Pharmacotherapies for multidrug-resistant gram-positive infections: current options and beyond.

INTRODUCTION: Infections due to multidrug-resistant organisms (MDRO) are a serious concern for public health with high morbidity and mortality. Though many antibiotics have been introduced to manage these infections, there are remaining concerns regarding the optimal management of Gram-positive MDROs. AREAS COVERED: A literature search on the PubMed/Medline database was conducted. We applied no language and time limits for the search strategy. In this narrative review, we discuss the current options for managing Gram-positive MDROs as well as non-traditional antibacterial agents in development. EXPERT OPINION: Despite their introduction more than 70 years ago, glycopeptides are still the cornerstone in treating Gram-positive infections: all registrative studies of new antibiotics have glycopeptides as control; these studies are designed as not inferior studies, therefore it is almost impossible to give recommendations other than the use of glycopeptides in the treatment of Gram-positive infections. The best evidence on treatments different from glycopeptides comes from post-hoc analysis and meta-analysis. Non-traditional antibacterial agents are being studied to aid in short and effective antibiotic therapies. The use of non-traditional antibacterial agents is not restricted to replacing traditional antibacterial agents with alternative therapies; instead, they should be used in combination with antibiotic therapies.

Familial polycystic kidneys with no genetic confirmation: Are we sure it is ADPKD?

Autosomal dominant polycystic kidney disease (ADPKD) is the most common heritable multifocal cystic disease encountered in clinical practice, and it is usually diagnosed in patients with family history by the evidence of markedly enlarged kidneys with multiple bilateral cysts at ultrasound (U.S.), computed tomography (CT) scan, or magnetic resonance imaging (MRI). In most cases, genetic testing is not required. Though ADPKD diagnosis is often straightforward, misdiagnosis is possible. Here we present a case of ADPKD misdiagnosis, followed by a review of the most important kidney heritable multifocal cystic diseases. Our case report demonstrates that ADPKD can be erroneously diagnosed when other kidney heritable multifocal cystic diseases occur without their distinguishing manifestations and when there is no genetic characterization among the relatives. A proper diagnosis of heritable diseases is crucial, as it allows an appropriate management of family members who carry disease allele, apart from patient management. Therefore, we suggest a careful differential diagnosis with possible molecular genetic analysis in presentations with familial cystic kidneys and suspicious clinical and radiological features.

New antimicrobial options for the management of complicated intra-abdominal infections.

Complicated intra-abdominal infections (cIAIs) are a common cause of morbidity and mortality in surgical patients. Optimal management of cIAI requires early source control in combination with adequate antimicrobial treatment and aggressive fluid resuscitation. cIAIs are mainly caused by Gram-negative bacilli and anaerobes. Broad-spectrum single-agent or combination drug regimens against these microorganisms are the mainstay of therapy. However, development of antimicrobial resistance has become an increasingly large concern: multidrug-resistant organisms are associated with a higher rate of inadequate antimicrobial therapy, which in turn is associated with higher mortality rate, longer hospital stay, and increased cost compared to adequate antimicrobial therapy. In this mini-review, we discuss the effectiveness of several new antimicrobial agents, recently approved or in advanced phases of clinical development, for the treatment of cIAIs, including the new beta-lactam and beta-lactamase inhibitor combinations (ceftolozane/tazobactam, ceftazidime/avibactam, meropenem/vaborbactam, imipenem/cilastatin/relebactam, aztreonam/avibactam), siderophore cephalosporins (cefiderocol), aminoglycosides (plazomicin), and tetracyclines (eravacycline).

New antibiotics for the treatment of serious infections in intensive care unit patients.

Objective: Nowadays, the infections of patients admitted to intensive care units (ICUs) are a major public health problem; this is due to several factors, in primis an increase in antibiotic resistance and the inappropriate use of antibiotics. Methods: We briefly focus on on both new antibiotics approved by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) in the last decade (2010-2019), and on agents in an advanced phase of development that have been developed, or are already approved, for the treatment of serious infections due to multidrug-resistant bacteria, both Gram-positive and Gram-negative bacteria. Results: An adequate knowledge of the new antibiotics will reduce their inappropriate use with the consequent reduction in the onset of new resistance and decreasing health care costs. Conclusion: Antimicrobial stewardship programs to optimize antimicrobial prescribing and to preserve the effectiveness of the new antimicrobial agents are urgently needed'.

Retrocardiac pneumonia mimicking acute abdomen: a diagnostic challenge.

We present the case of a child who showed acute abdominal pain and fever due to retrocardiac pneumonia by Streptococcus pneumoniae without respiratory signs and symptoms. Acute abdominal pain is a common presenting symptom of children seen in pediatric emergency rooms. Basilar pneumonia is an uncommonly known cause of pediatric abdominal pain; it may go unrecognized on a patient's initial evaluation. Our case suggests that the clinical manifestations of a retrocardiac pneumonia can be atypical with abdominal pain as the principal complaint, mimicking acute abdomen.

Immunoglobulin therapy of fetal cytomegalovirus infection occurring in the first half of pregnancy--a case-control study of the outcome in children.

BACKGROUND: Primary cytomegalovirus (CMV) infection early in gestation causes severe disease. METHODS: Case patients were 32 congenitally infected children aged 1-5 years who had either hearing deficit and/or psychomotor retardation and whose mothers had a confirmed or probable primary CMV infection at ≤ 20 weeks' gestation. Control subjects were 32 congenitally infected normal children whose mothers had a confirmed primary infection at ≤ 20 weeks' gestation. Case patients and control subjects were matched by the weeks of maternal gestation (± 1 week) at the mother's infection and by the child's age (± 1 year) at evaluation. RESULTS: For the case patients and control subjects, the mean age was 3.0 years. The mean number of weeks of gestation at maternal infection was 11 weeks. The only risk factor for an affected child was the mother not receiving immunoglobulin (P = .001). Of the 32 case patients, only 4 mothers received CMV immunoglobulin, compared with 27 of the 32 mothers of control infants (adjusted odds ratio, 14 [95% confidence interval, 1.7-110]). The rate of both psychomotor retardation and hearing deficit decreased with immunoglobulin. CONCLUSIONS: These results support the efficacy of immunoglobulins for decreasing the severity of disabilities caused by fetal CMV infection after a primary maternal infection during pregnancy.

Non-typhoidal Salmonella septic arthritis in an immunocompetent child with a pharyngeal streptococcal infection.

We report the case of an immunocompetent child who showed monoarticular arthritis and fever, preceded by pharyngitis and arthralgias. Because group A beta-hemolytic Streptococcus had been detected in the pharyngeal swab, erythromycin was given on admission. However, based on ultrasound examination, therapy with ceftriaxone and joint fluid drainage were promptly performed, and a rapid and full recovery followed. Meanwhile, Salmonella enterica infection was revealed in blood and joint fluid. Our case suggests that septic arthritis caused by a non-typhoidal Salmonella infection may occur without gastrointestinal manifestations and concomitantly with a pharyngeal streptococcal infection.