Valproic acid (VPA) is a commonly prescribed anticonvulsant drug for the treatment of various forms of epilepsy. Concomitant administration of VPA and carbapenem antibiotics such as panipenem/ betamipron and meropenem has been reported to decrease the serum level of VPA. We observed seven cases which showed a decrease in serum levels of VPA due to concomitant use of VPA and carbapenem from January 2002 to October 2006 in a 750-bed university hospital, the average decrease of 70.4% was observed. Carbapenem antibiotics administrated concomitantly with VPA were panipenem (1 case), meropenem (3 cases), and imipenem (2 cases), and in one other case imipenem and meropenem were used sequentially. We found the VPA serum levels were significantly decreased with meropenem (n=4) more than with other carbapenem antibiotics (n=4, 89.3% vs. 51.5% decrease, P=0.03). Clinicians should be aware of this potential interaction, pay attention to the failure of seizure control due to decreased serum VPA levels with concomitant use of carbapenem antibiotics, and monitor VPA serum levels for those cases.
Adult ; Aged ; Aged, 80 and over ; Anti-Bacterial Agents/administration & dosage/*therapeutic use ; Anticonvulsants/administration & dosage/*blood/therapeutic use ; Carbapenems/administration & dosage/*therapeutic use ; Drug Interactions ; Drug Therapy, Combination ; Epilepsy/*drug therapy ; Female ; Humans ; Imipenem/therapeutic use ; Male ; Middle Aged ; Thienamycins/therapeutic use ; Valproic Acid/administration & dosage/*blood/therapeutic use

INTRODUCTIONInstitutional febrile neutropenia (FN) management protocols were changed following the finding of a high prevalence of ceftazidime-resistant Gram-negative bacteraemia (CR-GNB) among haematology patients with FN. Piperacillin/tazobactam replaced ceftazidime as the initial empirical antibiotic of choice, whereas carbapenems were prescribed empirically for patients with recent extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae colonisation/infection. An audit was conducted to determine the impact of these changes.

METHODSData from all FN episodes between October 2008 and December 2010 were collected prospectively, with mid-November 2009 demarking the transition between pre-intervention and intervention periods. Outcomes measured included 30-day mortality post-development of FN and the presence of CR-GNB.

RESULTSThere were 427 FN episodes (200 in the pre-intervention period) from 225 patients. The prevalence of CRGNB was 10.3%, while the 30-day mortality was 4.7%, with no difference between pre-intervention and intervention periods. Independent risk factors for 30-day mortality included the presence of active haematological disease, vancomycin prescription and older age. Independent factors associated with initial CR-GNB were profound neutropenia, the presence of severe sepsis and active haematological disease. Recent ESBL-producing Enterobacteriaceae colonisation/infection was not predictive of subsequent CR-GNB (positive predictive value 17.3%), whereas a model based on independent risk factors had better negative predictive value (95.4%) but similarly poor positive predictive value (21.4%), despite higher sensitivity.

CONCLUSIONA change in the FN protocol did not result in improved outcomes. Nonetheless, the audit highlighted that empirical carbapenem prescription may be unnecessary in FN episodes without evidence of severe sepsis or septic shock, regardless of previous microbiology results.

Academic Medical Centers ; Adult ; Bacteremia ; complications ; drug therapy ; Carbapenems ; therapeutic use ; Ceftazidime ; pharmacology ; Drug Resistance, Multiple ; Febrile Neutropenia ; complications ; drug therapy ; Female ; Gram-Negative Bacteria ; Humans ; Male ; Middle Aged ; Penicillanic Acid ; administration & dosage ; analogs & derivatives ; Piperacillin ; administration & dosage ; Prevalence ; Prospective Studies ; Risk Factors ; Sepsis ; Singapore ; Treatment Outcome ; Universities

IN the presence of septic shock, every hour in delaying the administration of effective antibiotics is associated with a measurable increase in mortality. This is especially true for neutropenic patients with septic shock.1 As there is a higher incidence of involving multi-drug resistant pathogens for neutropenic patients, the decision on antibiotics regime remains a challenge for physicians.2 Immunosuppression and previous antibacterial use are factors that promote the spread of multi-drug resistant pathogens, and the possibility of co-existing multi-drug resistant pathogens should be suspected when treating patients with these risk factors who developed refractory shock. Here we present a case with neutropenic fever and refractory shock whose blood culture yielded multi-drug resistant Acinetobacter baumannii and carbapenem- resistant Klebsiella pneumoniae.
Acinetobacter Infections ; blood ; drug therapy ; microbiology ; Acinetobacter baumannii ; drug effects ; isolation & purification ; Adult ; Bacteremia ; blood ; drug therapy ; microbiology ; Carbapenems ; administration & dosage ; pharmacology ; therapeutic use ; Drug Resistance, Multiple, Bacterial ; Fatal Outcome ; Humans ; Klebsiella Infections ; blood ; drug therapy ; microbiology ; Klebsiella pneumoniae ; drug effects ; isolation & purification ; Male ; Shock, Septic ; blood ; drug therapy ; microbiology

BACKGROUND: Acinetobacter baumannii has emerged as a major cause of nosocomial outbreaks. It is particularly associated with nosocomial pneumonia and bloodstream infections in immunocompromised and debilitated patients with serious underlying pathologies. Over the last two decades, a remarkable rise in the rates of multidrug resistance to most antimicrobial agents that are active against A. baumannii has been noted worldwide. We evaluated the rates of antimicrobial resistance and changes in resistance over a 5-year period (2010–2014) in A. baumannii strains isolated from hospitalized patients in a tertiary Greek hospital. MATERIALS AND METHODS: Identification of A. baumannii was performed by standard biochemical methods and the Vitek 2 automated system, which was also used for susceptibility testing against 18 antibiotics: ampicillin/sulbactam, ticarcillin, ticarcillin/clavulanic acid, piperacillin, piperacillin/tazobactam, cefotaxime, ceftazidime, cefepime, imipenem, meropenem, gentamicin, amikacin, tobramycin, ciprofloxacin, tetracycline, tigecycline, trimethoprim/sulfamethoxazole, and colistin. Interpretation of susceptibility results was based on the Clinical and Laboratory Standards Institute criteria, except for tigecycline, for which the Food and Drug Administration breakpoints were applied. Multidrug resistance was defined as resistance to ≥3 classes of antimicrobial agents. RESULTS: Overall 914 clinical isolates of A. baumannii were recovered from the intensive care unit (ICU) (n = 493), and medical (n = 252) and surgical (n = 169) wards. Only 4.9% of these isolates were fully susceptible to the antimicrobials tested, while 92.89% of them were multidrug resistant (MDR), i.e., resistant to ≥3 classes of antibiotics. ICU isolates were the most resistant followed by isolates from surgical and medical wards. The most effective antimicrobial agents were, in descending order: colistin, amikacin, trimethoprim/sulfamethoxazole, tigecycline, and tobramycin. Nevertheless, with the exception of colistin, no antibiotic was associated with a susceptibility rate >40% for the entire study period. The most common phenotype showed resistance against ampicillin/sulbactam, cephalosporins, carbapenems, aminoglycosides, ciprofloxacin, and tigecycline. An extremely concerning increase in colistin-resistant isolates (7.9%) was noted in 2014, the most recent study year. CONCLUSION: The vast majority of A. baumannii clinical isolates in our hospital are MDR. The remaining therapeutic options for critically ill patients who suffer from MDR A. baumannii infections are severely limited, with A. baumannii beginning to develop resistance even against colistin. Scrupulous application of infection control practices should be implemented in every hospital unit. Lastly, given the lack of available therapeutic options for MDR A. baumannii infections, well-controlled clinical trials of combinations of existing antibiotics are clearly needed.
Acinetobacter baumannii* ; Acinetobacter* ; Amikacin ; Aminoglycosides ; Anti-Bacterial Agents ; Anti-Infective Agents ; Carbapenems ; Cefotaxime ; Ceftazidime ; Cephalosporins ; Ciprofloxacin ; Colistin ; Critical Illness ; Disease Outbreaks ; Drug Resistance, Multiple ; Gentamicins ; Hospital Units ; Humans ; Imipenem ; Infection Control ; Intensive Care Units ; Pathology ; Phenotype ; Piperacillin ; Pneumonia ; Tetracycline ; Ticarcillin ; Tobramycin ; United States Food and Drug Administration