[Evaluation of prescription of antibiotics in an intensive care unit]. / Evaluation de la prescription antibiotique dans un service de réanimation polyvalente.

OBJECTIVES: In order to optimize prescriptions, we conducted a qualitative evaluation of antibiotic prescription in an intensive care unit. METHODS: A prospective observational study was performed on 100 consecutive prescriptions from 11/95 to 4/96. RESULTS: Among 14 documented cases, initial antibiotic therapy was in accordance with antimicrobial susceptibility patterns in all but one case. Among 86 empirical cases, 38 were secondarily documented, yielding 43 microorganisms. Of these 38, 27 were susceptible to 2 or more empirical antibiotics, 3 to only 1 and 8 to none. Antibiotics were modified in 23/38 (60%) cases, resulting in drug changes (n = 21) or drug addition (n = 2). In all cases, the new prescription was consistent with the antibiogram. In the 48 cases where no microorganism was isolated, antibiotic change was guided by clinical course and occurred in 6 (12.5%) cases. A switch to older, cheaper or more narrow spectrum antibiotics was possible in 18 cases, but was actually done in only 4 (22%). Dosage errors were observed in 5 cases of initial therapy. Second line therapy contained 8(21%) dosage errors. Most frequently, isolated organisms at admission were: Staphylococcus sp. (n = 15), P. aeruginosa (n = 11) and S. pneumoniae (n = 10). New pathogens emerged in 16 patients (16%) receiving antibiotics. The most frequent was P. aeruginosa in 4 patients receiving ofloxacin + amoxicillin +/- clavulanic acid. CONCLUSION: These results are encouraging, however, the use of guidelines and periodic evaluation of antibiotic prescription practices might improve the efficiency of empirical antibiotic prescriptions and reduce overall antibiotic costs.

[Cerebral toxoplasmosis in HIV infected patients intolerant of cotrimoxazole]. / Toxoplasmose cérébrale chez les patients infectés par le VIH intolérants au cotrimoxazole.

Using results of a multicentric randomized prospective trial of primary prophylaxis of Pneumocystis carinii pneumonia in HIV-infected patients which compared sulfamethoxazole-trimethoprim and pentamidine isethionate, the risk to develop cerebral toxoplasmosis was analyzed in the two assigned groups and in the groups of patients who stopped sulfamethoxazole-trimethoprim prophylaxis. The risk to develop cerebral toxoplasmosis appeared significantly higher in the group of patients who stopped sulfamethoxazole-trimethoprim consecutively to cutaneous hypersensitivity.

Comparison of combination therapy regimens for treatment of human immunodeficiency virus-infected patients with disseminated bacteremia due to Mycobacterium avium. ANRS Trial 033 Curavium Group. Agence Nationale de Recherche sur le Sida.

We conducted a randomized, open-label trial in 42 French hospitals to compare the clinical and bacteriologic efficacy of combination therapy with clarithromycin/clofazimine (Clm/Clof) with that of combination therapy with clarithromycin/rifabutin/ethambutol (Clm/Rib/Eth) as treatment for Mycobacterium avium bacteremia. One hundred forty-four human immunodeficiency virus-seropositive patients older than 18 years of age who had CD4 lymphocyte counts of <100/mm3 and a blood culture positive for M. avium were enrolled in the study. The main measures of outcome were blood cultures, abatement of clinical symptoms (fever), and survival. Treatment success (defined as patient living, either no fever or a reduction of > or = 1 degrees C in initial body temperature, and a blood culture negative for M. avium) was similar in both treatment groups at months 2 and 6. However, following initial resolution of infection, relapse of M. avium bacteremia occurred in more patients in the Clm/Clof group than in the Clm/Rib/Eth group (22 vs. six, respectively; P < .001); these relapses were accompanied by emergence of strains resistant to clarithromycin in 21 and two patients, respectively. In conclusion, combination therapy with Clm/Rib/Eth prevented relapse of mycobacterial disease and, compared with combination therapy with Clm/Clof, was associated with a significant decrease in the emergence of resistant M. avium strains in HIV-infected patients treated for at least 28 weeks.

Incidence and prognosis of embolic events and metastatic infections in infective endocarditis.

AIMS: In infective endocarditis, the true incidence of embolic events and metastatic infections remains unknown probably because a large number of events are asymptomatic. The consequences of the prognosis of such events have never been evaluated by a prospective follow-up. This study aimed to assess the incidence of symptomatic or asymptomatic embolic events and metastatic infections in definite infective endocarditis and to determine whether these events carry a risk of mortality. METHODS AND RESULTS: From January 1991 to December 1993, 102 patients with suspected or known infective endocarditis were referred to our institution. Among them, we selected 68 patients (50 males, 18 females, mean age = 52.7 years) exhibiting definite infective endocarditis according to the Duke University criteria. Blood cultures were positive in 49 cases (72%). Echocardiography revealed valvular vegetations in 55 cases (81%). Irrespective of the clinical presentation, patients were examined radiologically by cerebral computed tomography scanning (n = 60), magnetic resonance imaging (n = 3), abdominal computed tomography scanning (n = 32) or abdominal echocardiography (n = 20). Depending on the symptoms, thoracic computed tomography scanning (n = 22), pulmonary angiography (n = 2), ventilation-perfusion scintigraphy (n = 4), or gallium citrate radionuclide scanning (n = 7) were also performed. All patients were prospectively followed-up for a mean period of 21.4 +/- 17.5 months. In 35 patients (51%), 51 embolic or metastatic events were revealed, involving the central nervous system (n = 23), spleen (n = 7), kidney (n = 5), lung (n = 5), liver (n = 4), bone and joint (n = 4), iliac (n = 2) or mesenteric (n = 1) arteries. During the hospital stay, the mortality rate was higher in patients exhibiting embolic or metastatic events (20 vs 12%), but the difference did not reach statistical significance. Kaplan-Meier analysis demonstrated no difference in long-term follow-up. CONCLUSION: Our data suggest that embolic or metastatic events had a high incidence (51%) during infective endocarditis, but were not associated with significant attributable mortality.

Severe community-acquired pneumonia in ICUs: prospective validation of a prognostic score.

OBJECTIVE: To determine predictors of intensive care unit (ICU) mortality in patients with community-acquired pneumonia (CAP), to develop a pneumonia-specific prognostic index, and to evaluate this index prospectively. DESIGN: Combined retrospective and prospective clinical study over two periods: January 1987-December 1992 and January 1993-December 1994. SETTING: Four medical ICUs in the north of France. PATIENTS: Derivation cohort: 335 patients admitted to one ICU were retrospectively studied to determine prognosis factors and to develop a pneumonia-specific prognostic index. Validation cohort: 125 consecutive patients, admitted to four ICUs, were prospectively enrolled to evaluate this index. RESULTS: In the derivation cohort, 16 predictors of mortality were identified and assigned a value directly proportional to their magnitude in the mortality model: aspiration pneumonia (-0.37), grading of sepsis > or = 11 (-0.2), antimicrobial combination (-0.01), Glasgow score > 12+mechanical ventilation (MV) (+0.09), serum creatinine > or = 15 mg/l (+0.22), chest involvement shown by X-ray > or = 3 lobes (+0.28), shock (+0.29), bacteremia (+0.29), initial MV (+0.29), underlying ultimately or rapidly fatal illness (+0.31), Simplified Acute Physiology Score > or = 12 (+0.49), neutrophil count < or = 3500/ mm3 (+0.52), acute organ system failure score > or = 2 (+0.64), delayed MV (+0.67), immunosuppression (+1.38), and ineffective initial antimicrobial therapy (+1.5). An index was obtained by adding each patient's points. According to a receiver operating characteristic curve, the cut-off value of this index was 2.5. In the validation cohort, an index of > or = 2.5 could predict death with a positive predictive value of 0.92, sensitivity 0.61, and specificity 0.98. CONCLUSION: This index, which performs well in classifying patients at high-risk of death, may help physicians in initial patient care (appropriateness of the initial antimicrobial therapy) and guide future clinical research (analysis and design of therapeutic trials).

Fatal infection of coronary stent implantation.

Among systemic infections occurring after percutaneous transluminal coronary angioplasty (PTCA) and coronary stent implantation, septic cardiac complications are rare. We report a new case of infective aneurysm of the left anterior descending coronary artery (LAD) following stent implantation. Infective mitral endocarditis due to Pseudomonas aeruginosa occurring a few weeks after stenting led to search for stent infection. Coronary angiography revealed a saccular aneurysm of the LAD. Despite surgical repair, a fatal outcome resulted.

[Urinary infections in pregnant women]. / L'infection urinaire chez la femme enceinte.

Urinary tract infection is frequent during pregnancy with a high potential risk for mother and child. Based on a review of the literature and a retrospective survey conducted in 20 representative French university hospitals during 1993, the authors propose a practical review designed to standardize the therapeutic approach to this disease. They define a high-risk group which requires systematic screening and close surveillance during pregnancy. They evaluate the need for complementary investigations in relation to the 3 clinical presentations encountered (asymptomatic bacteriuria, cystitis and acute pyelonephritis) taking into account their respective adverse effects. The therapeutic modalities of the three clinical forms are then described, including drainage of the urinary tract.

Reliability of quantitative cultures of protected specimen brush after freezing.

Protected specimen brush (PSB) is considered to be one of the standard methods for diagnosing mechanical ventilator-acquired pneumonia at a threshold value > or = 10(3) cfu/ml. Nevertheless, this procedure requires immediate cultures which are not always possible 24 h per day. We therefore wanted to appreciate the diagnostic value of delayed quantitative cultures after specimen freezing. PSB was performed by fiberoptic bronchoscopy on 43 mechanically ventilated patients with suspicion of nosocomial bronchopneumonia. After PSB procedure, two aliquots of 0.5 ml were prepared. One aliquot was plated immediately on different culture media (Group 1). A second aliquot was frozen at -80 degrees C for 24 h, then plated on the same culture media as Group 1 (Group 2). All samples were incubated for 48 h. The diagnostic value threshold of PSB was 10(3) cfu/ml. A total of 47 samples were performed on 43 patients. In Group 1, cultures from PSB were positive in 26 samples and revealed 41 species yielding > or = 10(3) cfu/ml. In Group 2, PSB cultures were positive in 24 samples and revealed 36 species yielding > or = 10(3) cfu/ml. Despite a mean decrease in bacterial count of 1.00 +/- 1.44 log 10 (p < 0.001), most important for Streptococcus pneumoniae and Escherichia coli (respectively 3.22 +/- 2.21 log10 and 2.41 +/- 0.52 log 10), sensitivity and specificity of quantitative cultures after specimen freezing, compared with immediate cultures, were 88% and 100% respectively. We concluded that specimens from PSB could be frozen at -80 degrees C with good reliability except for S. pneumoniae and E. coli, enabling PSB procedure to be performed around the clock.

Empirical monotherapy with meropenem in serious bacterial infections. Meropenem Study Group.

A multicentre, open, randomised, parallel group study was carried out to assess the efficacy and safety of meropenem monotherapy versus the combination of ceftazidime plus amikacin in the treatment of serious bacterial infections. Adult, hospitalised patients (n = 237) were included if they had infections at one or more of the following sites: lower respiratory tract (89 community-acquired; 84 hospital-acquired), urinary tract (59 complicated; 3 uncomplicated), skin and skin structures (n = 8), or septicaemia (n = 29). Patients were randomised to receive either iv meropenem (1 g every 8 h) as monotherapy or iv ceftazidime (2 g every 8 h) plus iv amikacin (15 mg/kg/day in two or three divided doses). Meropenem had comparable clinical efficacy to ceftazidime plus amikacin in: community-acquired lower respiratory tract infection (LRTI) (40/43, 93% vs 31/39, 79% cured or improved); hospital-acquired LRTI (30/37, 81% vs 23/32, 72%); septicaemia (10/12, 83% vs 16/17, 94%) and complicated urinary tract infection (UTI) (13/15, 87% vs 25/25, 100%). A similar proportion of patients in each treatment group experienced adverse events, the most frequent being transient elevations in serum transaminases. Seven patients in the meropenem group and eight patients in the ceftazidime plus amikacin group died during the study period from reasons unrelated to study medication, and seven patients (five meropenem, two ceftazidime plus amikacin) were withdrawn due to adverse events. Empirical monotherapy with meropenem is as well tolerated and as effective as the combination of ceftazidime plus amikacin in the treatment of serious infections.

A five-year study of severe community-acquired pneumonia with emphasis on prognosis in patients admitted to an intensive care unit.

OBJECTIVES: To characterize the epidemiology and to determine the prognosis factors in severe community-acquired pneumonia among patients admitted to an intensive care unit. DESIGN: Retrospective clinical study. SETTING: Intensive Care and Infectious Diseases Unit of a municipal general hospital of Lille University Medical School. PATIENTS: 299 consecutive patients exhibiting severe community-acquired pneumonia. MEASUREMENTS AND RESULTS: On admission to ICU, 149 patients required mechanical ventilation for acute respiratory failure and 44 exhibited septic shock. Pulmonary involvement was bilateral in 71 patients. There were 260 organisms isolated from 197 patients (65.9%), the most frequent being Streptococcus pneumoniae (n = 80), Staphylococcus spp. (n = 57) and Gram-negative bacilli (n = 81). Overall mortality was 28.5% (85 patients). According to univariate analysis, mortality was associated with age over 60 years, anticipated death within 5 years, immunosuppression, shock, mechanical ventilation, bilateral pulmonary involvement, bacteremia, neutrophil count < 3500/mm3, total serum protein level < 45 g/l, serum creatinine > 15 mg/l, non-aspiration pneumonia, ineffective initial therapy and complications. Multivariate analysis selected only 5 factors significantly associated with prognosis: anticipated death within 5 years, shock, bacteremia, non-pneumonia-related complications and ineffective initial therapy. CONCLUSION: The effectiveness of the initial therapy appears to be the most significant prognosis factor and, as the one and only related to the initial medical intervention, suggests a need for permanent optimization of our antimicrobial strategies.

Amikacin levels in bronchial secretions of 10 pneumonia patients with respiratory support treated once daily versus twice daily.

In this study, concentrations of amikacin in blood and bronchial secretions of 10 patients with mechanical ventilation for acute respiratory failure due to pneumonia were measured. One-half of the patients received amikacin twice daily, and the others received once-daily administration. Concentrations in bronchial secretions of the patients treated twice daily ranged from 3 to 4 mg/liter, i.e., they were similar to those in previously published reports. Peak concentrations in bronchial secretions occurred between 3 and 4 h after the onset of infusion, and they reached 4.8 +/- 2.6 mg/liter on day 1 and 4.0 +/- 2.7 mg/liter on day 3. For the patients treated with amikacin once daily, concentrations in bronchial secretions were more than twofold higher, above 8 mg/liter for 12 h. Peak concentrations in bronchial secretions occurred between 3 and 4 h after the onset of infusion and reached 13.6 +/- 9.3 mg/liter on day 1 and 10.4 +/- 3.5 mg/liter on day 3. These concentrations are higher than the MICs for less sensitive bacterial strains, such as Acinetobacter spp. and Pseudomonas aeruginosa.

Trimethoprim-sulfamethoxazole versus aerosolized pentamidine for primary prophylaxis of Pneumocystis carinii pneumonia: a prospective, randomized, controlled clinical trial. LFPMI Study Group. Ligue Française de Prévention des Maladies Infectieuses.

The objective was to compare the efficacy and tolerance of monthly aerosolized pentamidine versus trimethoprim-sulfamethoxazole (TMP-SMX) to prevent the first episode of Pneumocystis carinii pneumonia (PCP) in human immunodeficiency virus (HIV)-infected patients. In an open, prospective, randomized multicentric clinical trial, HIV-infected patients (n = 214) with CD4 cell counts < 200/mm3 or 20% without a history of PCP or cerebral toxoplasmosis were randomized to receive for at least 2 years aerosolized pentamidine (300 mg monthly) or low-dose daily TMP-SMX (400-80 mg). The mean follow-up was 578 days. The two groups (except for gender) were homogeneous for age, risk group for HIV infection, initial CD4+ lymphocyte count, and mean follow-up. The PCP rate per year of observation using an intent-to-treat analysis was 3.1% and 1.3% in the groups treated with pentamidine and TMP-SMX, respectively (p > 0.05). Moderate or severe clinical and biological side effects were observed in five patients on pentamidine and 33 on TMP-SMX (p < 0.05). Nineteen episodes of cerebral toxoplasmosis were diagnosed during the study. The analysis showed no significant difference in time of development of toxoplasmosis, but only one patient was actually treated with TMP-SMX. Survival was not significantly different in the two groups. Low-dose daily TMP-SMX or monthly aerosolized pentamidine effectively prevented a first episode of PCP in HIV-infected patients, but aerosolized pentamidine was better tolerated. However, TMP-SMX is less costly and should have a preventive effect for toxoplasmosis.

[Coronary-left ventricular fistula in post-infarction of the myocardium. Apropos of a new case. Review of the literature]. / Fistule coronaro-ventriculaire gauche post-infarctus du myocarde. A propos d'un nouveau cas. Revue de la littérature.

The authors report a new case of acquired corono-left ventricular fistula found in a 46-year-old man four months after a first myocardial infarction treated by fibrinolysis then conventional angioplasty. This is one of the rare cases of post-infarction corono-ventricular fistula, only five of which have been reported in the literature. While their described features seem relatively constant, enabling their distinction from post-angioplasty corono-ventricular fistulas (also rarely described: four cases), certain doubts persist as to their treatment, and above all their mechanism. Monitoring for four years by coronary angiography, which is the special feature of the case reported here, leads us to include this entity within the wider context of post-infarction ventricular remodelling, of which it would then be a very rare complication.

[Severe infections caused by methicillin-resistant Staphylococcus aureus. 62 cases]. / Infections graves à staphylocoques dorés résistants à la méticilline. 62 observations. GEISS. Groupe d'étude des infections sévères à staphylocoques.

A French multicentre study was conducted in 15 Infectious Diseases departments; 347 cases of severe staphylococcal infections were collected during one year (October 1989 to October 1990): Two-hundred and fifty-eight strains were analysed with complementary bacteriological studies, including 62 strains of methicillin-resistant Staphylococcus aureus. Epidemiological, clinical and therapeutic aspects were investigated. Nosocomial infection was responsible for 90 percent of the cases, and previous antibiotic therapy was reported in 74 percent. An invasive procedure was incriminated in 43 patients (69 percent); intravenous catheter (38 percent), mechanical ventilation (31 percent), surgery (22 percent), prosthetic device (20 percent). Thirty-nine patients were treated with glycopeptides either alone or in combination with beta-lactams, aminoglycosides, fucidic acid, fosfomycin, rifampicin, quinolones or synergistines, showing the great diversity in the choice of antibiotics in methicillin-resistant S. aureus infections. More than 90 percent of these strains were resistant to gentamicin and quinolones, 80 percent of clindamycin and 70 percent to rifampicin. No resistance to glycopeptides (vancomycin or teicoplanin) was observed. Prognosis was severe, with a mortality rate of 35 percent, justifying educational and prophylactic measures in at risk medical departments.

Pharmacokinetics of vancomycin during continuous hemodiafiltration.

OBJECTIVE: To study the pharmacokinetics of vancomycin in three patients with acute renal failure related to multi-organ failure during continuous venovenous hemodiafiltration (CVVHD). DESIGN: Prospective exploratory, open-labelled study. SETTING: Critical Care Unit in a University Medical Centre. PATIENTS: 3 patients exhibiting hemodynamic instability and oligo-anuric acute renal failure requiring extra-renal epuration were included in this study. INTERVENTION: Every patient received 7.5 mg/kg IV vancomycin over 1 h for a documented or suspected nosocomial staphylococcal infection. Serum and dialysate outlets samples were collected before infusion and 1, 3, 6, 12, 18, 24 after the end of infusion. MEASUREMENTS AND RESULTS: Mean age was 58.7 years (range 41-79) and mean SAPS 15.7 (9-23). The mean peak concentrations were 27.3 mg/l (range 15.6-45.6) one hour after the end of infusion. The average remaining vancomycin concentration 24 h after the onset of infusion was 3.6 mg/l (range 2.6-4.5). The mean terminal disposition rate constant and elimination half-life were 0.05 h-1 and 13.9 h respectively. Mean total body clearance was 38.9 +/- 4.3 ml/min and dialysate outlet (DO) clearance 4.2 +/- 1.3 ml/min. The mean volume of distribution was 47.4 +/- 6.4 l. CONCLUSION: CVVHD is effective for vancomycin elimination. In these patients, the elimination half-life is almost constant, involving a following injection of vancomycin 12 h later to achieve effective concentrations.