Tetracyclines, chloramphenicol, erythromycin, and clindamycin

The tetracyclines are effective in the treatment of Chlamydia, Mycoplasma pneumoniae, and rickettsial infections and may also be used for gonococcal infections in patients unable to tolerate penicillins. These drugs may cause gastrointestinal irritation, photo-toxic dermatitis, diarrhea, vestibular damage, and hepatotoxicity in pregnant women. Chloramphenicol is used primarily for anaerobic infections, Haemophilus influenzae meningitis, and typhoid fever. The most important toxic effect of chloramphenicol is bone marrow suppression, which can be dose related or idiosyncratic. Erythromycin is the drug of choice for the treatment of infections caused by M. pneumoniae, Legionella species, group A beta-hemolytic streptococci, and Streptococcus pneumoniae. The frequency of serious untoward effects associated with the use of erythromycin is low; epigastric distress may occur. Clindamycin is active against Bacteroides fragilis and other anaerobic microorganisms. Pseudomembranous enterocolitis has developed in as many as 10% of patients taking this drug. The use of clindamycin should be discontinued promptly if diarrhea occurs.     

Erythromycin: a microbial and clinical perspective after 30 years of clinical use (2)

Erythromycin, first introduced for clinical use 30 years ago, was found to be effective for the treatment of gram-positive bacterial infections. Emergence of resistance and the advent of penicillinase-resistant penicillins limited the use of erythromycin for serious staphylococcal infections; however, erythromycin remains among the drugs of choice for the treatment of acne, infections of the skin and soft tissues, streptococcal pharyngitis, bronchitis, pneumonitis, diphtheria, carriers of pertussis, and, when administered with a sulfonamide, otitis media. Erythromycin is the drug of choice for the empiric treatment of outpatients with pneumonitis. Erythromycin is also the drug of choice for the treatment of Legionella pneumonia and is effective therapy for Chlamydia infections. Other uses of erythromycin include prophylaxis for elective colon operations and treatment of Campylobacter enteritis, genitourinary infections, and some sexually transmitted diseases.     

Effects of intravenous erythromycin lactobionate in respiratory infections

The antibiotic erythromycin lactobionate given intravenously acts almost exclusively on Gram-positive bacteria. Even at high plasma and tissue concentrations there is an almost total absence of side-effects. It could be considered, therefore, as first choice in the treatment of patients with infectious respiratory diseases. Most of the 40 patients admitted to the present study were elderly and all had either acute or chronic and becoming acute respiratory disease. Their clinical symptoms and levels of phlogosis improved on treatment with erythromycin lactobionate without any interruption of therapy due to side-effects and toxicity. The absence of unfavourable pharmacological interactions further enhances the usefulness of the drug. In view of the excellent response to monotherapy with erythromycin lactobionate and the few groups of resistant bacteria found in those cases when it was possible to check, it was not considered necessary to investigate any synergistic association with other antibiotics. It can be concluded, therefore, that therapy with erythromycin lactobionate in patients with infective respiratory disease is favourable and patients show excellent tolerability.     

The macrolides: erythromycin, clarithromycin, and azithromycin.

In addition to erythromycin, macrolides now available in the United States include azithromycin and clarithromycin. These two new macrolides are more chemically stable and better tolerated than erythromycin, and they have a broader antimicrobial spectrum than erythromycin against Mycobacterium avium complex (MAC), Haemophilus influenzae, nontuberculous mycobacteria, and Chlamydia trachomatis. All three macrolides have excellent activity against the atypical respiratory pathogens (C. pneumoniae and Mycoplasma species) and the Legionella species. Azithromycin and clarithromycin have pharmacokinetics that allow shorter dosing schedules because of prolonged tissue levels. Both azithromycin and clarithromycin are active agents for MAC prophylaxis in patients with late-stage acquired immunodeficiency syndrome (AIDS), although azithromycin may be the preferable agent because of fewer drug-drug interactions. Clarithromycin is the most active MAC antimicrobial agent and should be part of any drug regimen for treating active MAC disease in patients with or without AIDS. Although both azithromycin and clarithromycin are well tolerated by children, azithromycin has the advantage of shorter treatment regimens and improved tolerance, potentially improving compliance in the treatment of respiratory tract and skin or soft tissue infections. Intravenously administered azithromycin has been approved for treatment of adults with mild to moderate community-acquired pneumonia or pelvic inflammatory diseases. An area of concern is the increasing macrolide resistance that is being reported with some of the common pathogens, particularly Streptococcus pneumoniae, group A streptococci, and H. influenzae. The emergence of macrolide resistance with these common pathogens may limit the clinical usefulness of this class of antimicrobial agents in the future.     

Resolving the common clinical dilemmas of syphilis

The diagnosis and treatment of syphilis can present difficult dilemmas. Serologic tests can be negative if they are performed at the stage when lesions are present, and the VDRL test can be negative in patients with late syphilis. Cerebrospinal fluid examination is not required in patients with primary or secondary disease and no neurologic signs or symptoms, but it may be warranted in patients with late latent syphilis or in whom the duration of infection is unknown. Patients with penicillin allergy can be treated with alternative regimens if they have primary or secondary syphilis. Penicillin is the only effective drug for neurosyphilis; oral desensitization should be accomplished before treatment of penicillin-allergic patients. Other dilemmas may be encountered in the treatment of patients who have concurrent human immunodeficiency virus infection.     

Pneumonia. Patient profiles, choice of empiric therapy, and the place of third-generation cephalosporins.

Choosing appropriate antimicrobial therapy for patients with pneumonia requires knowledge of the etiologic agents seen in specific kinds of patients at specific times and places. For community-acquired pneumonia, there is an important difference in the agents seen in the normal and the compromised host. The normal host most often presents with viral, mycoplasmal, or pneumococcal pneumonia. The exact place of Chlamydia pneumoniae is still under study. A normal host who aspirates is at risk of anaerobic pneumonia. Normal hosts with influenza may acquire superinfection with Streptococcus pneumoniae, Haemophilus influenzae, or Staphylococcus aureus. Under specific epidemiologic conditions, community-acquired pneumonia may be due to Legionella species, Yersinia pestis, Francisella tularensis, Coxiella burnetii, Chlamydia psittaci, a mycotic agent, or tuberculosis. Patients with chronic bronchitis and emphysema are predisposed to H. influenzae, Moraxella catarrhalis, and S. pneumoniae infections. HIV-infected patients are likely to have Pneumocystis carinii pneumonia and pneumonia due to cytomegalovirus, S. pneumoniae, and H. influenzae. Patients with diabetes, nursing-home patients, hospitalized patients, immuno-compromised patients, and patients with recent antibiotic therapy are predisposed to pneumonia due to Gram-negative aerobic bacilli of enteric and environmental origin. Initial therapy should be directed at the likely organism or organisms based on hospital susceptibility surveillance. In the normal host with community-acquired pneumonia, the therapy will often be penicillin G or erythromycin. In the patient predisposed to Gram-negative pneumonia, a third-generation cephalosporin with or without an aminoglycoside is the usual choice.     

Patients' choice of asthma and allergy treatments

BACKGROUND AND OBJECTIVES: Only a few studies have focused on a comparison between general practitioner (GP) patients' and classical homeopath (CH) patients' reasons for choosing, continuing or termination of their treatment by GPs or CHs, respectively. The existing studies are mostly based on quantitative methods and dealing with patients' reasons for choosing complementary and alternative medicine (CAM). The objective of this paper is to develop concepts to understand and compare Danish GP patients' and CH patients' initial choice of, continuing choice of, and termination of treatments for asthma and allergy. DESIGN: Data originate from an explorative study based on semistructured interviews with 18 GP patients and CH patients having asthma and allergy. The selection of the patients to the interviews was based on a questionnaire study including 88 respondents (response rate 58 patients). RESULTS: In understanding the patients' initial choice and continuing choice of treatment and termination of treatment, the concepts push-from, pull, press-into, stop, and stay factors are used. These factors are connected to the patients' experiences with conventional treatment, patients' attitudes toward and personal experiences with alternative treatment, and the patients' understanding of their asthma and allergy. The results of the study indicate that patients before seeking CHs had experienced inappropriate health care within the conventional health care system. The results of the study also indicate that if the CH patients experience inappropriate health care within homeopathic treatment, they terminate the treatment. CONCLUSIONS: The study indicates the importance of health providers' insight into GP patients' and CH patients' different reflections on adverse events, the patients' different understandings of asthma and allergy, and the different learning processes that GP patients and CH patients might be involved in while living with asthma and allergy. These are important issues for understanding patients' initial and, continuing choice of and termination of GP treatment and CH treatment, respectively.     

Comparative in vitro activity of garenoxacin against Chlamydia spp

The in vitro susceptibilities of 33 isolates of Chlamydia trachomatis, Chlamydia pneumoniae and Chlamydia psittaci to a new quinolone drug, garenoxacin (BMS-284756), in comparison with levofloxacin, ciprofloxacin, doxycycline, erythromycin and roxithromycin, were determined. Garenoxacin was the most active of the quinolone drugs tested, with identical MIC and MBC, which ranged from 0.007 to 0.03 mg/L. The MIC and MBC of the other two quinolones tested, levofloxacin and ciprofloxacin, were also identical, ranging from 0.25 to 2 mg/L. The MICs and MBCs of doxycycline, erythromycin and roxithromycin were also determined.     

In vitro susceptibility of recent clinical isolates of Chlamydia trachomatis to macrolides and tetracyclines

We tested the in vitro activity of clarithromycin, azithromycin, roxithromycin, erythromycin, doxycycline, and tetracycline against 50 clinical isolates of Chlamydia trachomatis. The minimal inhibitory concentrations (MICs) and the minimal bactericidal concentrations (MBCs) were determined in a tissue culture system using cycloheximide treated McCoy cells. MIC values for all the isolates were < or =0.015 microg/ml for clarithromycin, < or =0.125 microg/ml for roxithromycin and azithromycin, and < or =0.25 microg/ml for erythromycin and doxycycline. Almost half of the isolates (44%) were inhibited only by a concentration of 0.5 microg/ml of tetracycline. MBC as high as 4 microg/ml was displayed by doxycycline and tetracycline against 8% and 4% of the isolates respectively of the agents recommended by the Center for Disease Control as drugs of choice for the treatment of chlamydial infections, azithromycin exhibited a markedly better in-vitro activity than did erythromycin and doxycycline.     

Cholestasis and liver cell damage due to hypersensitivity to erythromycin stearate--recurrence following therapy with erythromycin succinate

Erythromycin is a frequently used antibiotic in patients with atypical respiratory infection and/or an allergy to penicillin. We report the case of a young woman who developed severe cholestasis and jaundice following treatment with erythromycin stearate. Two years later her general practitioner prescribed erythromycin succinate for pharyngitis. She experienced a severe second episode of jaundice and malaise. Different esters of erythromycin have been introduced to reduce side effects such as allergic reactions to erythromycin. The findings in our patient underline the fact that hypersensitivity is caused by the erythromycin molecule, independent from the type of esterification. Because of these side effects newer makrolides should be given preference over erythromycin.     

Medicating young or very young patients--part II

Having a sick child can be stressful for parents, even if the illness is a mild cold or gastrointestinal upset. Part of that stress may be related to uncertainty about when to seek professional help and when to choose an over-the-counter (OTC) medication. When choosing to use an OTC medication, parents are faced with another uncertainty-which agent to use. The variety of available agents, many with pictures of children on the labels or names that indicate "for children" makes a wise choice challenging. Knowledgeable nurses, who interact with sick children and their parents in any setting, can do much to relieve some of this uncertainty and stress by talking to parents about the treatment and medication choices they make. In the following discussion, examples of medications used to treat common problems in younger patients are discussed. Contraindications, safety concerns, potential drug-drug interactions, and safe administration guidelines are identified for each example. Part III of this series will address examples of medications used to treat more complicated childhood problems, such as asthma, allergy, attention-deficit disorders, and obesity.     

Tetracyclines, chloramphenicol, erythromycin, clindamycin, and metronidazole.

The tetracyclines are effective in the treatment of Chlamydia, Mycoplasma pneumoniae, and rickettsial infections and also can be used for gonococcal infections in patients unable to tolerate penicillin. These drugs may cause gastrointestinal irritation, diarrhea, phototoxic dermatitis, and vestibular damage, and fatal reactions due to hepatotoxicity have occurred in pregnant women. Chloramphenicol has a broad spectrum of bacteriostatic activity, but its association with suppression of the bone marrow and aplastic anemia has relegated it to a historical role. Erythromycin is the drug of choice for the treatment of infections caused by M. pneumoniae, Legionella species, group A beta-hemolytic streptococci, and Streptococcus pneumoniae. The frequency of serious adverse effects associated with the use of erythromycin is low; dose-related epigastric distress may occur. Clindamycin is bactericidal to most nonenterococcal gram-positive aerobic bacteria and many anaerobic microorganisms. Although historically it was a frequent cause of antibiotic-associated diarrhea and colitis, clindamycin is considered an excellent alternative to beta-lactam antibiotics for treatment of many staphylococcal infections, and it has therapeutic utility in anaerobic infections and in several protozoan infections in immunosuppressed patients. Metronidazole is efficacious for treating nonpulmonary anaerobic infections, various parasitic infections (trichomoniasis, amebiasis, and giardiasis), nonspecific vaginitis, and Clostridium difficile-mediated colitis. With use of metronidazole, mild side effects such as epigastric discomfort, diarrhea, reversible neutropenia, and allergic-type cutaneous reactions may occur.     

Chlamydial infections. Gaining control of a growing epidemic

Infections caused by Chlamydia trachomatis are wide-spread, costly, and damaging. Consequences are harshest for women because of the adverse effects on the reproductive system. Newborns of infected mothers may also be affected. Screening of sexually active patients is important, because many infected patients are asymptomatic. Newer, improved laboratory techniques are available. Treatment with doxycycline, tetracycline, or erythromycin is preferred. Simultaneous treatment of sexual partners is vital.     

The in-vitro antibiotic susceptibility of Chlamydia pneumoniae

A cell culture technique was used to test the in-vitro susceptibility of the type strain of Chlamydia pneumoniae to 23 antibiotics including macrolides, tetracyclines and quinolones. The activity of the antibiotics tested was similar to previous findings with C. trachomatis. Clarythromycin had the lowest MIC overall (0.007 mg/l). Other macrolides were found to have similar MICs to erythromycin (0.06 mg/l). Both the macrolides and the tetracyclines were more active than the quinolones. It is proposed that the tetracyclines and erythromycin should be the drugs of choice for treating infections with C. pneumoniae; however several other antibiotics need to be evaluated.     

Therapy for heart failure

The treatment of congestive heart failure focuses on three steps: 1. Elimination of the precipitating cause or mechanism, and/or treatment of the underlying disease respectively. 2. Treatment of the failing heart syndrome itself. We shall concern ourselves with pharmacotherapy, omitting technical and surgical aspects. 3. Prophylactic treatment of complications, such as thromboembolism and arrhythmias. Drugs for the treatment of heart failure can be classified as follows: 1. Diuretics 2. Vasodilators 3. Neurohumoral Inhibitors 4. Inotropic drugs. Diuretics improve symptoms and exercise capacity and probably survival. They are the drug of first choice in acute and chronic heart failure. Potassium supplementation is necessary. Renal function needs to be monitored. The aldosterone antagonist spironolactone has probably important effects upon the myocardium. It retards fibrous tissue development and improves prognosis. Vasodilators unload the heart and improve contractile geometry and hemodynamics, thereby lessening symptoms. Prognosis, however, is not affected. They are indispensable in acute heart failure. In longterm treatment only the combination of nitrates with hydralazin has been shown to be effective. Angiotensin converting enzyme inhibitors combine vasodilation with neurohumoral inhibition. They are most effective in improving symptoms, exercise capacity and surviving chronic heart failure. If side effects (cough, allergy) prevent their use, then angiotensin II receptor antagonists can be used with equal benefit. However, both groups of drugs impair renal function and cannot be given in advanced renal failure or renal artery stenosis. Beta-receptor antagonists, previously considered contraindicated in heart failure are today amongst the most important drugs in heart failure. They improve survival and retard the need for cardiac transplantation in advanced failure. Their use, however, is rather difficult requiring extremely slow dose titration beginning with very low doses. Inotropic drugs are today mainly used in acute failure and cardiogenic shock. In longterm treatment only the digitalisglycosides have been shown to be effective in improving symptoms, exercise capacity and the general clinical course. Often antiarrhythmic treatment is necessary. Here amiodarone is the drug of choice today if beta blockers do not suffice. Prophylactic anticoagulation is indicated in all cases NYHA III and IV, with large hearts already in II. Future developments may include new inotropes, the ANP-system, and cytokines, as well as gene therapy for correction of myocardial phenotype change.     

Allergy shots for hay fever

Although allergy shots have been used for many years, immunotherapy for symptoms of allergic rhinitis has only recently been clearly shown to be effective. Standardization of allergens will provide even better results in the diagnosis and treatment of allergic rhinitis in the future. Success in an individual patient depends on appropriate application. Immunotherapy should be reserved for patients who have allergy to airborne allergens, have significant symptoms after exposure to them, have sensitivity that has been proven by a skin or in vitro test, and cannot avoid the allergen or control symptoms with drugs. Thus, allergy shots are generally not used for allergy to pet dander or food. Immunotherapy is begun with a very dilute concentration of allergen, which is gradually increased to the maximum dose that is safely tolerated. The interval between shots is then increased gradually to once a month. Duration of treatment is usually 3 years in children and longer in adults. Treatment usually fails if the patient cannot free the environment of large amounts of known allergens, if the allergen was not correctly determined during initial evaluation, or if the allergen dose is inadequate. The patient must have realistic expectations: Allergy shots often do not totally eliminate symptoms, and improvement takes time.     

In vitro drug susceptibility of Chlamydia sp. strain TWAR.

The in vitro susceptibilities of eight Chlamydia sp. strain TWAR isolates were tested against tetracycline, erythromycin, penicillin, ampicillin, sulfisoxazole, and a new drug, trospectomycin. The ranges of inhibitory concentrations of these antimicrobial agents, except for sulfonamide, were similar to those for Chlamydia trachomatis. Sulfisoxazole was not inhibitory at the highest nontoxic concentration tested.     

Automatic Implantable Cardioverter Defibrillator: Cost Effectiveness

Unexpected out-of-hospital cardiac arrest is in most cases due to ventricular fibrillation or rapid ventricular tachycardia. The usual therapeutic strategy in survivors starts with drug treatment, in case of failure followed by nonpharmacological therapy, which may include catheter ablation, ablative surgery, and finally defibrillator implantation. In most cases, this strategy is long lasting and very expensive. Implantation of a defibrillator as a first choice therapy may be cost effective, especially if the probability of successful drug treatment is low. However, cost-effective aspects have been studied only retrospectively and in models. In 1989 we started a prospective cost-effectiveness analysis of implantation of the automatic implantable cardioverter defibrillator (AICD) as first choice therapy ("early" AICD implantation) in successfully resuscitated postinfarct patients. Evaluation is being done in a randomized way with one group having early AICD implantation and the other group following the usual conventional therapeutic strategy. We compare medical, economic, and quality-of-life aspects. As of June 1992, 46 patients have entered the study. Totally 60 patients will be included. Results are expected in 1993 and will be expressed as cost effectiveness ratios in both study arms.     

Current perspectives on the perioperative management of the latex-allergic patient

The increasing incidence of latex allergy necessitates thorough preanesthetic screening for risk factors, which will be delineated in this article, that are associated with latex allergy. The pathophysiology, epidemiology, and testing procedures for latex allergy will be reviewed. This case report will illustrate the management of a patient who was found to be latex-sensitive during surgery and the management of intraoperative anaphylaxis is provided. Safe perioperative care can be provided for latex-sensitive patients if latex avoidance techniques are used consistently.     

Characterization of erythromycin resistance in Campylobacter jejuni and Campylobacter coli.

The mechanism of resistance to erythromycin, the drug of choice in the treatment of campylobacter gastroenteritis, was investigated. Erythromycin resistance (MICs, greater than 1,024 micrograms/ml) in three clinical isolates of Campylobacter jejuni and one C. coli isolate was determined to be constitutive and chromosomally mediated. In vivo protein synthesis in erythromycin-susceptible C. jejuni and C. coli strains was completely inhibited by low levels of erythromycin (5 micrograms/ml), whereas a high concentration of the antibiotic (100 micrograms/ml) had no effect on protein synthesis in erythromycin-resistant strains. Biological assays showed that extracellular degradation of erythromycin was not responsible for erythromycin resistance in strains of Campylobacter species. The rates and amounts of uptake of [14C]erythromycin by resistant and susceptible campylobacter cells were determined to be similar. Binding assays with purified campylobacter 70S ribosomes as well as 50S ribosomal subunits showed that those from erythromycin-resistant strans bound much less [14C]erythromycin than did those from susceptible strains. Genomic DNA from C. coli UA585 was used to transform erythromycin resistance to C. coli UA417. The erythromycin resistance marker was associated with a 240-kb SmaI fragment of the C. coli UA585 genome. Our results rule out erythromycin inactivation or efflux and are not consistent with the production of an RNA methylase, although they are consistent with a mutational mechanism of resistance due to a change in a ribosomal protein gene. This study constitutes a detailed biochemical and genetic characterization of erythromycin resistance in Campylobacter species.