Ceftazidime/avibactam in the era of carbapenemase-producing Klebsiella pneumoniae: experience from a national registry study.

BACKGROUND: Infections caused by KPC-producing Klebsiella pneumoniae (Kp) are associated with high mortality. Therefore, new treatment options are urgently required. OBJECTIVES: To assess the outcomes and predictors of mortality in patients with KPC- or OXA-48-Kp infections treated with ceftazidime/avibactam with an emphasis on KPC-Kp bloodstream infections (BSIs). METHODS: A multicentre prospective observational study was conducted between January 2018 and March 2019. Patients with KPC- or OXA-48-Kp infections treated with ceftazidime/avibactam were included in the analysis. The subgroup of patients with KPC-Kp BSIs treated with ceftazidime/avibactam was matched by propensity score with a cohort of patients whose KPC-Kp BSIs had been treated with agents other than ceftazidime/avibactam with in vitro activity. RESULTS: One hundred and forty-seven patients were identified; 140 were infected with KPC producers and 7 with OXA-48 producers. For targeted therapy, 68 (46.3%) patients received monotherapy with ceftazidime/avibactam and 79 (53.7%) patients received ceftazidime/avibactam in combination with at least another active agent. The 14 and 28 day mortality rates were 9% and 20%, respectively. The 28 day mortality among the 71 patients with KPC-Kp BSIs treated with ceftazidime/avibactam was significantly lower than that observed in the 71 matched patients, whose KPC-Kp BSIs had been treated with agents other than ceftazidime/avibactam (18.3% versus 40.8%; P = 0.005). In the Cox proportional hazards model, ultimately fatal disease, rapidly fatal disease and Charlson comorbidity index ≥2 were independent predictors of death, whereas treatment with ceftazidime/avibactam-containing regimens was the only independent predictor of survival. CONCLUSIONS: Ceftazidime/avibactam appears to be an effective treatment against serious infections caused by KPC-Kp.

Double-carbapenem combination as salvage therapy for untreatable infections by KPC-2-producing Klebsiella pneumoniae.

We report our experience using the double-carbapenem combination as salvage therapy for patients with untreatable infections caused by KPC-2- producing Klebsiella pneumoniae. A total of 27 patients in two institutions in Athens, Greece suffering from complicated urinary tract infections (16) with or without secondary bacteraemia (four and 12 respectively), primary (six) or catheter-related bloodstream infections (two), HAP or VAP (two) and external ventricular drainage infection (one) were treated exclusively with ertapenem and high-dose prolonged infusion meropenem because in-vitro active antimicrobials were unavailable (19) or failed (four) or were contraindicated (six). Most patients presented with severe infections with median APACHE II score of 17 and 11 of those patients (40.7%) had severe sepsis (five) or septic shock (six). The clinical and microbiological success was 77.8 and 74.1% respectively. Crude mortality was 29.6% with attributable mortality of 11.1%. Adverse events, none of them severe, were reported in four patients (14.8%). The double-carbapenem combination as an exclusive regimen represents a safe and valid salvage therapy for untreatable infections by extensively- or pandrug-resistant KPC-producing K.pneumoniae.

Antiviral drugs in the prophylaxis of HBV infection.

Reactivation of hepatitis B infection (HBV) is known to occur in liver graft recipients and in chronic carriers of the surface antigen of HBV who receive immunosuppressive therapy. The use of hepatitis B immune globulin alone or in combination with antiviral agents such as lamivudine, adefovir, tenofovir, entecavir, famciclovir, ganciclovir, as prophylaxis in HBV liver transplants, has been well documented. In terms of HBV positive carriers undergoing cytotoxic chemotherapy, the preemptive use of nucleoside or nucleotide analogues seems to be effective. Monotherapy or combination of antiviral drugs, as well as the optimal duration of HBV prophylaxis, is to be determined.

Recent advances in the treatment of HIV/HBV and HIV/HCV co-infection.

Concurrent infection with hepatitis B virus (HBV) and hepatitis C virus (HCV) in patients positive for human immunodeficiency virus (HIV) is relatively common. The treatment of co-infected individuals is rather complex because the anti-viral therapy may be associated with drug-resistance, hepatotoxicity and lack of response. Herein, we present a summary of the available compounds and the recent recommendations concerning the therapeutic management of HIV/HBV and HIV/HCV co-infections.

Cytokine gene polymorphisms in multiple sclerosis: a meta-analysis of 45 studies including 7379 cases and 8131 controls.

Many environmental and genetic factors have been implicated in the development of multiple sclerosis. However, the aetiology has not been clarified yet. Therefore, using a meta-analytic approach, we tried to probe the potential association between various cytokine gene polymorphisms and the occurrence of multiple sclerosis. A comprehensive literature search yielded 45 eligible studies, which involved 7379 cases and 8131 controls. Totally, the effect of eight polymorphisms, i.e. IL-1A C[-889]T, IL-1B C[-511]T, IL-1B C[3953]T, IL-4 C[33]T, IL-10 C[-819]T, IL-10 G[-1082]A, tumour necrosis factor-a (TNFA) G[-308]A and TNFA G[-238]A, was evaluated in a random-effects meta-analysis. There was no evidence of statistically significant association between the aforementioned polymorphisms and multiple sclerosis. Publication bias and heterogeneity were absent in most analyses. Within its limitations, the current literature-based meta-analysis does not indicate that specific polymorphic variations of genes encoding pro-inflammatory and anti-inflammatory cytokines affect susceptibility to multiple sclerosis.

Assessing the secular trends in the transmission of HIV in Greece.

OBJECTIVE: To evaluate the current trends in HIV transmission in Greece. METHODS: A retrospective study of HIV infected individuals reported to the Hellenic Center for Infectious Diseases Control (HCIDC) was conducted. RESULTS: Since the beginning of the epidemic in Greece and until early 1990s most cases concerned men who have sex with men (MSM). After the mid-1990s the proportion of homosexual males among HIV positive individuals decreased slightly, then was stabilised but they still remain the dominant population among HIV positive people. On the other hand, heterosexual transmission increased steadily and has become a frequent route for the spread of HIV/AIDS in recent years. Individuals originating from or travelling to countries where this mode of transmission prevails were the most frequent cases in this category. A significant proportion of cases classified as "undetermined" were also recorded and were partially attributed to the increased heterosexual transmission among people (especially women) without obvious high risk behaviours. CONCLUSIONS: The HIV/AIDS surveillance system must evolve in order to find the new unreported risk information and identify the population groups at higher risk. This will help to implement preventive policies and information campaigns addressed to target populations with special attention paid to immigrants, women, and marginalized communities.

Surveillance data on paediatric HIV infection and AIDS in Greece.

In Greece, HIV/AIDS surveillance is conducted by the Hellenic Centre for Infectious Diseases Control. The AIDS case reporting system was implemented in 1984, followed by notification of HIV infections in 1998. This article presents surveillance and trend analysis of paediatric HIV infection and AIDS, including cases identified prior to 1998. The number of HIV infected children in Greece is relatively low, raising to a cumulative total of 69 cases by June 2003, 44 (64%) of whom are thought to have been infected through mother-to-child transmission. Thirty three paediatric AIDS cases have been reported since the onset of epidemic, with Pneumonocystis carinii pneumonia being the most frequent opportunistic infection. A significant number of children in Greece were diagnosed after the age of 1 year. This could be attributed to the fact that many HIV-infected women are not identified during pregnancy, despite that fact that voluntary testing is available. It could also be attributed to the fact that data includes HIV infections collected retrospectively after 1998, and that foreign HIV-infected children may arrive in Greece at a later age. Furthermore, new paediatric HIV positive cases that were reported during the first half-year period of 2003 were foreign children born in eastern Europe and sub-Saharan Africa. Efforts should be made to identify women in these populations in time for proper intervention. HIV infection in children remains a huge problem worldwide, and it is very important to focus on reducing the risk of mother-to-child transmission.

Epidemiology of aids defining conditions in Greece.

OBJECTIVE: To examine the secular trends of all AIDS opportunistic infections to occur first (OIs) in Greece, by year, by gender and by mode of transmission. METHODS: The study included all AIDS defining conditions reported among Greek residents diagnosed with AIDS from 1981 to June 2003 and notified to the Hellenic Centre of Infectious Diseases Control. The analysis of trends in AIDS defining conditions in Greece has been performed only for the period 1993--2003. RESULTS: From 1981 to the first six months of 2003, 2,394 AIDS cases, 2,361 adults and 33 children, have been reported. HIV wasting syndrome was the most frequent OI to occur first followed by PCP pneumonia and Kaposi sarcoma. The frequency at which OIs occurred first varied by sex. Kaposi sarcoma was more frequent in males while tuberculosis and oesophageal candidiasis were more frequent in females. The frequency at which OIs occurred first varied also by exposure mode. Kaposi sarcoma was more frequent among men who have sex with men but that was not the case for the remaining transmission categories. From 1993 to the first six months of 2003 a downward trend was noticed only for chronic simplex disease. Since the introduction of HAART, an increasing trend was noticed for CMV disease, recurrent pneumonia, oesophageal candidiasis, Burkitt and immunoblastic lymphoma. CONCLUSION: Further epidemiological studies are needed to assess the OIs trends in coming years in order to plan prevention strategies and future medical care needs.