Oguz Resat Sipahi

Economics of antibiotic resistance.

Antibiotics are developed to kill microorganisms; however, microorganisms develop and disseminate resistance as a reaction to antimicrobials in accordance with the laws of evolution and natural selection. Resistant and multidrug-resistant bacterial infections comprise a great problem in both the community and hospital setting. Increasing values of health expenditures, including antibiotics, is a global problem. Antibiotic resistance is not always, but usually, associated with significant morbidity, longer hospitalization, excess costs and mortality. Excess costs associated with resistant microorganisms may be due to: obligation to use more expensive antibiotics, longer hospital stay, higher mortality, delayed appropriate antibiotic therapy or a necessity to perform surgery. Optimal use of existing antimicrobial agents, using alternative treatment options (where possible), reducing the need for antimicrobials by increasing immunity, reducing the use of antimicrobials without providing an alternative form of treatment through education of health professionals and patients, antibiotic policies (including antibiotic stewardship and regulations for restricted use), implementation of infection control measures (e.g., hand washing, screening and isolation) are the strategies aimed at prevention of emergence and spread of antibiotic resistance.

Nitrofurantoin in the treatment of extended-spectrum β-lactamase-producing Escherichia coli-related lower urinary tract infection.

The aim of this study was to evaluate the effect of nitrofurantoin (NFT) in the treatment of extended-spectrum β-lactamase (ESBL)-producing Escherichia coli-related lower urinary tract infection (LUTI). The hospital records of all patients aged >18 years with dysuria or problems with frequency or urgency in passing urine, >20 leukocytes/mm(3) in urine microscopy and culture-proven ESBL-producing NFT-sensitive E. coli in the urine (>10(5) CFU/mm(3)), no leukocytosis or fever and who were treated with NFT between January 2006 and May 2011 in our outpatient clinic or in the hospital were evaluated. All patients had received a NFT 50 mg capsule every 6 h for 14 days and had a control urine culture taken 7-9 days after therapy. Clinical success was defined as resolution of symptoms at the control visit, and microbiological success was defined as a sterile control urine culture. A total of 75 patients (mean±standard deviation age, 54±17 years; 45 females, 30 males, all but 14 with complicated LUTI) fulfilled the study inclusion criteria. Overall clinical and microbiological success rates were 69% (52/75) and 68% (51/75), respectively. Control urine culture performed 28-31 days after the end of therapy was available in 31/51 patients (61%) with microbiological success. Re-infection and relapse rates were 6.5% (2/31) and 3.2% (1/31), respectively. In conclusion, these results suggest that NFT may be an alternative in the treatment of ESBL-producing E. coli-related LUTI. This is the first study in which NFT was used in the treatment of LUTI due to ESBL-producing E. coli as well as in patients with complicated UTI.

Efficacy and Tolerability of Antibiotic Combinations in Neurobrucellosis: Results of the Istanbul Study

ABSTRACT No data on whether brucellar meningitis or meningoencephalitis can be treated with oral antibiotics or whether an intravenous extended-spectrum cephalosporin, namely, ceftriaxone, which does not accumulate in phagocytes, should be added to the regimen exist in the literature. The aim of a study conducted in Istanbul, Turkey, was to compare the efficacy and tolerability of ceftriaxone-based antibiotic treatment regimens with those of an oral treatment protocol in patients with these conditions. This retrospective study enrolled 215 adult patients in 28 health care institutions from four different countries. The first protocol (P1) comprised ceftriaxone, rifampin, and doxycycline. The second protocol (P2) consisted of trimethoprim-sulfamethoxazole, rifampin, and doxycycline. In the third protocol (P3), the patients started with P1 and transferred to P2 when ceftriaxone was stopped. The treatment period was shorter with the regimens which included ceftriaxone (4.40 ± 2.47 months in P1, 6.52 ± 4.15 months in P2, and 5.18 ± 2.27 months in P3) (P = 0.002). In seven patients, therapy was modified due to antibiotic side effects. When these cases were excluded, therapeutic failure did not differ significantly between ceftriaxone-based regimens (n = 5/166, 3.0%) and the oral therapy (n = 4/42, 9.5%) (P = 0.084). The efficacy of the ceftriaxone-based regimens was found to be better (n = 6/166 [3.6%] versus n = 6/42 [14.3%]; P = 0.017) when a composite negative outcome (CNO; relapse plus therapeutic failure) was considered. Accordingly, CNO was greatest in P2 (14.3%, n = 6/42) compared to P1 (2.6%, n = 3/117) and P3 (6.1%, n = 3/49) (P = 0.020). Seemingly, ceftriaxone-based regimens are more successful and require shorter therapy than the oral treatment protocol.

Pooled analysis of 2,408 cases of acute adult purulent meningitis from Turkey.

Objectives: The aim of this study was to systematically review the Turkish literature of acute adult purulent meningitis. Materials and Methods: The published series of three national databases and two international databases were searched to perform the review. In addition to the databases, abstracts of congresses held between 1994 and 2003 by the Turkish Clinical Microbiology and Infectious Diseases Association, Turkish Microbiology Association, and the Antibiotic and Chemotherapy Association were searched for reports about acute purulent meningitis. Results: Data for 2,408 patients with a diagnosis of acute purulent meningitis were obtained from 30 reports. In terms of clinical findings, 1,254 of 1,570 (79.8%) had fever (>38°C), 1,408 of 1,595 (88.2%) headache, 1,403 of 1,562 (89.8%) stiffness of the neck, and 649 of 784 (82.7%) leukocytosis (>10,000/mm3). Cerebrospinal fluid culture yielded a pathogen in 873 of 2,260 (38.6%) patients. The most common pathogen was Streptococcus pneumoniae, followed by Neisseria meningitidis and Staphylococcus aureus. Overall mortality was 425 of 2,408 (17.6%). Pathogen-specific mortality was 60 of 202 (29.7%) for S. pneumoniae and 6 of 100 (6%) for N. meningitidis. Conclusion: Meningitis is a serious, life-threatening disease. More preventive measures should be sought to further decrease the mortality and morbidity related to acute purulent meningitis.

The microbiological diagnosis of tuberculous meningitis: results of Haydarpasa-1 study

We aimed to provide data on the diagnosis of tuberculous meningitis (TBM) in this largest case series ever reported. The Haydarpasa-1 study involved patients with microbiologically confirmed TBM in Albania, Croatia, Denmark, Egypt, France, Hungary, Iraq, Italy, Macedonia, Romania, Serbia, Slovenia, Syria and Turkey between 2000 and 2012. A positive culture, PCR or Ehrlich-Ziehl-Neelsen staining (EZNs) from the cerebrospinal fluid (CSF) was mandatory for inclusion of meningitis patients. A total of 506 TBM patients were included. The sensitivities of the tests were as follows: interferon-γ release assay (Quantiferon TB gold in tube) 90.2%, automated culture systems (ACS) 81.8%, Löwenstein Jensen medium (L-J) 72.7%, adenosine deaminase (ADA) 29.9% and EZNs 27.3%. CSF-ACS was superior to CSF L-J culture and CSF-PCR (p <0.05 for both). Accordingly, CSF L-J culture was superior to CSF-PCR (p <0.05). Combination of L-J and ACS was superior to using these tests alone (p <0.05). There were poor and inverse agreements between EZNs and L-J culture (κ = -0.189); ACS and L-J culture (κ = -0.172) (p <0.05 for both). Fair and inverse agreement was detected for CSF-ADA and CSF-PCR (κ = -0.299, p <0.05). Diagnostic accuracy of TBM was increased when both ACS and L-J cultures were used together. Non-culture tests contributed to TBM diagnosis to a degree. However, due to the delays in the diagnosis with any of the cultures, combined use of non-culture tests appears to contribute early diagnosis. Hence, the diagnostic approach to TBM should be individualized according to the technical capacities of medical institutions particularly in those with poor resources.

Moxifloxacin versus ampicillin + gentamicin in the therapy of experimental Listeria monocytogenes meningitis

OBJECTIVES This study aimed to compare the antibacterial activity of moxifloxacin and ampicillin + gentamicin in the treatment of Listeria monocytogenes meningitis in a rabbit meningitis model. METHODS Meningitis was induced by direct inoculation of a clinical strain isolated from an immunocompromised patient (10(7) cfu/mL) into the cisterna magna of New Zealand rabbits. After 16 h of incubation, rabbits were separated into four groups: moxifloxacin (M), ampicillin + gentamicin (A), ampicillin + gentamicin 2 (A2) and control (C). Group M received 20 mg/kg moxifloxacin at the end of the incubation time and 5 h later by intravenous (i.v.) route. Group A received ampicillin (30 mg/kg/h) and gentamicin (2.5 mg/kg/h) by i.v. route with continuous infusion for 8 h in 36 mL of 0.9% NaCl, group A2 received the same dosage of gentamicin and ampicillin in two different 36 mL 0.9% NaCl solutions and group C did not receive any treatment. Cerebrospinal fluid (CSF) samples (0.1-0.25 mL) were obtained 16 and 24 h after induction of meningitis. RESULTS At the end of the 16 h of incubation, CSF bacterial counts were similar in all groups (P > 0.05). At the final stage of the study (24 h after induction of meningitis), bacterial counts in all treatment groups were significantly lower than the control group (P < 0.05). When the three treatment groups were compared, bacterial counts were found to be similar (P > 0.05). CONCLUSIONS These data suggest that antibacterial activity of moxifloxacin is similar to ampicillin + gentamicin in the treatment of experimental L. monocytogenes meningitis of rabbits.

Results of a Multinational Study Suggest the Need for Rapid Diagnosis and Early Antiviral Treatment at the Onset of Herpetic Meningoencephalitis

ABSTRACT Data in the literature regarding the factors that predict unfavorable outcomes in adult herpetic meningoencephalitis (HME) cases are scarce. We conducted a multicenter study in order to provide insights into the predictors of HME outcomes, with special emphasis on the use and timing of antiviral treatment. Samples from 501 patients with molecular confirmation from cerebrospinal fluid were included from 35 referral centers in 10 countries. Four hundred thirty-eight patients were found to be eligible for the analysis. Overall, 232 (52.9%) patients experienced unfavorable outcomes, 44 died, and 188 survived, with sequelae. Age (odds ratio [OR], 1.04; 95% confidence interval [CI], 1.02 to 1.05), Glasgow Coma Scale score (OR, 0.84; 95% CI, 0.77 to 0.93), and symptomatic periods of 2 to 7 days (OR, 1.80; 95% CI, 1.16 to 2.79) and >7 days (OR, 3.75; 95% CI, 1.72 to 8.15) until the commencement of treatment predicted unfavorable outcomes. The outcome in HME patients is related to a combination of therapeutic and host factors. This study suggests that rapid diagnosis and early administration of antiviral treatment in HME patients are keys to a favorable outcome.

Meningitis Due to Providencia stuartii

ABSTRACT In this report, we present a case of postneurosurgical meningitis due to Providencia stuartii, which was treated successfully with meropenem therapy lasting 21 days.

Linezolid in the treatment of methicillin-resistant staphylococcal post-neurosurgical meningitis: A series of 17 cases

Abstract Background: Linezolid is a bacteriostatic antibiotic with good cerebrospinal fluid penetration. The aim of this study was to evaluate the efficacy of linezolid in methicillin-resistant staphylococcal (methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant coagulase-negative Staphylococcus (MRCoNS)) meningitis. Methods: We extracted data and outcomes for all adult patients (age > 18 y) with culture-proven MRSA or MRCoNS meningitis treated with linezolid between January 2006 and September 2010 in our hospital. Demographic, clinical, and laboratory data and predisposing factors, as well as information on response to treatment and outcome were obtained by regular visits. Results: A total of 17 cases (9 MRCoNS, 7 MRSA, and 1 MRCoNS and MRSA mixed) fulfilled the inclusion criteria. All patients had hospital-acquired meningitis and had undergone neurosurgery. Cumulative microbiological success on day 5 was 88%. There was 1 staphylococcal meningitis-related death. There were no severe adverse events. Conclusions: Our experience with linezolid suggests that it can be an alternative for the treatment of MRCoNS- and MRSA-related meningitis.

Mortality indicators in pneumococcal meningitis: therapeutic implications

BACKGROUND The aim of this study was to delineate mortality indicators in pneumococcal meningitis with special emphasis on therapeutic implications. METHODS This retrospective, multicenter cohort study involved a 15-year period (1998-2012). Culture-positive cases (n=306) were included solely from 38 centers. RESULTS Fifty-eight patients received ceftriaxone plus vancomycin empirically. The rest were given a third-generation cephalosporin alone. Overall, 246 (79.1%) isolates were found to be penicillin-susceptible, 38 (12.2%) strains were penicillin-resistant, and 22 (7.1%) were oxacillin-resistant (without further minimum inhibitory concentration testing for penicillin). Being a critical case (odds ratio (OR) 7.089, 95% confidence interval (CI) 3.230-15.557) and age over 50 years (OR 3.908, 95% CI 1.820-8.390) were independent predictors of mortality, while infection with a penicillin-susceptible isolate (OR 0.441, 95% CI 0.195-0.996) was found to be protective. Empirical vancomycin use did not provide significant benefit (OR 2.159, 95% CI 0.949-4.912). CONCLUSIONS Ceftriaxone alone is not adequate in the management of pneumococcal meningitis due to penicillin-resistant pneumococci, which is a major concern worldwide. Although vancomycin showed a trend towards improving the prognosis of pneumococcal meningitis, significant correlation in statistical terms could not be established in this study. Thus, further studies are needed for the optimization of pneumococcal meningitis treatment.