Prevalence of resistance-associated mutations in newly diagnosed HIV-1 patients in Greece.

The prevalence of HIV-1 drug resistance mutations in naïve patients has been previously shown to differ greatly with the geographic origin. The purpose of this study was to prospectively estimate the prevalence of HIV-1 drug resistance in Greece by analyzing a representative sample of newly HIV-1 diagnosed patients, as part of the SPREAD collaborative study. Protease (PR) and partial reverse transcriptase (RT) sequences were determined from 101 newly diagnosed HIV-1 patients, in Greece, during the period September 2002--August 2003, representing one-third of the total newly diagnosed HIV-1 patients in the same time period. The prevalence of HIV-1 drug resistance was estimated according to the IAS-USA mutation table taking into account all mutations in RT and only major mutations in PR region. The overall prevalence of resistance was 9% [95% confidence interval (CI): 4.2--16.2%]. The prevalence of mutations associated with resistance to NRTIs was 5% (95% CI: 1.6--11.2%), for NNRTIs was 4% (95% CI: 1.1--9.8%), while no major resistance mutations were found in PR. No multi-class resistance was detected in the study population. The prevalence of resistant mutations in the recent seroconverters was 22%. For two individuals, there was clear evidence for transmitted resistance based on epidemiological information for a known source of HIV-1 transmission. The prevalence of the HIV-1 non-B subtypes and recombinants was 52%.

Presence of human herpes virus-8 in saliva and non-lesional oral mucosa in HIV-infected and oncologic immunocompromised patients.

BACKGROUND/AIM: Human Herpes Virus-8 (HHV-8) is a recently identified virus etiologically associated with Kaposi's sarcoma. Studies regarding its presence in the oral cavity have given variable results. This study attempted to determine the oral presence of HHV-8 in an area where classic Kaposi's sarcoma is primarily found such as Greece. METHODS: Three groups of patients were studied: 10 immunocompromised with hematologic malignancies, 10 immunocompromised with HIV infection and 20 immunocompetent as controls. Whole unstimulated saliva and scrapes from the lingual and the buccal mucosa were collected and polymerase chain reaction was applied to amplify HHV-8 DNA. RESULTS: None of the patients in any group had oral lesions. In the control group, all samples tested negative (0/60). HHV-8 DNA was detected in 5/30 (17%) of all samples from HIV-positive patients (the mean value of their CD4+ T-lymphocytes being 385/mm3) and in 13/30 (43%) of all samples from oncologic patients (mean CD4+ T-lymphocytes 51/mm3). HHV-8 DNA was found in 10% of saliva samples and 40% of lingual and buccal scrapes both of HIV-infected and of oncologic patients. CONCLUSION: HHV-8 is present in the saliva and the non-lesional oral mucosa (not simultaneously) of patients with impaired immunity, with or without HIV co-infection. The oral epithelium seems to represent an independent location of viral residency and may be of viral replication; the clinical implications need further clarification.

Sequential antibiotic therapy for cost containment in the hospital setting: why not?

Antibiotic cost represents a significant part of hospital budgets all over the world. Restriction policies, however and other similar programmes intervening in antimicrobial prescribing have not always been successful in lowering antibiotic expenditure. Timely switch or sequential therapy from initial intravenous to subsequent equivalent oral treatment has been implemented in many institutions for the same purpose. Using strict criteria for optimum patient selection, switch therapy has been proven both effective as antimicrobial treatment and cost saving. As healthcare resources remain lower than needed, cost-saving policies become very desirable. Thus, switch therapy is expected to be more widely used, since it is a cost containing policy which does not compromise treatment outcome.

Impact of cefuroxime administration on endotoxin (LPS) and tumour necrosis factor-alpha (TNFalpha) blood levels in patients suffering from acute pyelonephritis: a preliminary report.

It has been suggested that treatment of systemic infections caused by Gram-negative bacteria with beta-lactam agents might add to the inflammatory process by resulting in the release of endotoxins (LPS) upon death of the Gram-negative bacteria. To evaluate that hypothesis, 25 patients with acute pyelonephritis of Gram-negative aetiology were given intravenous cefuroxime 1.5 g tid. Blood samples were collected at various time intervals for blood culture and for the determination of LPS, tumour necrosis factor-alpha (TNFalpha) and cefuroxime levels. LPS remained elevated at levels equal to those before the administration of cefuroxime over the first 24 h of therapy. A positive correlation was detected between LPS and drug levels 6 h after the initiation of therapy. Fever persisted in 50, 37.5 and 16.7% of patients 48, 72 and 96 h after the start of treatment, respectively, followed by a rise of LPS at levels above the baseline. Blood cultures taken at the same time were sterile. A wide range of TNFalpha levels were found at similar times of sampling, indicating that LPS triggers considerable TNFalpha production in the serum of some patients but not in others. It is concluded that antibiotic-induced endotoxaemia is a phenomenon that might be observed in patients receiving cefuroxime and that might be responsible for the persistence of fever despite negative blood cultures.

Asymptomatic bacteriuria of pregnancy: do obstetricians bother?

In view of the potentially serious consequences of asymptomatic bacteriuria of pregnancy (ASB), we surveyed the attitudes of Greek obstetricians towards this entity. A total of 108 obstetricians practicing in the area of Athens completed a questionnaire concerning ASB. Only 73 of the 108 stated that they screen their clients for ASB (51 of them when pyuria is present and only 22 in all pregnant women). Of special interest is the finding that a larger percentage of younger obstetricians (practicing for up to 9 years) habitually screen their patients, compared to older ones (83% vs 60%). Concerning treatment of ASB, only 45 out of 73 doctors screening for ASB give any treatment when ASB is present. Most obstetricians (87%) prefer a beta-lactam antibiotic. In almost all cases 7-10 days are considered the appropriate duration of treatment. Better education of obstetricians, especially the older ones, concerning detection and management of ASB is needed.

Enhanced in-vitro bactericidal activity of amikacin combined with latamoxef, cefotaxime and aztreonam against multi-resistant Enterobacter cloacae.

The in-vitro interactions of amikacin with latamoxef, cefotaxime and aztreonam were studied for 20 multiresistant strains of Enterobacter cloacae isolated from clinical specimens of nosocomial origin. All the strains were resistant to amikacin, cefotaxime and aztreonam while 14 were resistant and six sensitive to latamoxef. Interactions were studied simultaneously by the killing curve technique after exposure to 16 mg/l of each antibiotic, whenever the MIC was above 16 mg/l and 1/4 the MICs whenever the MIC was less than or equal to 16 mg/l. Enhanced killing was defined as a greater than or equal to 2 log increase in bactericidal effect after three or five and a half or 24 h incubation with both drugs, as compared to the single most effective antibiotic alone. Aztreonam enhanced the rate of killing by amikacin for 13 strains, latamoxef for 12 strains and cefotaxime for 11 strains. For seven strains, all interactions exhibited enhanced killing over time. No antagonism was observed. The interaction results were independent of the MICs as well as of the underlying resistance mechanism to either of the combined antibiotics. The significance of these in-vitro results requires confirmation in vivo.

Nosocomial consequences of antibiotic usage.

In 1979, seven years after introduction of gentamicin into the greek market, resistance in Pseudomonas aeruginosa rose in Laiko General Hospital to an incidence of 55% of the isolates. Gentamicin then was the first line antibiotic. In 1983, three years after amikacin was brought onto the market and while it represented 3/5 of all aminoglycoside consumption, resistance against it in strains of Pseudomonas rose suddenly to 23%. However, amikacin prescription was not restricted and, in 1985, resistance rate, including all aminoglycosides and the 3rd generation cephalosporins, exceeded 50%. By analysing all available data, it was evident that: Urine predominates in the isolation of multiresistant strains, while in 1/2 of bacteraemias amikacin-resistant strains are implicated. The ICU is the most common source of isolation and similar strains are spread in all hospital wards. Multiresistant strains are virulent since they were incriminated for a 11% death rate. In 60% of amikacin resistant strains AAC (6') I was detected. Among multiresistant strains serotype O:12 predominated. From the hospital pharmacy data, it was evident that antibiotic consumption refers to greater than 60% of hospital admissions, and amikacin, netilmicin and newer cephalosporins are the first line antibiotics. It is evident that urgent changes are needed in the antibiotic policies in the Laiko General Hospital.