Quantification of HIV-1 virus load under zidovudine therapy in patients with symptomatic HIV infection: relation to disease progression.

OBJECTIVE: To measure changes in HIV-1 virus load following zidovudine therapy, and to investigate the relationship between these changes and clinical progression. DESIGN: Prospective study of 18 symptomatic, zidovudine-naive patients, with CD4 count < 350 x 10(6)/l. METHODS: The following parameters were measured at each visit, before zidovudine therapy, after 1 month of therapy, and every 3 months thereafter. HIV-1 virus load in peripheral blood was determined by serum immune complex-dissociated HIV-1 p24 antigen (ICD-p24 Ag), quantitative plasma and cellular viraemia. A virologic response under zidovudine was defined as > 50% decrease in ICD-p24 Ag levels or > 1 log10 decrease in plasma or cellular viraemia titres from baseline values. CD4 and CD8 cell counts, and beta 2-microglobulin levels were also measured. Disease progression was defined as the time to a new AIDS-defining event or death. RESULTS: At enrolment, 13 out of 18 (72%) patients had positive ICD-p24 Ag and positive plasma viraemia, with a mean of 44 median tissue culture infective dose (TCID50) per ml; all patients had positive cellular viraemia with a mean TCID50 of 230 per 10(6)/l cells. Median CD4 cell count was 43 x 10(6)/l. Ten patients developed a new AIDS-defining event and eight died during a median follow-up of 15 months on zidovudine. Baseline prognostic markers for development of a new AIDS-defining event included ICD-p24 Ag, CD4 and CD8 cell counts, but only CD4 cell count remained predictive on multivariate analysis (P = 0.003). When each laboratory marker was analysed as a time-dependent covariate, only CD4 (P = 0.002) and CD8 (P = 0.001) cell counts predicted the occurrence of a new AIDS-defining event. Eight out of 13 (61.5%) patients had an ICD-p24 Ag response, and seven out of 13 (54%) a plasma viraemia response, but only cellular viraemia responders (five out of 18; 28%) had a 5.6-fold decrease in their risk of developing an AIDS-defining event (90% confidence interval, 1-33; P = 0.05). None of these markers correlated with survival. CONCLUSIONS: Plasma viraemia and ICD-p24 Ag, while providing useful short-term markers of zidovudine antiviral activity in vivo, do not correlate with disease progression in patients with advanced HIV infection. CD4 cell count remained the best initial and time-dependent predictor for development of new AIDS-defining events. Interestingly, a high CD8 cell count and a decrease in cellular viraemia titres also appear to be predictive of improved clinical outcome in this population.

Sulfadiazine-induced crystalluria in AIDS patients with toxoplasma encephalitis.

Toxoplasma encephalitis is the most common opportunistic infection of the central nervous system in patients with AIDS. The treatment of choice is a combination of sulfadiazine and pyrimethamine. We present here four patients with AIDS treated for toxoplasmic encephalitis who developed sulfadiazine-induced crystalluria. This complication was rapidly reversible with rehydration and urine alkalinization. Patients with AIDS treated with high doses of sulfadiazine should be adequately hydrated, and their urinary pH maintained above 7.5 to prevent sulfadiazine-induced crystalluria.

Risk factors for Clostridium difficile-associated diarrhoea in HIV-infected patients.

OBJECTIVE: To identify risk factors associated with a first episode of Clostridium difficile-associated diarrhoea (CDAD) in patients with HIV infection. DESIGN: A case-control study. SETTING: University teaching hospital HIV inpatient unit. PATIENTS AND METHODS: Nineteen HIV-infected patients with CDAD, defined as diarrhoea with positive stool culture for Clostridium difficile (CD) and positive stool cytotoxin B assay, were compared with 38 randomly selected controls (HIV-infected patients hospitalized on the ward on the day the matched case was diagnosed). CD isolates were phenotyped by electrophoretic protein patterns. RESULTS: The incidence of CDAD among HIV-infected patients was 4.1/100 of patient-admissions. On univariate analysis, cases were more likely to have used clindamycin [11 out of 19 compared with four out of 38; odds ratio (OR) 19; 95% confidence interval (CI), 2-160; P = 0.0007], and pyrimethamine (14 out of 19 compared with 13 out of 38; OR, 4.8; 95% CI, 1.4-16, P = 0.02) in the month before diagnosis, and to have had cerebral toxoplasmosis (12 out of 19 compared with 13 out of 38; OR, 2.8; 95% CI, 0.9-8.6; P = 0.09). There was also a significant increase of the risk of CDAD as duration of hospitalization in the ward increased (chi 2 for trend, P = 0.007). Multivariate models associated two risk factors with CDAD: clindamycin use (OR, 42; 95% CI, 2-813; P = 0.01), and prolonged hospitalization in the ward (OR, 3.6 per week in the ward; 95% CI, 1-13, P = 0.048). Of 18 available CD isolates, 15 (83%) had identical electrophoretic protein pattern. CONCLUSIONS: Clindamycin use and prolonged hospitalization in the ward were the main risk factors associated with CDAD in this study. These observations, together with the occurrence of one major phenotype of CD, suggest nosocomial transmission of CD in the ward.

Diagnosis of infections caused by Enterocytozoon bieneusi and Encephalitozoon intestinalis using polymerase chain reaction in stool specimens.

OBJECTIVE: To study the usefulness of polymerase chain reaction (PCR) for the species identification of microsporidia in stool specimens obtained from HIV-infected patients with Enterocytozoon bieneusi or Encephalitozoon intestinalis infections. SETTING: Infectious disease clinic in a university hospital. PATIENTS: Thirty-seven stool specimens from 29 HIV-infected patients with microsporidiosis were tested. The diagnosis of microsporidian infection was made by light microscopy of stool specimens and species identification was made by transmission electron microscopy of duodenal biopsies. Sixty-one stool specimens from 45 HIV-infected patients without microsporidiosis served as controls. METHODS: PCR was performed using DNA extracted from stools with two primers sets, one specific for E. bieneusi and one specific for E. intestinalis. RESULTS: A 1265 base-pair fragment of the small subunit ribosomal RNA (rrs) gene could be amplified from all 31 stool specimens infected with E. bieneusi. In addition, a 930 base-pair fragment of the rrs gene could be amplified from all six stool specimens infected with E. intestinalis. The 61 control stools were negative with both primers. CONCLUSIONS: These results suggest that a PCR based assay using species-specific primers sets can be used successfully for microsporidian species differentiation from stool specimens, thus obviating the need for invasive biopsy procedures.

Impact of protease inhibitors on AIDS-defining events and hospitalizations in 10 French AIDS reference centres. Fédération National des Centres de Lutte contre le SIDA.

OBJECTIVE: To assess the clinical and economic consequences of the use of protease inhibitors in the treatment of HIV infection. DESIGN: Multicentric, observational, retrospective cohort study. SETTING: Ten AIDS reference centres in France. PATIENTS: All patients followed in each centre from September 1995 through October 1996. MAIN OUTCOME MEASURES: AIDS-defining events, death, health-care resources use, administration of antiretroviral therapy. RESULTS: Data from 7749 patients in 10 centres showed a drop in hospitalization days by 35%, new AIDS cases by 35%, and deaths by 46%. In the same period, the proportion of patients receiving antiretrovirals rose from 36 to 53% including highly active antiretroviral therapy (HAART), which rose from 0.3 to 18%. Overall cost evaluation showed a slight increase of monthly treatment cost of US$ 12 per patient. Comparison of the three centres that used HAART earliest to the three centres that used it latest showed a clear benefit to early HAART with a drop in hospitalization days by 41%, new AIDS cases by 41% and deaths by 69%. The proportion of patients with HAART rose to 27% and monthly health-care cost decreased by US$ 248852 (i.e., by US$ 101 per patient per month). Late prescribing centres experienced a less marked effect with a drop in hospitalization days by 22%, new AIDS cases by 31%, and deaths by 32.5%. Proportion of patients with HAART rose to 12% and monthly health-care costs increased by US$ 113578 (i.e., by US$ 38 per patient per month). CONCLUSIONS: This study supports the extensive use of HAART in HIV-infected patients.

Campylobacter infections in HIV-infected patients: clinical and bacteriological features.

OBJECTIVE: To study the clinical and bacteriological features of Campylobacter infections in HIV-infected patients. DESIGN: A retrospective analysis (1989-1992), followed by a prospective analysis (1992-1994). SETTING: Hospital HIV inpatient unit. PATIENTS AND METHODS: All patients with Campylobacter spp. identified by the laboratory of microbiology at Saint-Louis Hospital, Paris were studied, and their clinical features as well as their response to therapy recorded. RESULTS: During the study period, Campylobacter infection was documented in 38 HIV-infected patients, 76% of whom had AIDS. Campylobacter spp. was isolated from stools in 36 cases and from blood cultures in four cases. Species identification yielded C. jejuni (84%) and C. coli (16%). High-level resistance to quinolones was frequently observed (21%), but resistance to erythromycin (3%) and tetracycline (5%) was rare. Diarrhoea, fever and abdominal pain were the main clinical features of infection. Other intestinal pathogens were found in 42% of patients. Most patients had an acute illness with rapid resolution under appropriate antimicrobial therapy. However, eight patients (21%), experienced chronic diarrhoea with persistent isolation of Campylobacter and in vivo selection of resistant strains, requiring multiple courses of antibiotics. CONCLUSIONS: Campylobacter usually cause acute diarrhoea in patients with HIV infection. Antimicrobial therapy should be guided on in vitro susceptibility testing because of the prevalence of antibiotic resistance. Despite appropriate therapy, some patients will present with prolonged diarrhoea and in vivo selection of multiresistant isolates.

Potential efficacy of fumagillin in intestinal microsporidiosis due to Enterocytozoon bieneusi in patients with HIV infection: results of a drug screening study. The French Microsporidiosis Study Group.

OBJECTIVE: Intestinal microsporidiosis due to Enterocytozoon bieneusi is a frequent cause of chronic diarrhoea in patients with HIV infection for which there is no available therapy. This study was designed to search for a drug with activity against this organism. DESIGN: Prospective open-labelled Phase II multicentre study. SETTING: University hospitals. PATIENTS: Sixty HIV-infected men with intestinal E. bieneusi infection. INTERVENTIONS: Ten drug regimens were consecutively tested orally for 3 weeks: albendazole plus metronidazole, sulphadiazine plus pyrimethamine, atovaquone, doxycycline plus nifuroxazide, itraconazole, flubendazole, chloroquine, paromomycin, sparfloxacin and fumagillin. Nine evaluable patients per regimen were required, but each patient could be enrolled up to three times in the study. OUTCOME MEASURE: Efficacy was assessed primarily by the clearance of E. bieneusi from stools and intestinal biopsies. The safety of each regimen was also assessed. RESULTS: Only purified fumagillin was able to clear E. bieneusi from stools as well as intestinal biopsies, whereas all other regimens failed to show antiparasitic efficacy. However, only four patients received fumagillin because of drug-induced thrombocytopenia. The four patients who received fumagillin remained free of E. bieneusi infection after a mean follow-up of 10 months. CONCLUSION: Eradication of E. bieneusi from the intestinal tract of patients with HIV infection and persistent immunosuppression is an achievable goal. Our study allowed the identification of oral fumagillin as a potential treatment for intestinal microsporidiosis due to E. bieneusi.

Cerebral tuberculosis in patients with the acquired immunodeficiency syndrome (AIDS). Report of 6 cases and review.

Cerebral tuberculosis (TB) was diagnosed in 6 (4%) of 156 HIV-infected patients with TB seen at our institution over 6 years. We describe here the clinical and radiologic features of these cases and of 15 others reported in the literature. Of the 21 patients, 59% were intravenous drug users. Presenting symptoms were fever (76%), confusion (52%), seizures (38%), and headache (38%). Fourteen patients (66%) had previous or active extracerebral TB at presentation. Cranial CT scan showed ring-(62%) or nodular-(24%) enhancing lesions or mixed forms (14%). Among the 12 patients who underwent a brain biopsy, bacteriologic evidence of TB was found in 9. Four patients (19%) died during hospitalization. Among the 17 others who received antituberculous therapy, only 1 developed neurologic sequelae. Five patients also received steroid therapy to control cerebral edema or paradoxical growth of the cerebral mass lesions. TB should be considered as a cause of cerebral mass lesions in HIV-infected patients, especially if tuberculous infection is suspected at other sites.

Empiric therapy of severe infections in adults.

The third-generation cephalosporins are useful for empiric therapy of most of the severe infections in adults as a result of their broad spectrum of antimicrobial activity (particularly against clinically important gram-negative bacteria), good tissue penetration, and lack of serious adverse effects. This review examines their use in respiratory tract infections, bacterial meningitis, skin-structure infections, and urinary tract infections in adult patients. Penicillin G remains the optimal therapy for severe community-acquired pneumonia, since Streptococcus pneumoniae still accounts for the majority of cases. However, for empiric treatment of nosocomial pneumonia, therapy must ensure coverage both of aerobic gram-negative bacilli and Staphylococcus aureus. The choice of empiric antibiotic therapy in the treatment of urinary tract infections depends on the pattern of resistance in the patient's environment. At present, the treatment of bacterial meningitis in otherwise healthy adults does not constitute a major problem provided that penicillin resistance among pneumococci and meningococci (responsible for at least 80 percent of cases) does not become a clinical problem. However, in meningitis in which gram-negative bacilli are suspected and where specific problems include antibiotic resistance among these organisms and the inadequate penetration of many antibiotics into the cerebrospinal fluid, third-generation cephalosporins are the drugs of choice, and they have markedly improved the clinical outcome. Most skin-structure infections are due to S. aureus and are best treated by an anti-staphylococcal penicillin or an older cephalosporin. Nevertheless, the third-generation cephalosporins have proved to be highly effective agents for infections of skin and soft-tissue infections associated with both gram-positive and gram-negative pathogens in patients at risk from these organisms or in the elderly.

Treatment of serious infections with intravenous ciprofloxacin. French Multicenter Study Group.

Ninety-four patients, 61 men and 33 women with a mean age of 54 years, were treated with intravenous ciprofloxacin. Eighty-one patients (86 percent) were in serious or fair condition. Pathogens included Enterobacteriaceae (74 patients), Pseudomonas sp. (23 patients), other gram-negative bacilli (five patients), staphylococci (19 patients), other gram-positive cocci (seven patients), and Rickettsia conorii (five patients). Thirty-eight patients were given parenteral therapy (ciprofloxacin at a mean daily dose of 200 mg every 12 hours, mean duration of therapy, nine days). Fifty-six patients were also given ciprofloxacin orally after initial intravenous therapy at a dose of either 500 or 750 mg every 12 hours (mean duration of therapy, 36 days). Another antibiotic was given concomitantly in 25 cases (27 percent). The overall clinical response was 93 percent and the bacteriologic response rate was 84 percent. There was no difference between patients treated by intravenous ciprofloxacin and those treated by intravenous ciprofloxacin followed by oral ciprofloxacin. Favorable responses (resolution of improvement) were observed in 39 of 42 patients (93 percent) with bacteremia, 28 of 30 (93 percent) with urinary tract infection, 10 of 13 (77 percent) with respiratory tract infection, 11 of 12 (92 percent) with bone and joint infection, three of three (100 percent) with skin and soft-tissue infection, nine of nine (100 percent) with intra-abdominal infection, three of three (100 percent) with typhoid fever, and two of two (100 percent) with meningitis. All five patients with R. conorii infections had a response to therapy. The adverse effects were minor and transient. Seven patients experienced clinical adverse effects: pain at the injection site (three patients), rash (two patients), and headache (2 patients). Serum transaminase levels were increased in 11 patients. Intravenously administered ciprofloxacin or intravenous ciprofloxacin followed by oral ciprofloxacin is a safe and effective therapy for serious infections.

Pulmonary Mycobacterium avium complex disease without dissemination in HIV-infected patients.

Pulmonary disease due to Mycobacterium avium complex (MAC) without evidence of dissemination is uncommon in HIV-infected patients. Five cases were observed over a 2-year period. All patients had AIDS and the median CD4 cell count at the time of presentation was 90 x 10(6)/L. Radiographic patterns included unilobar alveolar infiltrates or diffuse alveolar densities. All patients had a favorable clinical response to antimycobacterial chemotherapy with a median follow-up period of 10 months. MAC should be considered in HIV-infected patients with positive respiratory samples for acid-fast bacilli and pulmonary infiltrates. Patients with such findings in whom presumptive therapy for tuberculosis has failed should receive broad-spectrum antimycobacterial chemotherapy until final identification is available.

Detection by PCR of Toxoplasma gondii in blood in the diagnosis of cerebral toxoplasmosis in patients with AIDS.

The polymerase chain reaction (PCR) for amplification of Toxoplasma gondii DNA was performed prospectively in the blood of 19 patients with AIDS and cerebral toxoplasmosis. The B1 gene and TGR1E sequence were used as targets and results were confirmed by hybridisation. Controls consisted of 24 HIV infected patients with tissue culture proven T gondii parasitaemia and 57 HIV infected patients without toxoplasmosis. PCR was positive with both targets in 20 of 24 samples (84%) from patients with parasitaemia. Three of 57 samples (5%) from patients without toxoplasmosis were PCR positive with either target, but none was positive with both targets. Only three of the 19 patients (16%) with cerebral toxoplasmosis had a positive PCR with both targets before the start of specific treatment. PCR performed in blood is of little diagnostic value in cases of cerebral toxoplasmosis but could be useful in patients with disseminated infection.

Diffusion of 3-quaternary ammonium cephem antibiotics into cerebrospinal fluid of patients with bacterial meningitis.

Cefepime and cefpirome are new beta-lactamase resistant parenteral cephalosporin derivatives whose spectrum of activity makes them suitable for use in the treatment of severe infections such as bacterial meningitis. However, the published information on the penetration of these new agents into human CSF and on their use in the treatment of bacterial meningitis are really scarce. Experimental studies have shown that cefepime and cefpirome penetrated remarkably well into the CSF of animals infected with Streptococcus pneumoniae, Streptococcus agalactiae, Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Haemophilus influenzae type b or Pseudomonas aeruginosa. The mean changes in bacterial colony count in CSF after cefpirome or cefepime administration express the antibacterial activity of these drugs. Studies in patients show that cefepime and cefpirome crossed the blood-brain barrier and reached concentrations in the CSF that are bactericidal against most potential pathogens. Higher levels are likely to be achieved with multiple dosing and in the presence of inflamed meninges. No study has been performed to investigate the efficacy of cefpirome in the treatment of bacterial meningitis. Cefepime was as effective and safe as cefotaxime for treatment of patients with bacterial meningitis as shown in the only clinical trial.

High-dose intravenous fluoroquinolones in the treatment of severe infections.

A bacterial infection should be considered "serious" in case of underlying disease, nosocomial origin, antibiotic resistant pathogen, and/or poor delivery of antibiotics at the site of infection. Treatment of most serious infections requires parenteral administration of antimicrobial agents. Intravenous fluoroquinolones are a class of antimicrobial agents from which physicians must choose when treating nosocomial infections. Fluoroquinolones are bactericidal antimicrobial agents that act by inhibiting DNA gyrase. They are active in vitro against most gram-negative bacteria and methicillin-susceptible staphylococci. Activity against anaerobic bacteria and streptococci is poor. The rapid development of bacterial resistance in centers with high quinolone usage is of great concern. Resistance develops most commonly in Pseudomonas aeruginosa and staphylococci. Most clinical trials with ciprofloxacin, ofloxacin, pefloxacin, the fluroquinolones currently available in France for parenteral use, are almost 10 years old. There are few studies with higher dosage and most of them have been carried out with ciprofloxacin. The findings of these studies indicate that higher dosage regimens of i.v. ciprofloxacin are much more effective against severe nososcomial infections than is the dosage of 200 mg twice daily. The higher dosage regimens resulted in greater rates of clinical cure and improvement in both monomicrobial and polymicrobial infections. Although the overall frequency of side effects to fluoroquinolones is low, seizures and allergic reactions have been attributed to their use.

[Role of invasive candidiasis in hospital pathology]. / Place des candidoses invasives en pathologie hospitalière.

The frequency, mode of occurrence, diagnostic criteria and main features of systemic and visceral candidiasis have been evaluated in a retrospective study of all cases managed in St Louis Hospital, Paris, during the [June 1, 1985-May 31, 1986] period. During this one year period 23 patients suffered from systemic or visceral candidiasis and Candida spp. accounted for 9.6% of all positive blood cultures, fourth in number after Enterobacteriaceae, Staphylococcus and Pseudomonas. Abnormal underlying condition was present in all patients, mainly haematologic malignancies, serious abdominal surgery and AIDS. In patients with haematologic malignancies C. tropicalis was the main species involved in contrast with surgical patients in whom the dominant responsible species was C. albicans. No Candida oesophagus was common. Therapeutic regimens included amphotericin B in all patients with systemic disease. We conclude that in an institution mainly oriented toward management of cancer and surgical patients, systemic and visceral candidiasis are common and represent a serious problem.

[Pefloxacin: evaluation and clinical prospects]. / Péfloxacine: bilan et perspectives cliniques.

Following a summary of the main bacteriological and pharmacokinetic properties of this new quinolone derivative, the author reviews the results obtained with pefloxacine in the treatment of urinary tract infection, gonococcal urethritis, and bronchopulmonary, surgical, gynaecological, bone, soft tissue, neuromeningeal and ENT infections.

[Empirical antibiotic therapy and ceftazidime]. / Antibiothérapie empirique et ceftazidime.

Ceftazidime is indicated mainly for the empirical treatment of severe infections treated in hospital and of hospital-acquired infections. It can be used alone in numerous severe infections and it offers a good alternative to aminoglycosides and antibiotic combinations. However, there are frequent clinical situations where this drug must be used in combination with vancomycin to cover Staphylococci and Enterococci, and/or with an imidazole derivative to cover anaerobic species. Similarly, when the pathogens are known to be multiresistant the ceftazidime-aminoglycoside combination has a synergistic bactericidal activity and prevents the emergence of resistant strains. This combination is also recommended in cases where the site of infection is difficult to reach or in immunocompromised patients.

[Efficacy and tolerability of cefixime in lower respiratory tract infections in adults. French multicentric study]. / Efficacité et tolérance du céfixime dans les infections respiratoires basses de l'adulte. Etude multicentrique française.

Cefixime is a new oral cephalosporin with the same activity as that of third generation cephalosporins, particularly against organisms responsible for lower respiratory tract infections. The effectiveness and safety of cefixime were evaluated in the multicentre study reported here. Cure was obtained in 54 of 61 assessable patients suffering from bronchopneumonia (40/44), acute bronchitis (3/5) or acute exacerbations of chronic bronchitis (11/12). The causative agents were eradicated in 35 of 41 assessable cases. No clinical side-effect was observed. Thrombocytosis without clinical manifestations was reported in 14 cases. Administered in doses of 200 mg twice daily, cefixime proved effective and safe in the treatment of lower respiratory tract infections.

[Efficacy and tolerability of cefixime in urinary tract infections in adults. A French multicentric study]. / Efficacité et tolérance du céfixime dans les infections urinaires de l'adulte. Etude multicentrique française.

Cefixime is a new oral antibiotic with in vitro activity similar to that of parenteral third generation cephalosporins. It exhibits good in vitro activity against most pathogens causing urinary tract infections. The effectiveness and safety of cefixime were evaluated in a multicentre study involving 68 patients (45 with acute pyelonephritis, 15 with lower urinary tract infections and 8 with infections of undetermined location); 55 of these patients were assessable in terms of effectiveness. Clinical cure was achieved in 50 cases. The causative agent was always eradicated. During the 3 to 8 weeks' follow-up period, relapses occurred in 5 patients with pyelonephritis. Adverse effects were reported by 2 patients. Biological manifestations (thrombocytosis, elevated ASAT and ALAT) were noted in 5 cases. Cefixime is a safe and effective antibiotic for the treatment of urinary tract infections.

[Current therapeutic indications of aminoglycosides]. / Indications thérapeutiques actuelles des aminoglycosides.

Aminoglycosides still play a major role int e treatment of severe infections, especially those due to Gram-negative bacilli. They are usually administered together with a beta-lactam antibiotic, either to cover a wide antibacterial spectrum, or to obtain a better bactericidal effect, or to prevent the emergence of resistant mutants. They are mainly used in severe urinary tract infections and/or in those due to multiresistant organisms and in Gram-negative pneumonia and meningitis (intrathecally, since they poorly diffuse into the CSF). Combined with cephalosporins they constitute the first-line treatment of severe, life-threatening infections caused by Gram-negative aerobes. Given simultaneously with penicillinase-resistant semi-synthetic penicillins or with vancomycin they act synergistically against staphylococci and can be used initially for a few days in the treatment of severe staphylococcal infections. It is also for this synergistic action that they are combined with penicillin G or ampicillin in the treatment of endocarditis. The ototoxic or nephrotoxic effects common to all aminoglycosides can be avoided by adjusting the doses to the degree of renal function, by limiting their use to about a fortnight (except for endocarditis) and by monitoring blood levels.