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Mycobacterium abscessusest une bactérie non tuberculeuse, environnementale, à croissance rapide, qui est responsable d’infections pulmonaires sévères, notamment chez les patients atteints de mucoviscidose. Le traitement actuel combine l’utilisation d’une b-lactamine et d’un aminoglycoside associés à un macrolide. Cette bactérie est polyrésistante à la plupart des antibiotiques utilisés en clinique. Les mécanismes de résistance, innés ou acquis, qu’elle a développés, conduisent fréquemment à des échecs thérapeutiques, ce qui limite considérablement les moyens de lutte disponibles pour le clinicien. Une compréhension globale des mécanismes de résistance de cette bactérie s’avère ainsi nécessaire pour contrer les infections pulmonaires qu’elle provoque.

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.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.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.

Carbapenems are the major weapons in the treatment of nosocomial infections. Since 1996, there have been an emergence and dissemination of carbapenem resistance in the world, especially among Enterobacteriaceae. Resistance is due to one or several mechanisms including production of carbapenemases. A prospective study was carried out from April to September 2011 at the Laboratory of Microbiology of Military Teaching Hospital in Rabat. The aim of this study was to search by phenotypic methods carbapenemases production in Klebsiella pneumoniae at Laboratory of Microbiology of the HMIMV of Rabat by disc diffusion for susceptibility to imipenem (IMP) and ertapenem (ETP), E-test and Hodge test; 211 strains of K. pneumoniae were analyzed. The samples were most frequently obtained from the urinary tract (63.8%); pus (16.5%) and blood cultures (11.8%); 27% of the strains produced extended spectrum of beta-lactamase (ESBL); 3 strains were resistant to ertapenem by disc diffusion. Investigations of these 3 strains in E-test shown that they were resistant to ertapenem but susceptible to imipenem. Tested by Hodge method, 3 strains gave repeatedly positive results. Thus, rate of K. pneumoniae producing KPC type in our study is 1.42%. Our study shows the evidence of K. pneumoniae type carbapenemase (KPC) in Military Teaching Hospital of Rabat. However, the gene encoding the type of resistance must be determined by molecular methods.

This study examines the activity of doripenem, a new carbapenem compound compared with amoxicillin-clavulanic acid, piperacillin+tazobactam, imipenem, clindamycin and metronidazole against 316 anaerobes.Inoculum preparation and agar dilution method were performed according to the CLSI method for anaerobes (M11A7).At a concentration of 4μg/ml doripenem and imipenem (IMP) inhibited 122 (96 %) and 126 (99 %) strains of the Bacteroides fragilis group, respectively. In contrast, doripenem appeared more potent than IMP against Gram-positive anaerobes inhibiting at the same concentration of 4μg/ml 145/145 strains (100 %) versus 115/145 for IMP (79.3 %). Against 316 anaerobic strains, the carbapenem doripenem had an MIC(50) of 0.25μg/ml and an MIC(90) of 2μg/ml. Results were similar to those for imipenem (MIC(50) of 0.125μg/ml and MIC(90) of 4μg/ml). If we consider the resistant breakpoints of the two carbapenems as defined by EUCAST, the resistance rate for doripenem (MIC4μg/ml) 1.6 % is similar to that of imipenem (MIC8μg/ml) 1.3 %.Thus independently of the PK/PD parameters the two carbapenems demonstrated very close activity; doripenem was more potent on Gram-positive anaerobes and slightly less potent against Gram-negative anaerobes mainly the B. fragilis group. Further clinical studies are needed to assess its usefulness in patients.

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.

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.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.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.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.

Controlling antibiotic resistance of bacteria is a priority for public healthcare.This study concerned the frequency of multidrug resistant bacteria (MDRB) in a Tunisian Hospital with the aim of establishing guidelines for MDRB prevention.The study was conducted during two years (1 January 2005-31 December 2006). Samples collected for the clinical diagnostic were included. The MDRB concerned were: methicillin resistant Staphylococcus aureus(MRSA), Enterobacteriacae resistant to of third generation cephalosporin (ER3GC), Acinetobacter baumannii resistant to both imipenem and ceftazidime, Pseudomonas aeruginosa resistant to both imipenem and ceftazidime.During the study period, 2475 bacteria were tested by disk diffusion. 597 MDRB were collected, the rate of MBR was 24.1%. These MDRB were mainly recovered in burn unit (82.6%). ER3GC (47%) and MRSA (29,2%) were the most frequent MDRB. A. baumannii and P. aeruginosa multiresistant concerned 14,8% and 9% of MDRB. MDRB were isolated mainly from blood cultures (45%). The rate of MRSA was 46.4% among 375 strains of S. aureus. ER3GC represented 25,6% among 1096 isolates. Concerning A. baumannii and P. aeruginosa, 51.7% and 20.5% were resistant to both imipenem and ceftazidime among 170 and 264 isolates. Antibiotic resistance evolution showed a decrease of resistance in 2006 versus 2005. This decrease should be explained by the improvement of hygiene measure especially hand washing with the introduction of hydro- alcoholic solutions, a better targeted antibiotherapy promoted by a close cooperation between microbiologists and clinicians.The MDRB were frequent in our hospital. They were mainly isolated from the burn department. The measures of prevention already implemented are effective and must be strengthened with the continuous surveillance of MDRB.

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.

We report a 40-year-old kidney recipient who developed disseminated nocardiosis associated with cutaneous Kaposi's sarcoma. The withdrawal of immunosuppressive therapy and prolonged antibiotic therapy, including imipenem and trimethoprim-sulfamethoxazole, resulted in a favourable outcome of both disorders. Three years later, graft function remains stable with a complete regression of skin and pulmonary abnormalities. This case report illustrates the predisposing role of immunosuppressive treatment in the occurrence of infectious and neoplastic complications observed after solid-organ transplantation.

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.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.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.

to characterize epidemiological and clinical features related to the multi-drug Acinetobacter baumannii infections in the university hospital Sahloul in Tunisia.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.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.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.

Investigation of an outbreak caused by an imipenem-resistant Pseudomonas aeruginosa strain and research of its hospital reservoir.Nine strains isolated from protected tracheal specimens during 14 weeks (October 2004 to January 2005) from 8 infants, and one strain from vacuum interrupter were studied. Epidemiological study was investigated by determination of antibiotics susceptibility, serotyping and Pulsed-field gel electrophoresis (PFGE).Strains were of O:12 serotype, they have the same antibiotype characterised by imipenem resistance. Strains were indistinguishable or closely related as determined by PFGE. The common source of P. aeruginosa O:12 strains was not determined, however eradication of the epidemic strain was obtained by amelioration of hygiene conditions and the change of disinfectors.Outbreak of respiratory infections due to an imipenem-resistant P. aeruginosa O:12. The common source of the epidemic strain was not determined.

Metallo-beta-lactamases (MBL) are enzymes produced by Gram-negative bacilli such as Pseudomonas aeruginosa and Acinetobacter baumannii. These enzymes make these isolates resistant to imipenem.The aim of this study was to determine the prevalence of this resistance mechanism in Pseudomonas aeruginosa and Acinetobacter baumannii strains identified in the bacteriology laboratory of the Rabat Ibn Sina teaching hospital, Morocco.Screening for MBL was systematic in all resistant strains and/or strains with decreased sensitivity to imipenem, according to Dongeun Yong et al.'s method, using a sterilized solution of EDTA 0.5 M pH 8.Eighty-five bacterial strains (48 P. aeruginosa and 37 A. baumannii) were identified 23% (11) and 57% (21) of which were respectively resistant to the imipenem. The prevalence of MbetaL producing strains was 27% for P. aeruginosa and 38% for A. baumannii.These results show that the frequency of these strains is increases in our hospital and that their emergence represents a serious therapeutic and epidemiological problem. This means that we need to implement the supervision of hospital microbial environment and strictly apply hygiene measures.

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.

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.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.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.

A 32-year-old patient taking corticosteroid therapy for 10 months for autoimmune hemolytic anemia developed Hodgkin's disease and concomitant acute pulmonary nocardiosis. After treatment with imipenen and amikacin for 15 days, which was adapted to susceptibility tests, multiple-drug chemotherapy using the ABVD protocol (doxorubicin, bléomycin, vinblastine, dacarbazine) was given without recurrence of the pulmonary infection. Antibiotic prophylaxis using a minocycine-erythromycin combination was continued for 8 months. We discuss the importance of long-term treatment based on data in the literature.

Bacterial intracerebral aneurysms, which are a common complication of infectious endocarditis, are unusual without Osler's disease.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.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.

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.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.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.

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.

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.

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.

Meropenem is a new dehydropeptidase stable carbapenem which has an in vitro bacteriostatic activity superior to imipenem against Pseudomonas aeruginosa. Minimal inhibitory concentrations of meropenem (MEM) and imipenem (IPM) were determined on twelve strains: two were genetically characterized reference strains and ten isolated from patients. Killing curves were performed for MEM used at 1,2 and 4 fold the MIC and 32 mg/l; survivors were counted at baseline and after 5 and 24 hours of incubation by spiral plating. Five strains were susceptible to MEM and IPM; five were intermediate and two resistant to MEM; these seven strains were resistant to IPM. A weak bactericidal effect was obtained after 5 h at each concentration. Only one strain achieved a 3 log 10 reduction after 5 h at 2 x MIC. A regrowth of all the strains tested was observed after 24 h.

The in vitro activity of two new beta-lactam agents, cefpirome (CPO) and cefepime (FEP), was investigated against 295 Gram-negative bacilli (250 enterobacteriaceae and 45 P. aeruginosa) isolated from neutropenic patients. They were compared with ceftazidime (CAZ), piperacillin-tazobactam (TZP), imipenem (IPM) and cefotaxime (CTX). All enterobacteriacae were susceptible to IPM, 16 strains were intermediately susceptible or resistant to CAZ (1 strain of E. coli, 4 of Morganella morganii and 11 of Enterobacter. The 250 strains of enterobacteriacea were susceptible to FEP (MIC1 mg/l) and only one strain among them was intermediately susceptible to CPO. Among 45 strains of P. aeruginosa, 21 strains were susceptible to CPO, 30 to FEP, 31 to TZP, 32 to CAZ and 34 to IPM. All the strains were inhibited by less than 32 mg/l of FEP and IPM.

During 1994, the in vitro antibiotic susceptibility of 306 anaerobic bacteria was performed in 4 hospitals, by the reference agar dilution method. Among the 129 B. fragilis group strains, only two B. fragilis strains were resistant to the three carbapenems and all beta-lactams, even combined with beta-lactamase-inhibitors while metronidazole resistance could not be detected. Evolution in antibiotic resistance rates could be assessed only for piperacillin whose resistance rates increased to 20%. beta-lactamase production was detected respectively for 27% of Prevotella and 17% of Fusobacterium strains. No beta-lactamase activity was seen among Gram positive anaerobes. On the whole anaerobic strains resistance rates were: biapenem, imipenem, meropenem and piperacillin-tazobactam 0.7, amoxicillin-clavulanic acid or metronidazole 2, piperacillin 11.3, amoxicillin 31%, respectively. The three carbapenems demonstrated a good in vitro activity against most anaerobes with few differences between them.

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.

Increasing resistance to multiple antimicrobial agents including penicillins is a current problem with Streptococcus pneumoniae. Seven cases of severe infection due to penicillin G-resistant pneumococci were seen in two teaching hospitals in Paris (France) during the first half of 1991; six of the strains were recovered from pulmonary secretions (protected brush specimens) and one from cerebrospinal fluid (CSF). The bacteriostatic activity and killing curves of eight antimicrobials against these seven strains were studied. Antimicrobial agents tested included penicillin G (PEN), amoxicillin (AMX), cefotaxime (CTX), imipenem (IPM), rifampin (RIF), vancomycin (VAN), fosfomycin (FOS), and erythromycin (ERO). MICs were determined using the agar dilution method. Killing curves were obtained using a liquid medium inoculated with 10(5) to 10(6) CFU/ml and subjected to continuous agitation; survivors were counted at baseline and after 1, 3 and 5 hours incubation. MICs of each antimicrobial (mg/l) for the seven strains were in the following ranges: PEN: 0.5-2, AMX: 0.5-2; CTX: 0.125-1; IPM: 0.03-0.25; RIF: 0.12-0.25; VAN: 0.25-1; FOS: 16; ERO: 0.06 greater than 4. Overall, bactericidal activity was greatest with vancomycin, followed by imipenem, then amoxicillin. The cefotaxime-fosfomycin combination proved synergistic and exhibited bactericidal activity (2MIC + 2MIC) for three of the seven strains. This study demonstrated the value of the cefotaxime-fosfomycin combination. Both these antimicrobials seem appropriate for the treatment of meningitis caused by penicillin G-resistant pneumococci provided their dosage is adjusted to achieve adequate drug levels in the cerebrospinal fluid.

A characteristic feature of imipenem-resistant strains of Pseudomonas aeruginosa is loss or decreased expression of the outer membrane protein (OMP) D2, whose molecular weight is 45 to 49 kDa. D2 was studied in 15 strains of P. aeruginosa with intermediate susceptibility or resistance to imipenem recovered from the sputum of 15 patients with cystic fibrosis. The OMP was extracted using Sarkosyl and separated by SDS-PAGE electrophoresis. Electrophoresis patterns were compared to those of reference strains 3B and 3C which are resistant and susceptible to imipenem, respectively. Expression of D2 was normal in three strains, weak or very weak in 11 strains and absent in one strain. For 12 strains, the alteration of the D2 protein was consistent with previous reports. However, the finding of normal D2 production in three strains is unusual and suggests the possible presence of another mechanism of resistance.

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.

Imipenem is a beta-lactam antibiotic active against most Gram-negative bacilli. Between July 1, 1987 and September 30, 1989 (9 semesters), the activity of imipenem against 6 micro-organisms was tested in two intensive care units attached to the university hospital of Caen (Normandy). During the same period, the consumption of imipenem was evaluated from the number of vials drawn by each of these two units from the central pharmacy. Imipenem was found to be 100 percent effective against 5 of the 6 micro-organisms tested, but transient falls in sensitivity and an increase in imipenem consumption were observed when Pseudomonas aeruginosa was the pathogen. The most probable cause of these transient decreases of imipenem activity against Ps. aeruginosa was the existence of a resistant strain which showed a protein abnormality in its outer membrane by temporary selection pressure.

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.