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Background: Endogenous endophthalmitis is a devastating infection of the eye that leads to blindness in about two-thirds of patients. It results from the haematogenous spread of a microorganism from a focus of sepsis, mainly gastro-intestinal, genitourinary or cardiac., Patients and Methods: We describe the case of a diabetic subject presenting endogenous endophthalmitis following erysipelas of the leg due to Streptococcus agalactiae. The outcome was favourable thanks to prompt initiation of appropriate antibiotic treatment., Discussion: Endogenous endophthalmitis as a complication of a skin infection is a rare entity, with only about 30 reported cases in the literature. Awareness of this condition among dermatologists would allow prompt intervention, which is essential for sparing of the patient's eyesight., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)

We studied the production of metallo-β-lactamases (MBL) in Acinetobacter baumannii and Pseudomonas aeruginosa strains resistant to imipenem at the Rabat Mohammed V military teaching hospital, according to Yong et al.'s method, using a sterilized solution of EDTA 0.5 M pH 8. One hundred and five bacterial strains (48 A. baumannii and 57 P. aeruginosa) were identified. 45 (42.9%) with 34 A. baumannii and 11 P. aeruginosa were resistant to imipenem. The prevalence of MBL producing strains was 22.2% (10/45). The existence of this isolates resistant to imipenem by producing metallo-β-lactamases is an emerging public health problem. It is necessary to implemente infection control programs to avoid spreading of multidrug resistant bacteria.

We have collected cases of iatrogenic meningitis managed in the Children's Hospital of Tunis, between January 1998 and December 2006. Clinical information about each patient were collected, all bacterial samples were investigated in the microbiology laboratory of the hospital. Bacterial isolates were identified according to conventional criteria. In the interval under study, we recorded three cases of iatrogenic meningitis after lumbar puncture. Two cases occurred in newborn admitted for suspicion of neonatal infection and one in a 2-month-old infant admitted for exploration of hyperpyretic convulsion. In all patients, the initial cerebrospinal fluid was normal. All patients developed symptoms of acute meningitis within 72 hours after lumbar puncture; the second cerebrospinal fluid was, then, typical for purulent meningitis. The causal agents isolated in the three cases were Klebsiella pneumoniae, Enterobacter cloacae, and Serratia marcescens, all resistant to beta-lactams by extended spectrum beta-lactamase production. The use of quinolones was required in all cases. Different complications were recorded: hydrocephalus and brain abscess in one case, respiratory and hemodynamic failure managed in the intensive care unit in the second, and brain hygroma in the third case. This study shows high morbidity of iatrogenic meningitis. Simple aseptic precautions undertaken before the procedure of lumbar puncture can prevent such cases. The urgent need for increasing the awareness among medical personnel in hospitals of developing countries cannot be overemphasized.

Aim of the Study: The antibiotic resistance of enterobacteriacae knows a worldwide worrying evolution with an increase of the extended spectrum betalactamases (ESBL) that spread into the community. Few publications describe this problem in the Indian Ocean area. The aim of this study is first to identify in Félix Guyon Hospital (Reunion Island) the emergent antibiotics resistance for enterobacteriaceae between 1997/1998 and 2006/2007 periods, at second, to update the prophylactic and therapeutic measures for handling the risk linked to multiresistant enterobacteriaceae in our hospital and third, to assess the risk in Reunion Island and especially at the community level., Methods: The antibiotic susceptibility of 7814 enterobacteriaceae strains collected among patients, during 1997/1998 and 2006/2007 periods, were analysed as well as the consumption of the third generation cephalosporins, imipenem and fluoroquinolones., Results: Within a span of time of 10 years, an important increase (+57 %) of the resistance prevalence of enterobacteriaceae is observed. The resistance by the ESBL production mechanism is predominant especially for Enterobacter cloacae and Escherichia coli. An important use of broad spectrum antibiotics is correlated with this resistance evolution., Conclusion: The emergence of ESBL-producing enterobacteriaceae in our hospital is impairing both therapeutic and health care. It requires a much better control of antibiotics prescriptions and therefore, an important multidisciplinary implication. A proof molecular analysis would allow to evaluate the risk more precisely, especially at the community level., (Copyright (c) 2009 Elsevier Masson SAS. All rights reserved.)

CSF sterilization should be obtained very rapidly to reduce both mortality and morbidity due to bacterial meningitis. Thus, antibiotic treatment should be adapted to the suspected bacterium and administered as early as possible at high dosage with - if necessary - a loading dose and continuous perfusion. The rates of abnormal susceptibility to penicillin of Streptococcus pneumoniae, Neisseria meningitis and Haemophilus influenzae are 37%, 30% and 12% respectively. Thus, ceftriaxone or cefotaxim must be used as empirical treatment. Listeria monocytogenes remains fully susceptible to aminopenicillin, so, the combination aminopenicillin and aminoglycoside is the first-line treatment. Antibiotic resistance, allergy or contra-indications, are in fact rare but in these cases, antibiotic combinations are often needed. The latter are more or less complex and clinically validated; they include molecules such as vancomycine, fosfomycin, fluoroquinolone or linezolid.

Introduction: Cutaneous infections due to Mycobacterium fortuitum, a rapidly growing environmental mycobacteria, are often iatrogenic, resulting from surgery or injection. We report two cases following plastic surgery and describe the outcome after surgery and antibiotics., Case Reports: Two immunocompetent women underwent abdominal plastic surgery and liposuction, which were complicated with recurrent abscesses one and 13 months later respectively. Cultures of bacteriologic samples isolated M. fortuitum in the two patients. The two strains exhibited different antibiotic sensibility profiles. The initial antibiotic therapy consisted of combined amikacin and moxifloxacin in both patients plus imipenem in one, followed by oral doxycycline and clarithromycin in one and moxifloxacin in the other for a total duration of nine and five months, respectively. In both cases, surgical treatment was also given before, during and after antibiotic therapy. No new lesions had appeared six months after the end of antibiotic therapy., Discussion: Cutaneous infections due to M. fortuitum are rare and secondary to iatrogenic skin wounds. The clinical appearance is not specific, accounting for delayed diagnosis. Treatment is difficult and there is no consensus. According to our experience, surgical treatment is essential whereas the efficacy of antibiotics, even involving multiple agents, seems more doubtful.

Objective: to characterize epidemiological and clinical features related to the multi-drug Acinetobacter baumannii infections in the university hospital Sahloul in Tunisia., Material and Methods: retrospective study including twenty-four imipenem resistant Acinetobacter baumannii isolated from twenty patients hospitalized in different wards of the hospital. Study of clinical features related to the infection by multi-drug Acinetobacter baumannii, bacterial identification by classical identification scheme, antibiotic susceptibilities were determined by the disk diffusion method; genotyping was performed by arbitrarily-primed PCR., Results: the most incriminated ward was the intensive care unit with a high prevalence of septicaemia. All studied strains were multi-drug to all beta-lactams tested. Genotyping has shown the clonality of studied strains. Features incriminated in the acquisition of infection were essentially immunodeficiency, invasive manoeuvring and antibiotherapy., Conclusion: multidrug Acinetobacter baumannii is increasingly isolated in our hospital. Rational use of antibiotics and rigorous application of hygienic rules could contribute to limit dissemination of such strains.

This retrospective study analyses an epidemic with germs ESBL that supervenes at the department of hematology and pediatric oncology in UHC Ibn Rochd of Casablanca. The responsible germ is the ESBL Escherichia coli. Six patients have been infected during the same period that 2 are female and 4 are male. Five patients had acute lenkemia, one patient had a non Hodgkin's disease. All the patients were in the stage of a deep postchermotherapy neutropenia. The picture of all the patients represented a severe infection with suffered fever and acute diarrhea. Five patients died with apicture of septic shock in the 48 to 72 hours after the beginning of the infection and before the identification of the germ. Their treatment consisted in the third generation of cephalosporin and aminoside. One patient who use the imipeneme more the aminoside has been apyrexized the epidemic and severe situation led to the closing of the unit during a week in order to do a disinfection. After 12 monthes of recession, few isolate episodes of infections with enterobacteries ESBL have observed and controlled. The factors that determine the increase and the diffusion of the ESBL germ are numerous and some of them are still not identified, the means of prevention consisted in: the fight against the selection of the resistant germs, the fight against the colonization of the patients by these germs and their transmission between the patients, this requires measures of hygiene and particularly the washing of the hands.

Introduction: Infection with Streptobacillus moniliformis is an uncommon illness which can lead to death if untreated. We report the case in which initially cutaneous signs permitted diagnosis and further identification of the organism., Case Report: A 42 year-old woman presented with a three-day history of acrally distributed purpuric macules on her fingers. Two days later, she was admitted for arthritis of the knees and wrists. There were two large pustules on the left elbow and the right knee. Laboratory studies showed inflammatory changes. The diagnosis of streptobacillary rat-bite fever was made after isolation of Gram-negative bacilli from a blood-culture and from cutaneous lesions. Finally identification of the organism was made by molecular biology analysis. The patient received intravenous ofloxacin and imipenem with complete resolution of arthritis and the cutaneous lesions., Discussion: Streptobacillary rat-bite fever is a systemic infectious disease. It is caused by Streptobacillus moniliformis, organism found in the oropharyngeal flora of small rodents, especially rats. The illness is uncommon in urban settings. It starts by fever, followed by arthritis and rash. Septicaemical rat-bite fever may start only with cutaneous involvement such as acral purpura, like in our case. This clinical manifestation must be recognized by the dermatologist, because the illness can lead to death if untreated.

Introduction: Bacterial intracerebral aneurysms, which are a common complication of infectious endocarditis, are unusual without Osler's disease., Exegesis: From the case report of a man with a bilateral bacterial intracranial aneurysm without endocarditis resulting in an hypopituitarism, we undertook a literature review of bacterial intracerebral aneurysms without endocarditis., Conclusion: Although this review has found few cases, this kind of aneurysms seems to have different features from those secondary to infective endocarditis: younger age of incidence, majority of Staphylococcus aureus, clinical presentation as a thrombophlebitis of the cavernous sinus, location of aneurysm on bigger cerebral artery.

We describe a case of penetrating spinal cord injuries in an 20-year-old man after stab wound attack. The outcome was complicated with subarachnoid fistula and meningitis. The diagnosis and management of these complications are discussed.

Background: During the course of acute hepatitis B, hematology disorders are common though they are generally mild and occur early. Agranulocytosis is exceptional and occurs late in the disease course., Case Report: We report a case of agranulocytosis which developed 3 weeks after onset of acute hepatitis B in an HIV-positive patient. Peripheral and central hematological disorders led to the diagnosis. Agranulocytosis developed during the cytolytic phase of the primary hepatitis B infection and regressed after administration of hematopoietic growth factors., Discussion: It is sometimes difficult to establish the causal effect of hepatitis B in the development of agranulocytosis in patients with an HIV co-infection who are on a multiple drug regimen and subject to multiple bacterial, viral or parasite infections.

Mice experimentally infected with extended-spectrum beta-lactamase-producing Klebsiella pneumoniae strains were injected twice daily for three days with ceftazidime, cefepime, or imipenem (25, 50, or 100 mg/kg/injection). Treatment efficacy was based on five-day survival and on the spleen viable bacteria count 16 hours after the last treatment dose. Under these experimental conditions, ceftazidime showed some activity on strains with low levels of resistance to ceftazidime. Cefepime used in a dose of 50 or 100 mg per injection demonstrated good activity but was slightly less effective than imipenem.

Do immunocompromised children, carrying vancomycin-resistant enterococci (VRE) need to be treated? For 3 years, 230 children with chemotherapy and/or bone-marrow transplantation (BMT) received amikacin for gut decontamination and rinsed their mouth with solutions including vancomycin or not, according to the duration and severity of neutropenia. Some patients were isolated, others were at home with ambulatory treatment. The first-line antibio-therapy was piperacillin-amikacin-vancomycin in the chemotherapy unit, imipenem-vancomycin in the BMT unit. Once-a-week, the laboratory used to check the efficiency of decontamination procedures and look for emerging resistant bacteria. Four patients were identified as VRE carriers in their gut flora. The fecal carriage was long-lasting in a single patient, for whom attempts of eradication failed. No patient underwent VRE bacteremia. From our experience, it seems reasonable to neglect enterococcal eradication, provided that hygienic measures are strictly applied.

Carbapenems such as imipenem are beta-lactam antibiotics usually stable to the hydrolytic activity of beta-lactamases. Nevertheless, resistance to imipenem by production of carbapenemases has been described in few species of Gram negative bacilli. This mechanism of resistance remains exceptional in Enterobacteriaceae. These carbapenemases are principally metallo-enzymes that possess a zinc ion in their active site. Enterobacter cloacae strain NOR-1, is resistant to imipenem by production of an inducible chromosomal beta-lactamase which is not a metallo-enzyme but an Ambler class A beta-lactamase. This enzyme displays a strong hydrolytic activity against carbapenems but also against cephamycins which has never been previously observed for beta-lactamases of this class. These properties suggest that NMC-A possesses an original tridimensional structure of its active site allowing hydrolysis of molecules generally protected by the configuration of their lateral chain. Crystallographic study of this enzyme will permit to understand its mechanism of action and serve the development of new beta-lactams stable to b-lactamase hydrolytic activity.

Monotherapy with ceftazidime, cefepime, imipenem or meropenem for the empiric treatment of febrile neutropenia appears as effective as the combination therapy involving aminoglycosides. However, empiric therapy with a combination of a beta-lactam plus an aminoglycoside is a reasonable decision under circumstances where Gram negative sepsis is very likely. Monotherapy is usually associated with a modest rate of response in infections caused by Gram positive organisms. In about 30% of the patients, a glycopeptide will be added at some point, because the response to the initial therapy is not considered optimal.

Primary peritonitis caused by Streptococcus pneumoniae is a rare but serious complication of childbirth. We present here three cases of young women who developed abdominal pain after childbirth. All of the patients had fever with abdominal pain, diarrhea and clinical signs of peritonitis. In two cases a laparotomy was performed to remove pus. Cultures taken were positive for Streptococcus pneumoniae. Culture of vaginal swabs and blood cultures were also positive for the same pathogen. For the third patient, both vaginal swabs and blood cultures were positive for Streptococcus pneumoniae, antibiotic therapy only was administered. Outcome was favorable for all. We discuss the pathogenesis, clinical presentation, management and the usefulness for systematic search "for" Streptococcus pneumoniae in vaginal swabs.

Imipeneme, a molecule chemically related to the carbapenems (beta-lactam), is a potent wide spectrum antibiotic reserved for hospital use. Effective as therapy for major infections, and for use in severely debilitated patients (immunodepressed, etc ...) its efficacy in the treatment of peritonitis has been demonstrated in numerous studies abroad, confirmed by results of a French multicenter trial in 1989. Its cost-effectiveness ratio was assessed as excellent in a comparative case-controlled study of totally matched patients treated with other antibiotics. As expected, the cost of the treatment itself (imipeneme/cilastatine plus associated products and costs of their administration) was higher by about 1000 F per patient when compared with other antibiotic regimens, but its markedly superior efficacy allowed overall economies of about four and a half times this sum (4300 F). This cost reduction was related to different factors, some of which could not be individualized because of missing data (personnel) or protocol bias (laboratory examinations). Nevertheless, the global result was a shortening of hospital stay by more than two days due to a very pronounced decrease in failure rate of the first treatment. This result is even more remarkable in that the peritonitis treated by Tienam was significantly more severe than that treated by the other antibiotics.

Eighty eight patients over the age of 70 years, suffering from peritonitis, were treated with imipenem/cilastatin single-agent therapy as a complement to surgery. The recommended dosage was 30 mg/kg/day and could be increased up to 50 mg/kg/day, without exceeding four grams per day, administered by four infusions per day. Seventy three patients (32 males, 41 females) with a mean, age of eighty years and suffering from peritonitis due to perforation, were evaluated. One half of patients presented one or several risk factors on inclusion into the study, one third received ventilatory assistance and 28.5% presented with shock. The perforation was situated in the stomach and duodenum (N = 24), biliary tract (N = 8), small intestine (N = 3), caecum (N = 10) and colon or sigmoid (N = 28). The infection was polymicrobial in 57.4% of cases. Blood cultures were positive in seven patients and cultures remained sterile in seven patients. A clinical success was obtained in sixty four patients (87%): fifty-six patients were cured and eight were improved. Six patients died as a result of infection (mortality: 8.2%) and three were not improved. No failure was due to development of an imipenem-resistant organism. These results confirm the efficacy of imipenem/cilastatin single-agent therapy as a complement to surgery for severe intra-abdominal infections in this high-risk elderly population.

A three-arm prospective randomized trial was designed to compare the effectiveness of single drug therapy with imipenemcilastatin (IC), two-drug therapy with ceftazidime-vancomycin (CV), and three-drug therapy with ticarcillin-vancomycin-amikacin (TVA) for the empirical antimicrobial treatment of febrile neutropenia events. The objectives of the study were to determine whether IC monotherapy was as effective as combination drug therapy (CV or TVA) and to assess the value of adding vancomycin at initiation of treatment. One hundred eighty-three febrile neutropenia events were randomized and 125 were evaluable. Success rates were 73% with IC, 67% with CV, and 72% with TVA. There were no statistically significant differences between the three treatment groups, regardless of the duration and severity of neutropenia. Fifty-four bacterial isolates were recovered from 43 patients. Among recovered bacterial strains, 55% were Gram-negative and 45% were Gram-positive. Rates of bacteriologically documented failures (14/33) and superinfections (3/33) were similar in the three groups. Adverse events were rare but two patients given CV and three given TVA developed severe skin toxicity requiring modification of the antimicrobial regimen. IC alone showed similar effectiveness and less toxicity, as compared with CV or TVA. Vancomycin given initially increased toxicity but failed to improve the success rate. Vancomycin may be appropriate only in patients at high risk for infection with methicillin-resistant staphylococci.

The antibiotic treatment of peritonitis classically resorts to the association of two and even three molecules. In order to test the efficacy of a single-drug therapy with Tienam* imipenem/cilastatin) as an adjunctive treatment associated to surgery for perforation peritonitis, an open, non-comparative study of 257 patients was carried out in 28 departments. Imipenem is the first beta-lactam antibiotic of the carbapenem family. This antibiotic seems to be particularly useful for the treatment of mixed polymicrobial infections such as peritoneal infections, owing to its activity spectrum covering Gram-positive and Gram-negative, aerobic and anaerobic germs, including strands with multiple resistances (Enterobacter, Pseudomonas aeruginosa, Serratia marcescens, Acinetobacter, Enterococcus and Bacteroides fragilis). A total of 212 patients were assessed with a treatment averaging 7 days. The five most frequently isolated bacteria were Escherichia coli, streptococci, Bacteroides, Proteus and Klebsiella. The healing or improvement rate was 95.3% (202/212). Seven cross-infections occurred during of after the treatment. Tolerance is good in 96% of all cases. Adverse effects were infrequent and mild: the hepatic and hematological alterations never required the interruption of the treatment and they were reversible; the treatment was interrupted in one patient only because of omental tremulation.

A mouse model of experimental Pseudomonas aeruginosa peritonitis was used to evaluate the emergence of resistant mutants during antimicrobial therapy. Mice were infected intraperitoneally with a large inoculum (10(8) CFU + 125 mg talcum) of one of eight strains of Pseudomonas aeruginosa and treated for eight hours with imipenem (IPM) (2 mg/kg/60 min), ciprofloxacin (CIP) (5 mg/kg/45 min), ceftazidime (CAZ) (2 mg/kg/45 min), and amikacin (AN) (2 mg/kg/45 min), alone or in combination. Dosages were selected to achieve and maintain for 8 hours intraperitoneal concentrations similar to those seen in human bronchial secretions. Emergence of resistant strains occurred in 88% of mice after IPM, 29% after CIP, and 31% after CAZ. MICs for resistant strains were increased 8-fold to 512-fold above baseline. Given in combination, IPM and CIP use was followed with lower rates of resistance to each drug (6% and 2% respectively) than use of each antimicrobial alone (p less than 0.001). Combination with amikacin reduced resistance rates for all the antimicrobials studied. No resistant strains occurred with the CIP-CAZ combination. Under the experimental conditions used, the CIP-CAZ combination provided the best results, although the difference with the CIP-IPM combination was not statistically significant.

Despite the therapeutic progress, the possible consequences of salpingitis remains serious: they consist essentially of sterility and ectopic pregnancy. Unfortunately, the biological and etiological diagnosis encounter many difficulties: samples difficult to obtain, slowness of the laboratory. On the basis of the fact that infections of the Fallopians often involve several organisms, the clinician could begin active treatment from the outset versus enterobacteria, anaerobes and Chlamydia. In vitro investigation of imipenem-ofloxacin and imipenem-doxycycline associations versus Chlamydia trachomatis have demonstrated that imipenem has no anti-chlamydia activity. The addition of ofloxacin or oxydoxycycline has no antagonistic effect. These experimental findings justify the clinician's use of an association of imipenem/cilastine for the initial treatment of upper genital tract infection.

The diffusion of imipenem (IMP) in the knee joint was studied after a 1 g i.v. administration of Tienam over one hour. The synovial fluid was collected under anesthesia during arthroscopy carried out for mechanical lesions of the knee (meniscal lesions after ligamental injuries or sequelae after meniscectomy), in 3 groups of six patients at one, two, or three hours after the end of injection of IMP. The concentrations of IMP determined by high performance liquid chromatography (HPLC) were: 42.5, 20.1, 9.3 and 5.7 mg/l in the blood at T0, T1, T2 and T3 hr, respectively; 20.4, 13.0 and 7.9 mg/l in the synovial fluid at T1, T2 and T3, respectively. The decrease of IMP concentrations in the synovial fluid was 1,5 times as low as in serum. On account of its broad-spectrum antibacterial activity and our data, IMP could be used in perioperative prophylaxis of the knee joint surgery.

Nosocomial infections by Pseudomonas aeruginosa seen in a general intensive care unit from January 1987 through December 1989 were studied. Use of piperacillin, ticarcillin, cefsulodine, ceftazidime, and imipenem over the same period were recorded. Rate of infection by P. aeruginosa among the 1,844 patients admitted during the study period was 3.2%; 32% of all nosocomial infections during this period were due to P. aeruginosa. The proportion of P. aeruginosa strains exhibiting in vitro susceptibility to ticarcillin rose from 45.5% in 1987 to 59% in 1988 and 86% in 1989. Concomitantly, the proportion of P. aeruginosa strains simultaneously resistant to ticarcillin, piperacillin, cefsulodine and ceftazidime fell from 32% to 18.5% then 0%. A statistically significant correlation was found between the decrease in piperacillin use and the fall in penicillinase-producing ticarcillin-resistant strains of P. aeruginosa. Because piperacillin has undesirable effects on the intestinal flora and promotes the emergence of resistant strains of P. aeruginosa, the authors now use narrow spectrum antimicrobial agents as first line treatment of nocosomial infections.

The purpose of this multicentre open trial carried out in 286 patients (mean age: 58 +/- 17 years) was to evaluate the effectiveness of imipenem-cilastatin in the treatment of severe infections observed in intensive care units. In more than 90 per cent of the cases an underlying pathology was present before the infection, and 41 per cent of the patients had previously been operated upon. Respiratory tract infections and septicaemias accounted for 75 per cent of the cases. The infection had been present for 7.1 +/- 8.2 days before treatment was instituted, and in 66 per cent of the cases it was nosocomial. The frequency of prolonged artificial ventilation (198 cases) demonstrated the severity of these infections. Seventy-three per cent of the initial 622 isolates were Gram-negative bacilli; the responsible organisms were Pseudomonas aeruginosa in 106 cases and Acinetobacter in 76 cases. Imipenem-cilastatin was administered alone in 173 cases and combined with other antibiotics in 113 cases. The mean dosage and duration of treatment were 29.2 +/- 9.9 mg.kg-1 and 13.4 +/- 7 days respectively. Clinical cure or improvement was achieved in 244 out of 284 assessable patients (65.2 per cent). Among the 40 therapeutic failures, 16 were due to a resistant organism isolated during treatment (P. aeruginosa 10, P. maltophilia 6). These good or very good clinical results show that imipenem is effective in the treatment of severe infections observed in intensive care units.

In a multicentre open therapeutic trial, 85 patients (57 men, 28 women; mean age: 58 +/- 18 years) were treated for documented bacterial infection with imipenem-cilastatin administered alone (65 patients) or combined with another antibiotic (20 patients). One or several underlying diseases were present in 95 per cent of the cases; 83.5 per cent of the patients were under artificial ventilation. The infections treated were septicaemia (35 case), lower respiratory tract infection (37 cases), acute peritoneal infection (6 cases) and miscellaneous infections (5 cases). The majority of responsible organisms (69.4 per cent) were Gram-negative bacilli. Several organisms were responsible for 44.6 per cent of the infections. Clinical cure was obtained in 82.4 per cent of the patients, and 79 per cent of the strains were eradicated. Resistance to imipenem during treatment was observed in 9 cases and concerned 24 per cent of the Pseudomonas spp. strains initially isolated. The drug was well tolerated both clinically and at laboratory examinations.

A multicentre open trial was conducted in 31 centres to evaluate the therapeutic and ecological impact of imipenem-cilastatin on patients admitted to infectious pathology departments. Two-hundred patients (mean age: 58 +/- 19.4 years) were included in the study. The predominant infections were septicaemia, severe urinary tract infections and lower respiratory tract infections. Most of the patients treated (188/200) had associated severity factors. The acute infectious episode had been present for 9.3 +/- 12.2 days before the drug was prescribed. In the majority of patients the infection was hospital-acquired. Two-hundred and fifteen out of the 298 initial bacterial isolates were Gram-negative bacilli. Imipenem-cilastatin was administered alone in 74.5 per cent of the patients during 14.1 days on average in doses of 30 mg/kg/day. The drug was given as first-choice treatment in 60 per cent of the cases and after failure of another antibiotic therapy in 40 per cent. Clinical cure was obtained in 180 of the 198 assessable patients. Among therapeutic failures, 4 were due to the emergence during treatment of an imipenem-resistant Pseudomonas aeruginosa, but 30 of the 42 strains of Pseudomonas isolated before treatment were eradicated. The therapeutic success rates were 100 per cent in intra-abdominal infections, 94 per cent in septicaemias, 97 per cent in urinary tract infections and 82 per cent in lower respiratory tract infections, this last figure being one of the highest recorded in clinical trials. Frequent colonization or superinfection were not encountered in this study. The incidence of phlebitis at the site of injection was 14 per cent.

In a multicentre, prospective, controlled trial 211 patients with suspected septicaemia or pneumonia were allocated at random to either imipenem-cilastatin 500 mg 8-hourly or cefotaxime 1 g 6-hourly combined with amikacin 5 mg/kg 8-hourly. The treatments were administered for at least 5 days. Seventy patients on imipenem and 70 patients on cefotaxime-amikacin were assessable for comparison. There were no statistically significant differences between the two groups in underlying pathology and in the clinical results obtained: septicaemia 20/26 patients of the imipenem group and 20/25 patients of the cefotaxime-amikacin group were cured; pneumonia 38/44 patients of the imipenem group and 34/45 patients of the cefotaxime-amikacin group were cured. There were also no differences in the initial organisms and in the bacteriological cure rate, except for Pseudomonas aeruginosa. At the moment, imipenem administered alone is as effective as the cefotaxime-amikacin combination in the treatment of septicaemia or pneumonia in intensive care patients, with the exception of P. aeruginosa pneumonia in patients under assisted ventilation.

One-hundred and ninety-nine patients with severe infection caused by susceptible organisms were treated with imipenem-cilastatin administered intravenously in doses of 31 mg/kg/day on average. The drug was given alone in 71 per cent of the cases and with another antibiotic (usually an aminoglycoside) in 13 per cent. In 57.4 per cent of the patients several micro-organisms were involved. Clinical success was achieved in 169 patients (84.9 per cent), 129 of whom (64.8 per cent) were cured and 40 (20.1 per cent) were improved. Failure was observed in 30 patients (15.0 per cent). Fifteen patients died during treatment; death was directly related to the infection in 5 and occurred while the infection had clinically regressed in 5; in the remaining 5 patients persistence of the infection played a determinant role in the fatal outcome. In 15 patients the lack of clinical improvement under imipenem-cilastatin required by 5/65 Pseudomonas strains and 2/56 Anaerobes strains initially isolated, or to superinfection, or to persistence of the initial strain in the focus of infection. Treatment was discontinued in 8 cases due to adverse events (skin intolerance 4, thrombocytopenia 4). There was no statistically significant difference in the outcome of patients treated with imipenem-cilastatin alone or combined with another antibiotic.

The efficacy and tolerability of imipenem-cilastatin were studied in 66 haemato-oncology patients from 16 centres presenting with a bacteriologically proven infection; 29 of the patients had neutropenia (less than 500/sq.mm). The drug was given as monotherapy in 30 cases, as bitherapy in 29 cases and as tritherapy in 7 cases. The initial clinical diagnosis was septicaemia in 29 patients, various severe infections in 31 and fever of unknown origin in 6. The infection was bacteriologically documented in 55 patients; the remaining 11 patients were kept in the study and the results of their treatment were taken into account. One-hundred and fourteen bacterial strains were isolated, including 64 Gram-negative organisms, 48 Gram-negative organisms and 2 anaerobes. Treatment was discontinued in 4 patients, due to lack of response in 2 and to adverse events (haemolytic shock, Lyell's syndrome) in 2. Five patients died during the study: 4 of an underlying pathology, the infection having subsided, and 1 of persistent infection and the above-mentioned Lyell's syndrome. Clinical success was achieved in 63 patients (95.5 per cent), including 27 of the 29 patients with neutropenia (93.1 per cent). Among the 114 strains isolated, 106 were eradicated, 5 persisted and only 1 became resistant (outcome not available in 10 cases). Apart from the haemolytic shock and Lyell's syndrome, haematological and hepatic alterations were minor and not obviously due to imipenem-cilastatin. Three cases of colonization and 3 cases of superinfection were recorded during the study.

Imipenem, a new carbapenem (thienamycin) beta lactam antibiotic which is clinically used in a 1:1 combination with cilastatin, an inhibitor or renal metabolism of imipenem, was evaluated in 25 patients; 11 children and 14 neonates. A mean daily dose of 60 mg/kg was given to children and the dose in neonates was 50 mg/kg. Clinically, 21 patients were cured, two failed to respond to treatment and two were not evaluable. Pharmacokinetic studies were performed in the 11 children and in 10 of the neonates. The mean elimination half-life of imipenem was 0.87 h in children and 2.1 h in neonates. The mean cilastatin elimination half-life was 0.73 h in children and 5.1 h in neonates. This difference in half-life between children and neonates is similar to the one noted between healthy adults and adults with renal insufficiency. No accumulation of imipenem was seen in neonates studied on the first and fifth days of treatment.

Twenty two patients (mean age: 69 years) undergoing cataract surgery were perfused with imipenem (1g for 1 hour). The samples of serum and aqueous humor were taken simultaneously 0.5-1-2-5-7 hours after the end of perfusion and immediately stabilized by MES or MOPS buffers and ethylene glycol. The antibiotic concentrations were determined with Bacillus subtilis ATCC 6633. Aqueous humor levels increased from the end of perfusion to 2nd hour (peak 5.2 mg/l) and decreased after (mean level 2.8 mg/l). The concentrations were well above MIC-90 of the species commonly involved in bacterial endophthalmitis. Imipenem appears to have an exceptional penetration into ocular fluids.