Resistance of uropathogens in symptomatic urinary tract infections in León, Nicaragua.

Management of urinary tract infections (UTI) in Central America and especially Nicaragua, is complicated by the lack of knowledge about the antibiotic resistance of uropathogens. We conducted a prevalence study to gain more insight into the aetiology, bacterial resistance and risk factors for symptomatic UTI in the region of León, Nicaragua. In 2002, all consecutive patients with UTI symptoms and pyuria >/=10 WBC/hpf were admitted to the study. Positive cultures from midstream urine specimens were defined as >/=10(5) cfu/ml of a single uropathogen. Susceptibility tests were performed with disc diffusion tests using the Kirby-Bauer method and broth microdilution using National Committee for Clinical Laboratory Standards criteria both in León and a reference laboratory in Utrecht. A positive culture was present in 62 of 208 study subjects (30%). Escherichia coli (56%), Klebsiella spp. (18%) and Enterobacter spp. (11%) were the most frequent pathogens isolated. Presence of cystocele, incontinence and increasing age were risk factors for bacterial UTI. E. coli was least resistant to ceftriaxone, amikacin and nitrofurantoin (>90% susceptible). We observed high resistance rates in E. coli to amoxicillin (82%, MIC(90) 128 mg/l), trimethoprim-sulphamethoxazole (TMP-SMX) (64%, MIC(90) 32 mg/l), cephalothin (58%, MIC(90), 32 mg/l), ciprofloxacin (30%; MIC(90), 32 mg/l), amoxicillin/clavulanate (21%, MIC(90) 8 mg/l) and gentamicin (12%, MIC(90) 2 mg/l). Our results suggests that community acquired uropathogens in Nicaragua are highly resistant to many antimicrobial agents. The use of amoxicillin, trimethoprim-sulphamethoxazole and cephalothin against uropathogens needs to be reconsidered. High quinolone resistance rates among E. coli in Nicaragua gives cause for great concern.

Do cultures contribute to optimisation of antibiotic therapy in the intensive care unit?

Obtaining diagnostic microbiological cultures before initiating empirical antimicrobial therapy is part of the diagnostic work-up of intensive care patients with a clinical suspicion of infection. However, it is unknown to what extent these cultures provide a microbiological cause of infection and to what extent antimicrobial therapy is influenced. During a 6-month period, all episodes of suspected clinical infection were analysed and categorised as non-microbiologically proven infection (non-MPI) or MPI. Effects of culture results on antibiotic therapy were analysed for episodes of respiratory tract infection. Invasive diagnostic techniques were not routinely used for diagnosis of respiratory tract infections. Among 212 patients admitted, 147 episodes of clinical suspicion of infection were recorded (104 for respiratory tract infection) and 1147 microbiological cultures were obtained (0.64 culture per patient day). Antibiotics were administered on 1111 (62%) of 1803 patients days. Of the respiratory tract infections, 571 cultures resulted in 49 (47%) MPI. Cover with empirical antibiotics was inappropriate in 7 of 104 cases (8%) of respiratory infections. In 12 cases (11.5%) empirical therapy could have been changed based on culture results. Negative cultures were never followed by cessation of therapy, but the duration of treatment was significantly shorter for non-MPI. Forty-seven percent of respiratory tract infections were microbiologically confirmed and, based on culture results, empirical antimicrobial therapy could have been influenced in 11.5% of cases of respiratory tract infections. These findings provide aspects to evaluate and improve the diagnostic work-up of infections in the ICU.

Early infections in adults undergoing matched related and matched unrelated/mismatched donor stem cell transplantation: a comparison of incidence.

We compared the incidence of early infectious complications between matched related (MR) and matched unrelated/mismatched (MU/MM) allogeneic stem cell transplant (allo-SCT) recipients in a single centre over a 6-year period in 214 consecutive adult patients. Early infections were defined as occurring from hospital admission for SCT until discharge. One hundred and fifty-nine patients received an allograft from MR donors and 55 patients received MU/MM allo-SCT. One hundred and eight of 214 patients had 147 episodes of fever. Ninety-three episodes (63%) were due to clinically or microbiologically documented infections and 54 episodes (37%) to fever not related to infection. Patients undergoing MU/MM transplantation tended to have more documented infections compared to recipients of MR allo-SCT (P = 0.06). Significantly more MU/MM transplant recipients had breakthrough infections with Herpes simplex virus type 1 (HSV-1, P = 0.003), and more CMV reactivation (P = 0.015). The mortality rate in all patients during hospitalisation post-SCT was 6.3% in MR and 18.2% in MU/MM allo-SCT recipients (P = 0.009). Early mortality was associated with infection in 70% of the patients, with a similar distribution between MR and MU/MM transplant recipients. However, MU/MM transplant recipients had significantly more early deaths due to toxic causes (P < 0.001). We conclude that early post-transplant MU/MM transplant recipients tend to have more documented infections, and have significantly more breakthrough infections with HSV-1 and more CMV reactivation. MU/MM transplant recipients are at higher risk of early mortality, especially due to toxic causes.

Double-blind, placebo-controlled study comparing the effect of azithromycin with clarithromycin on oropharyngeal and bowel microflora in volunteers.

The purpose of this double-blind study was to assess the effect of azithromycin and clarithromycin on oral and fecal microflora. Bacterial species from fecal samples and throat washes from healthy volunteers were identified and quantified before, during and after receipt of either placebo ( n=6), azithromycin (500 mg once daily for 3 days; n=6) or clarithromycin (500 mg twice daily for 7 days; n=6). In both antibiotic groups, the changes in oropharyngeal aerobic microflora following antibiotic administration were minor. Antibiotics neither changed the bacterial load of Streptococcus spp. compared with placebo, nor did macrolide-resistant streptococci emerge. In the fecal aerobic microflora, the number of organisms of the family Enterobacteriaceae decreased slightly after antibiotic administration in both the clarithromycin and the azithromycin groups, but levels normalized by day 21 after therapy. No colonization with nonfermenters or Clostridium difficile was seen, and the total number of anaerobic bacteria was not affected in any study group. In conclusion, there were no significant differences between azithromycin and clarithromycin in their effect on human oropharyngeal and intestinal microflora, nor was the use of these antibiotics associated with colonization by resistant, gram-positive organisms or overgrowth of opportunistic microorganisms.

Infectious gastro-enteritis: an uncommon cause of diarrhoea in adult allogeneic and autologous stem cell transplant recipients.

The incidence and aetiology of acute diarrhoea in 60 adult allogeneic or autologous stem cell transplant (SCT) recipients was determined in a prospective study. Stool specimens were obtained prior to SCT and on days +20, +40, +60 and +100 post transplant. Microbiological evaluation was performed for pathogenic bacteria, fungi, parasites and viruses. Forty-seven patients were evaluable of whom 31 had a total of 48 acute diarrhoeal episodes. Diarrhoea occurred in 79% of allogeneic and 47% of autologous SCT recipients (P < 0.05). Intestinal infections were found in three of 48 (6%) diarrhoeal episodes. Clostridium difficile with positive toxin was cultured twice and one stool specimen was positive for cryptosporidium. Intestinal pathogens were identified in 13 out of 172 stool specimens from asymptomatic patients and included: rotavirus (4), adenovirus (3), C. difficile, toxin positive (2), and others (4). Graft-versus-host disease was confirmed by biopsy in two of 36 episodes of diarrhoea in allogeneic patients, and in three patients a relationship between reactivation of cytomegalovirus and diarrhoea was suspected. In 40 of 48 (83%) episodes of diarrhoea no clear aetiology could be found.

Oerskovia xanthineolytica: a new pathogen in bone marrow transplantation.

A 53-year-old woman with non-Hodgkin lymphoma underwent an autologous bone marrow transplant (BMT). Incomplete reconstitution necessitated the use of a long-term central venous catheter. One year after BMT she presented with fever. Echocardiography revealed vegetations on the tricuspid valve. Gram-positive rods grown from blood cultures and catheter tip were identified as Oerskovia xanthineolytica. We report the first case of native valve endocarditis caused by this organism.

Detection of antigen in sera of patients with invasive aspergillosis: intra- and interlaboratory reproducibility. The Dutch Interuniversity Working Party for Invasive Mycoses.

The intra- and interlaboratory reproducibilities of a commercial sandwich enzyme-linked immunosorbent assay (ELISA) for the detection of Aspergillus galactomannan in serum (Platelia Aspergillus; Sanofi Diagnostics Pasteur, Marnes-La-Coquette, France) were evaluated in six laboratories of university hospitals. Twenty serum samples were obtained from 12 neutropenic patients including 6 with invasive aspergillosis. These samples were blinded and sent to each center together with eight blinded ELISA-negative serum samples spiked with known concentrations of galactomannan. The centers were provided with ELISA microtiter plates from a single batch and a detailed protocol. Ten clinical samples showed ELISA reactivity, while 10 samples were ELISA negative. The mean coefficient of variation (CV) of the optical density values was 4.24% within a single assay and 25.6% between runs. The interassay CV of the ratios for the serum samples tested was 18.6%. Analysis of ordinal interpretation of the ELISA result (i.e., negative, gray zone, or positive) showed excellent reproducibility. Recalculation of the cutoff values for positive and negative samples suggested that the cutoff level recommended by the manufacturer could be lowered from 1.0 to 0.8 for negative samples and from 1.5 to 1.0 for positive samples. The intra- and interlaboratory reproducibilities were excellent when the ELISA results were interpreted as ordinal data, but considerable variation in optical density values and, to a lesser extent, in the ratios for the serum samples tested, was observed between runs. High assay variability was also found for serum samples spiked with known concentrations of galactomannan. Therefore, antigen titers in serum samples from a single patient, measured in different runs, should be compared with caution.

A double-blind, placebo-controlled, parallel group study of oral trovafloxacin on bowel microflora in healthy male volunteers.

BACKGROUND: Treatment with oral antibiotic drugs generally influences normal fecal flora. These changes can be both beneficial (eg, elimination of aerobic, gram-negative bacilli) and detrimental (eg, the appearance of resistant pathogenic micro-organisms). Trovafloxacin, a new fluoroquinolone with in vitro activity against anaerobes, and gram-negative, gram-positive, and atypical pathogens, is a potentially beneficial antimicrobial for bowel sterilization. This double-blind trial investigated the effect of trovafloxacin on the normal microbial bowel flora of healthy male subjects. METHODS: Subjects were randomized (in a 2:1 ratio) to receive either 200 mg trovafloxacin once daily for 10 days or a matching placebo. Fecal samples were collected at two baseline occasions, on visit days 4, 7, 10, and 17, and at follow-up. Bacterial species were identified and quantified in the fecal samples. RESULTS: Twelve subjects received the active drug and seven received placebo. No Enterobacteriaceae were found in samples from days 4 to 10 in subjects receiving trovafloxacin. No changes in Enterobacteriaceae were found throughout the study in subjects receiving placebo. Incidental Enterobacteriaceae were isolated from subjects in the trovafloxacin group at the end of the study. No clinically significant differences were found in either group with respect to prevalence, appearance, or disappearance of aerobic gram-positive cocci, anaerobic bacteria, or yeasts. All tested Enterobacteriaceae were highly susceptible to trovafloxacin. No increase in minimum inhibitory concentration values was seen in day 17 and follow-up samples for isolated Escherichia coli strains. No Clostridium difficile was found in day 17 or follow-up samples from subjects in the trovafloxacin group. All tests for clostridium toxin were negative. CONCLUSIONS: During the treatment period, E. coli could not be cultured from the feces of the 12 healthy subjects receiving 200 mg trovafloxacin daily during days 4 to 10. All isolated Enterobacteriaceae were susceptible to trovafloxacin and no changes in susceptibility were found after the treatment period. In subjects treated with trovafloxacin, the prevalence and number of gram-positive bacteria were rapidly reduced. Trovafloxacin is able to selectively and reversibly suppress bowel flora.

A risk-adapted approach with a short course of ganciclovir to prevent cytomegalovirus (CMV) pneumonia in CMV-seropositive recipients of allogeneic bone marrow transplants.

We studied the efficacy and safety of a risk-adapted approach with ganciclovir to prevent cytomegalovirus (CMV) pneumonia in 41 CMV-seropositive recipients of genotypically human leukocyte antigen-identical bone marrow transplants. Prophylaxis with ganciclovir, at a dosage of 2.5 mg/kg twice a day for 14 days, was started when patients were treated with high-dose steroids for acute graft-versus-host disease (i.e., they were considered at high risk for CMV pneumonia), or the drug was given as preemptive therapy when CMV antigenemia developed (i.e., the patients were considered at intermediate risk for CMV pneumonia). Twelve patients (29%) were treated prophylactically and seven patients (17%) preemptively. Only five patients (26%) received a second course of ganciclovir (given preemptively to four patients). Twenty-two patients (54%) never received ganciclovir because they did not fall within these risk groups. None of the 41 patients developed CMV pneumonia. Ganciclovir-related granulocytopenia did not occur (course 1) or was very mild (course 2). We conclude that this approach appears to prevent the development of CMV pneumonia after bone marrow transplantation.

[Mycobacterium avium infection in HIV-infected patients: epidemiology, diagnosis, prevention and treatment]. / Mycobacterium avium-infectie bij HIV-geïnfecteerde patiënten: epidemiologie, diagnose, profylaxe en behandeling.

The prevalence of infection with Mycobacterium avium complex (MAC) has increased since the outbreak of the HIV pandemic. This complex comprises two organisms: M. avium (mostly) and M. intracellulare (rarely). The source of MAC infection is not known. The principal risk factors for disseminated MAC infection in a patient with HIV infection are a low CD4 count and a previous opportunistic infection. The symptoms of disseminated MAC infection resemble those of HIV wasting; a positive culture of normally sterile tissue confirms a MAC infection. There is reserve with regard to routine prophylaxis in HIV-infected persons because of the possible development of resistance, interaction with other drugs used in AIDS, toxicity and possible absorption disorders which might cause prophylaxis to fail. For the treatment of disseminated MAC infection, a combination of at least two medicaments (macrolides and ethambutol) is recommended.

A short (3-day) course of azithromycin tablets versus a 10-day course of amoxycillin-clavulanic acid (co-amoxiclav) in the treatment of adults with lower respiratory tract infections and effects on long-term outcome.

The efficacy and safety of a 3-day regimen of azithromycin prescribed in the new tablet form and of a 10-day regimen of amoxycillin clavulanic acid (co-amoxiclav, Augmentin) were compared in patients with acute lower respiratory tract infections. Of the 144 enrolled patients, 123 had a Type 1 acute exacerbation of chronic bronchitis (AECB), three patients had pneumonia, and 18 had purulent bronchitis. Treatment was successful, defined as cure or major improvement on day 14, in 59/62 (95%) patients in the azithromycin treatment group compared with 54/61 (90%) patients in the co-amoxiclav. At 30 days, the incidence of success was 77% (48/62) in the azithromycin treated group, compared with 66% (40/61) of co-amoxiclav-treated patients. At 60 days, incidences were 66% (41/62) and 59% (36/61), respectively. Several pathogens were isolated: Haemophilus influenzae in 21 patients (minimum inhibitory concentration (MIC) range for azithromycin 0.12-4 mg/l; co-amoxiclav 0.25-4 mg/l); Streptococcus pneumoniae in nine (MIC azithromycin < or = 0.06 > or = 256 mg/l; co-amoxiclav < or = 0.06-1 mg/l); and Moraxella catarrhalis in 11 (MIC azithromycin < or =0.06-2 mg/l; co-amoxiclav < or = 0.06-0.5 mg/l). Microbiological response rates were comparable. A significant correlation between clinical and microbiological cure was found (p = 0.02, power 0.6). In 15 (10%) patients, positive serology for viruses or atypical pathogens was found. In the co-amoxiclav-treatment group, 24 patients had mild adverse events (12 diarrhoea), compared with 27 treated with azithromycin (p = 0.47). It is concluded that a 3-day regimen of azithromycin prescribed as tablets is as clinically and microbiologically effective as a 10-day regimen of co-amoxiclav in the treatment of acute lower respiratory tract infections. Moreover, since the percentage of viral infections was low and a significant correlation between microbiological and clinical cure was found, this study shows that clinical symptoms can be used to establish which patients with AECB (Type 1) should be treated with antimicrobial agents.

Allogeneic bone marrow transplantation can restore CD4+ T-lymphocyte count and immune function in idiopathic CD4+ T-lymphocytopenia.

CD4+ T-lymphocytopenia in the absence of HIV infection is a heterogeneous disorder of unknown cause. Here we report a patient with idiopathic CD4+ T-lymphocytopenia, presenting with an opportunistic Rhodococcus equi infection. When aplastic anemia developed subsequently, allogeneic bone marrow transplantation was performed. Complete restoration of immune function was observed. We conclude that allogeneic bone marrow transplantation presents a potentially curative therapy for CD4+ T-lymphocytopenia.

Discontinuation of intravenous antibiotic therapy during persistent neutropenia in patients receiving prophylaxis with oral ciprofloxacin.

To evaluate the mortality and morbidity associated with early discontinuation of intravenously administered antibiotics, we prospectively examined the incidence and cause of recurrent fever in patients with persistent neutropenia who responded to a short course of intravenous antibiotic therapy. Preventive measures included the use of oral ciprofloxacin as prophylaxis for infection by gram-negative bacteria during the entire neutropenic episode. The rate of response to either initial or modified intravenous antibiotic therapy was 96% (149 of 156 episodes of fever). Eighty-five patients had an episode of persistent neutropenia (median duration, 7 days; range, 1-36 days) after they responded to treatment. Seven of these patients had recurrent fever, including 2 with bacteriologically documented infections, 4 with probable fungal pneumonia, and 1 with documented pneumonia due to Aspergillus fumigatus. Two patients with probable fungal pneumonia died, while the other infectious episodes resolved completely. These results do not support the continuation of intravenous antibiotic therapy for febrile patients with persistent neutropenia who have responded to the antibiotic regimen while receiving prophylaxis with oral ciprofloxacin.

[Rhodococcus equi pneumonia in patients with immunodeficiency]. / Rhodococcus equi-pneumonie bij patiënten met een afweerstoornis.

In three patients, men of 30, 21 and 24 years old respectively, Rhodococcus equi pneumonia was diagnosed. Antibiotic treatment, followed by secondary prophylaxis, was successful. In one patient, lobectomy was done. R. equi, a well-known bacterial pathogen in horses, appears also to be pathogenic in humans in case of immunodeficiency.

Infection prevention in autologous bone marrow transplantation and the role of protective isolation.

The efficacy of an antimicrobial regimen for prevention of infections was prospectively evaluated in 113 patients undergoing autologous bone marrow transplantation (BMT). Ciprofloxacin, 500 mg orally twice a day plus antifungal prophylaxis, fluconazole 50 mg once daily plus amphotericin B tablets or suspension and tablets, each 200 mg four times a day, was given. In addition all patients received streptococcal prophylaxis for 10 days after BMT. Documented infections occurred in 39% (44 of 113) of patients and unexplained fever in 27% (30 of 113). The efficacy of this regimen was reflected in a low mortality rate (3.5%) from infections and in the low need for intravenous amphotericin B (7%). No benefit of protective isolation was found in 59 patients compared with 54 patients treated without isolation measures.

Cefepime compared with ceftazidime as initial therapy for serious bacterial infections and sepsis syndrome.

In an open randomized multicenter comparative study, we evaluated the safety and efficacy of cefepime (CP; 2.0 g given intravenously every 12 h) and ceftazidime (CZ; 2.0 g given intravenously every 8 h) as initial treatment for adult patients with suspected serious bacterial infections. A total of 133 patients entered the study, of whom 114 were evaluable for clinical and microbiological response assessment: 56 received CP and 58 received CZ. About 50% (30 who received CP and 25 who received CZ) fulfilled the criteria of the sepsis syndrome. The treatment groups were comparable with respect to sex distribution, mean age, underlying diseases, treatment duration, APACHE II score, and type of infection. The most commonly cultured microorganisms were members of the family Enterobacteriaceae, Streptococcus pneumoniae, and Staphylococcus aureus. The causative microorganisms were eradicated from 92% (37 of 40) of patients with a microbiologically documented infection who underwent treatment with CP; they were eradicated from 86% (42 to 49) of patients who received CZ. The responses of only clinically documented infections in the CP group were 90% (27 of 30 patients); in the CZ group they were 87% (26 of 30 patients). When patients fulfilled the criteria of the sepsis syndrome (septic shock excluded), the causative microorganisms were eradicated from 89% (16 of 18) of CP-treated patients and 86% (12 of 14) of CZ-treated patients. None of these differences was statistically significant. Mortality was the same in both groups (four patients in each group) and was not attributable to the study medication. In conclusion, CP is at least as effective and as safe as CZ, as initial antimicrobial therapy for suspected serious bacterial infections in nonneutropenic patients with or without the sepsis syndrome. CP has the additional advantage in that it can be given twice daily, which may lead to a decrease in hospital costs.

Effect of loracarbef and amoxicillin on the oropharyngeal and intestinal microflora of patients with bronchitis.

The effect on the oropharyngeal and intestinal microflora and the efficacy and tolerance of loracarbef (200 mg b.i.d. for 7 days) versus amoxicillin (500 mg t.i.d. for 7 days) were compared in 80 patients with bronchitis. The oropharyngeal samples of 18% of patients in the amoxicillin group and 5% of patients in the loracarbef group revealed a new Gram-negative species around days 8-10. The presence of other aerobic bacteria than found at baseline in the faeces occurred in 38% of patients treated with amoxicillin compared with 31% in the loracarbef group on days 8-10. After treatment, no loracarbef- or amoxicillin-resistant aerobic Gram-negative bacteria were found in faecal samples in the loracarbef group, while amoxicillin- or loracarbef-resistant (E. coli) strains appeared in 35% of patients receiving amoxicillin (p < 0.001). Treatment success occurred by days 8-10 in all 40 patients receiving loracarbef, compared with 90% in the amoxicillin group, on days 21-28, in 93% and 90% respectively. The results of this study indicate that the use of loracarbef leads to minor changes in the normal oropharyngeal and intestinal microflora compared with amoxicillin, while almost no resistant Gram-negative bacteria emerge after treatment with loracarbef.