocytopenic rabbits. Treatment of established infections with PBP at doses of 3,000 to 300,000 IU of PBP at 12-h intervals for 48 h was equally effective in rabbits with normal and depressed numbers of granulocytes. The effect of 3,000 IU of PBP was equivalent, however, to that of granulocytes alone, as shown by the fact that the numbers of CFU per gram of vegetation in the granulocytopenic rabbits treated with this dose of PBP and in the non-PBP-treated control rabbits were not significantly different.

Rectal administration of metronidazole in severely ill patients.

Ten severely ill patients with life threatening sepsis received metronidazole as suppositories and blood concentrations of the drug were measured twice daily over five days. Therapeutic blood concentrations of metronidazole were maintained at all times in all patients. Rectal administration of metronidazole is accepted as effective prophylaxis against infection associated with surgery and as treatment of established infection. This study shows that in gravely ill patients metronidazole administered as suppositories gives perfectly adequate therapeutic serum concentrations of the drug, but that to achieve these concentrations rapidly the first suppository should be given with an intravenous loading dose.

USE OF PROPHYLACTIC ANTIBIOTICS IN SURGERY

A prospective survey of 352 surgical patients revealed that 52% (183 patients) were given antibiotic drugs perioperatively, (32% (111 patients) for prophylaxis and 20% (72 patients) for treatment of established infection). Prophylaxis was not reasonably indicated in only 24 patients, but there was little standardization of drug, dose, timing or duration of courses. The mean duration of prophylactic courses was six days; less than half began before operation. Thirty-two patients (11% of 283) developed an infection after operation; the incidence in patients with and without antibiotic prophylaxis was 17% (19/111) and 8% (13/172) respectively, but the former were, in general, higher risk subjects. Antibiotic use determines the emergence of resistant microorganisms and efficacy of prophylaxis is in the main unproven. Clearly, a carefully considered policy on antibiotic prophylaxis within an institution is a logical necessity yet to be realized.

Clavulanic acid and penicillin treatment of Staphylococcus aureus renal infection in mice

Clavulanic acid, an inhibitor of beta-lactamase, was used together with penicillin to treat infection caused by a penicillinase-producing Staphylococcus aureus. Clavulanic acid + penicillin administered to mice, prophylactically or in treatment of established infection, reduced morbidity, bacterial counts in the kidneys, and/or mortality; these differences were statistically significant when compared with those obtained by using penicillin or clavulanic acid alone.

The immediate use of antimicrobial agents

The use of antimicrobial agents in the surgical period is discussed with reference to the role of the anaesthetist in prophylaxis against the spread of infection in the patient, the treatment of established infection, the protection of the anaesthetist against infection from the patient and of the patient against the side-effects of the antimicrobial agents themselves.

Treatment of established infections of candidasis in partridges with formic acid.

Treatment of established infections of candidasis in partridges with formic acid.